Current treatment strategies for the treatment of brain tumor have been hindered primarily by the... more Current treatment strategies for the treatment of brain tumor have been hindered primarily by the presence of highly lipophilic insurmountable blood-brain barrier (BBB). The purpose of current research was to investigate the efficiency of engineered biocompatible polymeric nanoparticles (NPs) as drug delivery vehicle to bypass the BBB and enhance biopharmaceutical attributes of anti-metabolite methotrexate (MTX) encapsulated NPs. The NPs were prepared by solvent diffusion method using cationic bovine serum albumin (CBA), and characterized for physicochemical parameters such as particle size, polydispersity index, and zeta-potential; while the surface modification was confirmed by FTIR, and NMR spectroscopy. Developed NPs exhibited zestful relocation of FITC tagged NPs across BBB in albino rats. Further, hemolytic studies confirmed them to be non-toxic and biocompatible as compared to free MTX. In vitro cytotoxicity assay of our engineered NPs on HNGC1 tumor cells proved superior uptake in tumor cells; and elicited potent cytotoxic effect as compared to plain NPs and free MTX solution. The outcomes of the study evidently indicate the prospective of CBA conjugated poly (D,L-lactide-co-glycolide) (PLGA) NPs loaded with MTX in brain cancer bomber with amplified capability to circumvent BBB.
Application of analytical chemistry involves a range of techniques and methodologies so as to obt... more Application of analytical chemistry involves a range of techniques and methodologies so as to obtain and appraise the qualitative, quantitative and structural information about the nature of matter. The gathering and interpretation of qualitative, quantitative and structural information seems to be important in many aspects of human endeavor for example manufacturing industries employ analytical data to assess the quality of raw materials, intermediates and finished products. Chromatography is a fundamental separation technique and mostly used in chemical analysis. Nevertheless, to a confined era, it is also used for preparative purposes, particularly for the small amounts of extracted materials that have relatively high intrinsic value. Chromatography is the most persuasive and versatile technique which readily convenient and available to the modern analyst. It can separate a mixture containing several components into its individual one within a single step process and concomitantly give a quantitative estimate of every constituent present in the mixture. Samples may be liquid, gaseous or solid in nature and can be mixture of complexity from a simple blending of two enantiomers to a multi component mixture that may contain variety of different chemical compounds. But nowadays high performance
The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose a... more The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid−polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL was calculated as 85−90% and 10−12%, respectively. The coumarin-6 LPHNP formulations showed rapid internalization within 2 h incubation with MCF-7 and MDA-MB-231 cells. With 8−10 times, greater bioavailability of drug-loaded LPHNPs than free MTX and ACL was obtained. Also, antitumor efficacy of MTX-and ACL-loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse model. This model showed better control over tumor growth with MTX-and ACL-loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs showed prophylactic and anticancer activity in DMBA-induced mouse model at higher dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when administered in combination with MTX. In conclusion, ACL enhances the therapeutic and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs, as confirmed by cell viability and serum angiogenesis (IL-6, TNF-α, IL-1β, COX2, and MMP1) at both transcript and proteome level.
β-Carotene is a red-orange pigment, a known source of vitamin A and has exceptional antioxidant a... more β-Carotene is a red-orange pigment, a known source of vitamin A and has exceptional antioxidant and free radical scavenging potential. However, uses of β-carotene in food industry are inadequate mostly because of their poor water solubility and low stability. Using the complex coacervation technique, the work is meant to fabricate the microcapsules of β-carotene, to examine the physicochemical properties of microcapsules and finally to evaluate the extent of stability improvement. The configuration of electrostatic complexes between whey protein isolate (WPI) and gum acacia (Acacia arabica, GA) was optimized as a function of pH, ionic strength, WPI/GA ratio, core material load and size of final micromolecules. The optimum process conditions were balanced by the ratio of wall materials WPI/GA 2.0/1.0 % and pH value 4.2. Morphological observations showed that microcapsules presented spherical shape, and smooth and continuous surface. The effective amount of encapsulated core was greater than 70 % for all formulations evaluated. In vitro release data indicated an initial burst release followed by sustained release behavior. The microstructure and viscoelastic properties of WPI and GA complex were studied using dynamic rheometer. The encapsulation method and the wall materials used in this work gave effective protection during storage and eventually resulted sustained release of bioactive while used in food matrix, at suitable conditions.
The purpose of the present study was to investigate the tumor targeting potential of surface tail... more The purpose of the present study was to investigate the tumor targeting potential of surface tailored solid lipid nanoparticles (SLNs) loaded with an anti-cancer drug doxorubicin HCl (DOX). DOX encapsulating SLNs were prepared, characterized and further mannosylated. The developed formulations were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle size/ polydispersity index and zeta-potential analysis. The formulations were evaluated for in vitro drug release and hemolytic toxicity. The ex vivo cytotoxicity and cellular uptake studies were performed on A549 cell lines. In vivo studies were conducted to determine pharmacokinetics, tissue distribution pattern and nephrotoxic/ hepatotoxic effect of mannosylated SLNs. In vitro, the formulations exhibited a biphasic pattern characterized by initial rapid release of the drug followed by rather slow and prolonged release. Further, the in vitro studies depicted mannose-conjugated SLNs to be least hemolytic and suitable for sustained drug delivery. Mannosylated SLNs were most cytotoxic and were preferably taken up A549 tumor cells as evaluated against uncoated SLNs and plain DOX. Pharmacokinetic studies revealed improved bioavailability, half life and mean residence time of DOX upon mannose conjugation. The biodistribution pattern exhibited that mannosylated SLNs were able to deliver a higher concentration of DOX in the tumor mass. They were also proficient to circumvent damage to renal as well as hepatic tissues. It may therefore be interpreted that mannosylated SLNs are capable to ferry bioactives selectively and specifically to the tumor sites with the interception of minimal side effects, thereby suggesting their potential application in cancer chemotherapy.
Many novel techniques of extraction such as solvent extraction by soxhlet, ultrasonication and ex... more Many novel techniques of extraction such as solvent extraction by soxhlet, ultrasonication and extraction by boiling of licorice have been well developed. But ultrasonication has been proved as the best and relevant method for extraction of the glycyrrhizin. To optimize the process conditions for the maximum yield of the glycyrrhizin and easier purification, three types of solvents were employed such as water; methanol and ethanol coded as G-1, G-2 and G-3 and extraction was carried out at different time (45, 60 and 120 min). Maximum amount of glycyrrhizin was recovered from licorice roots at 45 °C for 45 min of extraction time, yielded good amount of glycyrrhizin 36.46 ± 1.29 % using water as solvent. In the present work TLC method assessed the purity of the extracted dried sample compared to the licorice standard. The FTIR spectra of the present study indicated that the control/standard of glycyrrhizin was exactly in resemblance with G-1 spectra. The phytochemical screening of extracted glycyrrhizin was conducted which indicated the presence of saponins, flavonoids, steroids and absence of carbohydrate sugars, alkaloids, tannins and proteins in G-1. The glycyrrhizin extracted using different solvents has shown effective antibacterial action on all six microorganism. The antioxidant activity of each sample was determined using DPPH and ABTS scavenging assay. The presence of flavonoids in the plants is likely to be responsible for the free radical scavenging effects observed. Although, it was found that G-1 attained maximum free radical scavenging ability against reactive oxygen species (ROS).
Spirulina platensis, planktonic blue-green algae, has been used as a source of protein (60-70%) a... more Spirulina platensis, planktonic blue-green algae, has been used as a source of protein (60-70%) and vitamin supplement for more than 15 years without any unknown adverse events. Traditionally, Spirulina platensis has been used as an antioxidant agent. However, no pharmacological work has been done to evaluate the anti-anxiety activity. The present study was premeditated for the evaluation of the anti-anxiety activity of Spirulina platensis. Elevated plus maze (EPM) and light-dark models were used to evaluate the anti-anxiety potential of Spirulina platensis in Swiss albino mice. Albino mice were treated orally with diverse doses of the Spirulina platensis (i.e. 300 and 400 mg/kg). Diazepam (2 mg/kg, IP) was used as a standard drug. In conclusion, 400 mg/kg dose of Spirulina platensis showed a significant anti anxiety activity (P<0.05) while control group was near to standard group. It concludes that Spirulina platensis could be useful as an anti-anxiety agent for future prospects.
Spirulina Platensis is a blue-green alga that widely used as a food supplement over worldwide. Tw... more Spirulina Platensis is a blue-green alga that widely used as a food supplement over worldwide. Two models were used to study the effects of Spirulina Platensis on nociception which was induced by acetic acid (Writhing test), formalin (Paw licking test). Spirulina Platensis was administered in the dose range of 200 and 400 mg/kg orally 1 h prior to pain induction. Spirulina Platensis contains β-carotene and biliproteins (phycocyanin and biliphycocyanin). Oral administration of Spirulina Platensis revealed dose-dependent antinociceptive effect in all the models for antinociception and it blocked both the neurogenic and inflammatory pain and the nociceptive activity was comparable with the reference drug. The results indicate that 400 mg/kg dose of Spirulina Platensis showed significant antinociceptive activity. The activity can be related with the significant biliprotein such as phycocyanin and biliphycocyanin that have potent anti-oxidant activity.
Highlight Microencapsulation of lycopene was carried out by coacervation method. Casein and G... more Highlight Microencapsulation of lycopene was carried out by coacervation method. Casein and Gum tragacanth was used as coating material. The microencapsules fabricated at 1:2 of Gt:Cas were also revealed the highest loading capacity and maximum coacervates yield Cumulative lycopene release was estimated 86.34±2.69% from microencapsulated formulations at the end of 24 th hr The stability of lycopene in that formulation in term of % residual content were studied for three months.
The present investigation reports the preparation, optimization, and characterization of surface ... more The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 ± 2.40 nm, PDI 0.307 ± 0.004, entrapment efficiency 72.3 ± 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy.
The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanopar... more The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC 50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.
The current work entails a novel strategy of formulating the microparticles of lycopene solely us... more The current work entails a novel strategy of formulating the microparticles of lycopene solely using rational blends of biopolymers without using equipment-intensive techniques. The study is intended to enhance oral bioavailability of lycopene by controlling its release from micro-formulation and facilitating its absorption though lymphatic pathways. Considering the minimum particle size, maximum entrapment efficiency and loading capacity, the amounts of casein (i.e., protein) and gum tragacanth (i.e., polysaccharide) were selected as the critical factors for formulation of microparticles. Complex formation and electrostatic interaction was confirmed by Fourier transform infra red (FTIR) spectra. Size and surface properties of microparticles were studied using scanning electron microscopy (SEM). The optimized formulation (mean particle size: ∼130 m; % entrapment efficiency: ∼67% and loading capacity: ∼71%) designated noticeable improvement in lycopene release profile (over 80% in 24 h). Increment in the values of C max (2.22-fold) and AUC (1.97-fold) further indicated noteworthy augmentation in the rate and extent of bioavailability by the microparticles formulation compared to plain lycopene. The resulting formulation was found to be quite stable all through two months of study episode. The resultant microparticles formulation was evaluated for antioxidant activity and tested for their effectiveness in self life enhancement of vegetable oil by calculating peroxide value under temperature and storage condition. Encapsulation strongly increased the stability of micronutrients. The current investigations, therefore, report the successful development of biopolymeric microparticles with improved bioavailability potential of lycopene.
Out of many complications two major problems facing in formulation industry are poor solubility a... more Out of many complications two major problems facing in formulation industry are poor solubility and short half-life of drugs which results into poor bioavailability after oral administration. Solid dosage forms are coated for a number of reasons, the most important of which is controlling the release profiles and bioavailability of the active ingredient. Thus the development of a significant dissolution procedure for drug products with limited water solubility has been a challenge to the pharmaceutical industry. Aceclofenac (Biopharmaceutical classification Class II drug) is a novel non-steroidal antiinflammatory drugs (NSAIDs) having anti-inflammatory and analgesic properties, and is widely used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The investigation revealed that there is no official dissolution medium available in the literature. The objective of present study is to formulate film coated tablet of Aceclofenac and Chlorzoxazone having short half-life by coating with hydroxyl propyl methyl cellulose (E5 LV). Then the formulated tablets were evaluated for its physicochemical properties and in vitro release studies. The incorporation of drugs into polymer matrices is considered a valid tool in order to optimize insufficient features of the drug molecule, like solubility, stability or toxic effects. In the present work, the incorporation of aceclofenac was performed in inert HPMC and there was no chemical interaction between the drug and polymers as concluded from the FTIR studies. In the present study, parameters such as solubility, medium pH, surfactant type, dissolution behavior of formulations, stability, and discriminatory effect of dissolution testing in different dissolution mediums were studied for the selection of a proper dissolution medium. The drug showed an enhanced release rate in the dissolution media containing pH 6.8 phosphate buffer, 900 ml with 0.5 % sodium lauryl sulphate at 75 rpm for 60 min and thus was chosen as the discriminating dissolution method for film coated aceclofenac formulation. It was found that greater than 80 % of the label amount is released over 60 min.
In the last couple of decades antioxidant agents have entered the health market as an easy and at... more In the last couple of decades antioxidant agents have entered the health market as an easy and attractive means of managing diseases. These agents are of enormous interest for an increasingly health-concerned society, and may be particularly relevant for prophylaxis of a number of diseases i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Antioxidants are also favorable to vascular healthiness and symbolize useful compounds because they are able to diminish overall cardiovascular risk by acting analogous to first line therapy or as adjuvants in case of failure or in situations where first line therapy cannot be used. Furthermore, well-designed trials are indeed needed to improve the therapeutic efficacy and health benefits of antioxidants. Numerous in vivo proof-of-concepts studies are offered to underline the feasibility of nanostructure system in order to optimizing the delivery of cardiovascular drugs. The present review highlights the recent approaches for management of cardiovascular disease using different vesicular and particulate carriers, including liposomes, nanoparticles, and nanoemulsions, with a primary emphasis on those which are expected to enhance the antioxidants level.
Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, ... more Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, initial protein to polysaccharide mixing ratio (Pr:Ps), total biopolymer concentration, core material load and ionic strength. This study is aimed at understanding how these parameters influence the coacervation kinetics, the coacervate yield, and entrapment efficiency. At a Pr:Ps = 2:1, an optimum pH of complex coacervation was found 4.35, at which the intensity of electrostatic interaction was maximum. At these conditions, the phase separation occurred the fastest and the final coacervate yield and entrapment efficiency were the largest. Moreover, the developed -carotene loaded microcapsules formulation was found to have particle size 159.71 ± 2.16 m, coacervates yield 82.51 ± 0.412%, entrapment efficiency 79.36 ± 0.541%. Varying the Pr:Ps shifted the value of optimum pH. Electrostatic interaction and formation of coacervates was confirmed by Fourier Transform Infra Red (FTIR) spectra. Size and surface properties of coacervates were studied using Scanning Electron Microscopy (SEM). Entrapment of core material within the coacervates was confirmed by Confocal Laser Scanning Microscope (CLSM). The resultant formulation was evaluated for release study and antioxidant activity. Stability of encapsulated -carotene was evaluated under three levels of temperature (5, 25 and 40 • C) for 3 months. Encapsulation strongly increased the stability of micronutrients. Our results advocate potential of microcapsules as a novel carrier for the safeguard and sustained release of micronutrient.
The objective of present study was to enhance permeation of bioactive molecules across blood brai... more The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats t...
Salient features such as controlled release, target ability, potential of penetration, improved p... more Salient features such as controlled release, target ability, potential of penetration, improved physical stability, low cost compared to phospholipids, and ease of scaling-up makes solid lipid nanoparticles (SLNs) a viable alternative to liposomes for effective drug delivery. Adapalene (ADA) is a second generation retinoid effective in treating various dermatologic disorders such as Acne vulgaris with a few noticeable dose-mediated side effects. The present study was aimed at developing and characterizing ADA loaded SLNs for effective topical delivery. The formulated SLN system was characterized for particle size, poly dispersity index, entrapment efficiency and drug release properties. The resultant formulation (ADA loaded SLNs incorporated into carbopol hydrogel) was evaluated for in vitro drug release, skin permeation and bio-distribution, rheological behaviour, and texture profile analysis. The SLNs based ADA gel has shown its potential in targeting skin epidermal layer, and reducing systemic penetration. The developed system can avoid systemic uptake of ADA in skin layers, and can localize drug in skin epidermis as confirmed by rat skin model. Our results advocate potential of SLNs as a novel carrier for topical delivery of ADA in topical therapeutic approaches. This study open new avenues for drug delivery which better meets the need of anti-acne research.
Current treatment strategies for the treatment of brain tumor have been hindered primarily by the... more Current treatment strategies for the treatment of brain tumor have been hindered primarily by the presence of highly lipophilic insurmountable blood-brain barrier (BBB). The purpose of current research was to investigate the efficiency of engineered biocompatible polymeric nanoparticles (NPs) as drug delivery vehicle to bypass the BBB and enhance biopharmaceutical attributes of anti-metabolite methotrexate (MTX) encapsulated NPs. The NPs were prepared by solvent diffusion method using cationic bovine serum albumin (CBA), and characterized for physicochemical parameters such as particle size, polydispersity index, and zeta-potential; while the surface modification was confirmed by FTIR, and NMR spectroscopy. Developed NPs exhibited zestful relocation of FITC tagged NPs across BBB in albino rats. Further, hemolytic studies confirmed them to be non-toxic and biocompatible as compared to free MTX. In vitro cytotoxicity assay of our engineered NPs on HNGC1 tumor cells proved superior uptake in tumor cells; and elicited potent cytotoxic effect as compared to plain NPs and free MTX solution. The outcomes of the study evidently indicate the prospective of CBA conjugated poly (D,L-lactide-co-glycolide) (PLGA) NPs loaded with MTX in brain cancer bomber with amplified capability to circumvent BBB.
Application of analytical chemistry involves a range of techniques and methodologies so as to obt... more Application of analytical chemistry involves a range of techniques and methodologies so as to obtain and appraise the qualitative, quantitative and structural information about the nature of matter. The gathering and interpretation of qualitative, quantitative and structural information seems to be important in many aspects of human endeavor for example manufacturing industries employ analytical data to assess the quality of raw materials, intermediates and finished products. Chromatography is a fundamental separation technique and mostly used in chemical analysis. Nevertheless, to a confined era, it is also used for preparative purposes, particularly for the small amounts of extracted materials that have relatively high intrinsic value. Chromatography is the most persuasive and versatile technique which readily convenient and available to the modern analyst. It can separate a mixture containing several components into its individual one within a single step process and concomitantly give a quantitative estimate of every constituent present in the mixture. Samples may be liquid, gaseous or solid in nature and can be mixture of complexity from a simple blending of two enantiomers to a multi component mixture that may contain variety of different chemical compounds. But nowadays high performance
The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose a... more The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid−polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL was calculated as 85−90% and 10−12%, respectively. The coumarin-6 LPHNP formulations showed rapid internalization within 2 h incubation with MCF-7 and MDA-MB-231 cells. With 8−10 times, greater bioavailability of drug-loaded LPHNPs than free MTX and ACL was obtained. Also, antitumor efficacy of MTX-and ACL-loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse model. This model showed better control over tumor growth with MTX-and ACL-loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs showed prophylactic and anticancer activity in DMBA-induced mouse model at higher dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when administered in combination with MTX. In conclusion, ACL enhances the therapeutic and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs, as confirmed by cell viability and serum angiogenesis (IL-6, TNF-α, IL-1β, COX2, and MMP1) at both transcript and proteome level.
β-Carotene is a red-orange pigment, a known source of vitamin A and has exceptional antioxidant a... more β-Carotene is a red-orange pigment, a known source of vitamin A and has exceptional antioxidant and free radical scavenging potential. However, uses of β-carotene in food industry are inadequate mostly because of their poor water solubility and low stability. Using the complex coacervation technique, the work is meant to fabricate the microcapsules of β-carotene, to examine the physicochemical properties of microcapsules and finally to evaluate the extent of stability improvement. The configuration of electrostatic complexes between whey protein isolate (WPI) and gum acacia (Acacia arabica, GA) was optimized as a function of pH, ionic strength, WPI/GA ratio, core material load and size of final micromolecules. The optimum process conditions were balanced by the ratio of wall materials WPI/GA 2.0/1.0 % and pH value 4.2. Morphological observations showed that microcapsules presented spherical shape, and smooth and continuous surface. The effective amount of encapsulated core was greater than 70 % for all formulations evaluated. In vitro release data indicated an initial burst release followed by sustained release behavior. The microstructure and viscoelastic properties of WPI and GA complex were studied using dynamic rheometer. The encapsulation method and the wall materials used in this work gave effective protection during storage and eventually resulted sustained release of bioactive while used in food matrix, at suitable conditions.
The purpose of the present study was to investigate the tumor targeting potential of surface tail... more The purpose of the present study was to investigate the tumor targeting potential of surface tailored solid lipid nanoparticles (SLNs) loaded with an anti-cancer drug doxorubicin HCl (DOX). DOX encapsulating SLNs were prepared, characterized and further mannosylated. The developed formulations were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle size/ polydispersity index and zeta-potential analysis. The formulations were evaluated for in vitro drug release and hemolytic toxicity. The ex vivo cytotoxicity and cellular uptake studies were performed on A549 cell lines. In vivo studies were conducted to determine pharmacokinetics, tissue distribution pattern and nephrotoxic/ hepatotoxic effect of mannosylated SLNs. In vitro, the formulations exhibited a biphasic pattern characterized by initial rapid release of the drug followed by rather slow and prolonged release. Further, the in vitro studies depicted mannose-conjugated SLNs to be least hemolytic and suitable for sustained drug delivery. Mannosylated SLNs were most cytotoxic and were preferably taken up A549 tumor cells as evaluated against uncoated SLNs and plain DOX. Pharmacokinetic studies revealed improved bioavailability, half life and mean residence time of DOX upon mannose conjugation. The biodistribution pattern exhibited that mannosylated SLNs were able to deliver a higher concentration of DOX in the tumor mass. They were also proficient to circumvent damage to renal as well as hepatic tissues. It may therefore be interpreted that mannosylated SLNs are capable to ferry bioactives selectively and specifically to the tumor sites with the interception of minimal side effects, thereby suggesting their potential application in cancer chemotherapy.
Many novel techniques of extraction such as solvent extraction by soxhlet, ultrasonication and ex... more Many novel techniques of extraction such as solvent extraction by soxhlet, ultrasonication and extraction by boiling of licorice have been well developed. But ultrasonication has been proved as the best and relevant method for extraction of the glycyrrhizin. To optimize the process conditions for the maximum yield of the glycyrrhizin and easier purification, three types of solvents were employed such as water; methanol and ethanol coded as G-1, G-2 and G-3 and extraction was carried out at different time (45, 60 and 120 min). Maximum amount of glycyrrhizin was recovered from licorice roots at 45 °C for 45 min of extraction time, yielded good amount of glycyrrhizin 36.46 ± 1.29 % using water as solvent. In the present work TLC method assessed the purity of the extracted dried sample compared to the licorice standard. The FTIR spectra of the present study indicated that the control/standard of glycyrrhizin was exactly in resemblance with G-1 spectra. The phytochemical screening of extracted glycyrrhizin was conducted which indicated the presence of saponins, flavonoids, steroids and absence of carbohydrate sugars, alkaloids, tannins and proteins in G-1. The glycyrrhizin extracted using different solvents has shown effective antibacterial action on all six microorganism. The antioxidant activity of each sample was determined using DPPH and ABTS scavenging assay. The presence of flavonoids in the plants is likely to be responsible for the free radical scavenging effects observed. Although, it was found that G-1 attained maximum free radical scavenging ability against reactive oxygen species (ROS).
Spirulina platensis, planktonic blue-green algae, has been used as a source of protein (60-70%) a... more Spirulina platensis, planktonic blue-green algae, has been used as a source of protein (60-70%) and vitamin supplement for more than 15 years without any unknown adverse events. Traditionally, Spirulina platensis has been used as an antioxidant agent. However, no pharmacological work has been done to evaluate the anti-anxiety activity. The present study was premeditated for the evaluation of the anti-anxiety activity of Spirulina platensis. Elevated plus maze (EPM) and light-dark models were used to evaluate the anti-anxiety potential of Spirulina platensis in Swiss albino mice. Albino mice were treated orally with diverse doses of the Spirulina platensis (i.e. 300 and 400 mg/kg). Diazepam (2 mg/kg, IP) was used as a standard drug. In conclusion, 400 mg/kg dose of Spirulina platensis showed a significant anti anxiety activity (P<0.05) while control group was near to standard group. It concludes that Spirulina platensis could be useful as an anti-anxiety agent for future prospects.
Spirulina Platensis is a blue-green alga that widely used as a food supplement over worldwide. Tw... more Spirulina Platensis is a blue-green alga that widely used as a food supplement over worldwide. Two models were used to study the effects of Spirulina Platensis on nociception which was induced by acetic acid (Writhing test), formalin (Paw licking test). Spirulina Platensis was administered in the dose range of 200 and 400 mg/kg orally 1 h prior to pain induction. Spirulina Platensis contains β-carotene and biliproteins (phycocyanin and biliphycocyanin). Oral administration of Spirulina Platensis revealed dose-dependent antinociceptive effect in all the models for antinociception and it blocked both the neurogenic and inflammatory pain and the nociceptive activity was comparable with the reference drug. The results indicate that 400 mg/kg dose of Spirulina Platensis showed significant antinociceptive activity. The activity can be related with the significant biliprotein such as phycocyanin and biliphycocyanin that have potent anti-oxidant activity.
Highlight Microencapsulation of lycopene was carried out by coacervation method. Casein and G... more Highlight Microencapsulation of lycopene was carried out by coacervation method. Casein and Gum tragacanth was used as coating material. The microencapsules fabricated at 1:2 of Gt:Cas were also revealed the highest loading capacity and maximum coacervates yield Cumulative lycopene release was estimated 86.34±2.69% from microencapsulated formulations at the end of 24 th hr The stability of lycopene in that formulation in term of % residual content were studied for three months.
The present investigation reports the preparation, optimization, and characterization of surface ... more The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 ± 2.40 nm, PDI 0.307 ± 0.004, entrapment efficiency 72.3 ± 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy.
The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanopar... more The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC 50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.
The current work entails a novel strategy of formulating the microparticles of lycopene solely us... more The current work entails a novel strategy of formulating the microparticles of lycopene solely using rational blends of biopolymers without using equipment-intensive techniques. The study is intended to enhance oral bioavailability of lycopene by controlling its release from micro-formulation and facilitating its absorption though lymphatic pathways. Considering the minimum particle size, maximum entrapment efficiency and loading capacity, the amounts of casein (i.e., protein) and gum tragacanth (i.e., polysaccharide) were selected as the critical factors for formulation of microparticles. Complex formation and electrostatic interaction was confirmed by Fourier transform infra red (FTIR) spectra. Size and surface properties of microparticles were studied using scanning electron microscopy (SEM). The optimized formulation (mean particle size: ∼130 m; % entrapment efficiency: ∼67% and loading capacity: ∼71%) designated noticeable improvement in lycopene release profile (over 80% in 24 h). Increment in the values of C max (2.22-fold) and AUC (1.97-fold) further indicated noteworthy augmentation in the rate and extent of bioavailability by the microparticles formulation compared to plain lycopene. The resulting formulation was found to be quite stable all through two months of study episode. The resultant microparticles formulation was evaluated for antioxidant activity and tested for their effectiveness in self life enhancement of vegetable oil by calculating peroxide value under temperature and storage condition. Encapsulation strongly increased the stability of micronutrients. The current investigations, therefore, report the successful development of biopolymeric microparticles with improved bioavailability potential of lycopene.
Out of many complications two major problems facing in formulation industry are poor solubility a... more Out of many complications two major problems facing in formulation industry are poor solubility and short half-life of drugs which results into poor bioavailability after oral administration. Solid dosage forms are coated for a number of reasons, the most important of which is controlling the release profiles and bioavailability of the active ingredient. Thus the development of a significant dissolution procedure for drug products with limited water solubility has been a challenge to the pharmaceutical industry. Aceclofenac (Biopharmaceutical classification Class II drug) is a novel non-steroidal antiinflammatory drugs (NSAIDs) having anti-inflammatory and analgesic properties, and is widely used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. The investigation revealed that there is no official dissolution medium available in the literature. The objective of present study is to formulate film coated tablet of Aceclofenac and Chlorzoxazone having short half-life by coating with hydroxyl propyl methyl cellulose (E5 LV). Then the formulated tablets were evaluated for its physicochemical properties and in vitro release studies. The incorporation of drugs into polymer matrices is considered a valid tool in order to optimize insufficient features of the drug molecule, like solubility, stability or toxic effects. In the present work, the incorporation of aceclofenac was performed in inert HPMC and there was no chemical interaction between the drug and polymers as concluded from the FTIR studies. In the present study, parameters such as solubility, medium pH, surfactant type, dissolution behavior of formulations, stability, and discriminatory effect of dissolution testing in different dissolution mediums were studied for the selection of a proper dissolution medium. The drug showed an enhanced release rate in the dissolution media containing pH 6.8 phosphate buffer, 900 ml with 0.5 % sodium lauryl sulphate at 75 rpm for 60 min and thus was chosen as the discriminating dissolution method for film coated aceclofenac formulation. It was found that greater than 80 % of the label amount is released over 60 min.
In the last couple of decades antioxidant agents have entered the health market as an easy and at... more In the last couple of decades antioxidant agents have entered the health market as an easy and attractive means of managing diseases. These agents are of enormous interest for an increasingly health-concerned society, and may be particularly relevant for prophylaxis of a number of diseases i.e. arthritis, cancer, metabolic and cardiovascular diseases, osteoporosis, cataracts, brain disorders, etc. Antioxidants are also favorable to vascular healthiness and symbolize useful compounds because they are able to diminish overall cardiovascular risk by acting analogous to first line therapy or as adjuvants in case of failure or in situations where first line therapy cannot be used. Furthermore, well-designed trials are indeed needed to improve the therapeutic efficacy and health benefits of antioxidants. Numerous in vivo proof-of-concepts studies are offered to underline the feasibility of nanostructure system in order to optimizing the delivery of cardiovascular drugs. The present review highlights the recent approaches for management of cardiovascular disease using different vesicular and particulate carriers, including liposomes, nanoparticles, and nanoemulsions, with a primary emphasis on those which are expected to enhance the antioxidants level.
Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, ... more Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, initial protein to polysaccharide mixing ratio (Pr:Ps), total biopolymer concentration, core material load and ionic strength. This study is aimed at understanding how these parameters influence the coacervation kinetics, the coacervate yield, and entrapment efficiency. At a Pr:Ps = 2:1, an optimum pH of complex coacervation was found 4.35, at which the intensity of electrostatic interaction was maximum. At these conditions, the phase separation occurred the fastest and the final coacervate yield and entrapment efficiency were the largest. Moreover, the developed -carotene loaded microcapsules formulation was found to have particle size 159.71 ± 2.16 m, coacervates yield 82.51 ± 0.412%, entrapment efficiency 79.36 ± 0.541%. Varying the Pr:Ps shifted the value of optimum pH. Electrostatic interaction and formation of coacervates was confirmed by Fourier Transform Infra Red (FTIR) spectra. Size and surface properties of coacervates were studied using Scanning Electron Microscopy (SEM). Entrapment of core material within the coacervates was confirmed by Confocal Laser Scanning Microscope (CLSM). The resultant formulation was evaluated for release study and antioxidant activity. Stability of encapsulated -carotene was evaluated under three levels of temperature (5, 25 and 40 • C) for 3 months. Encapsulation strongly increased the stability of micronutrients. Our results advocate potential of microcapsules as a novel carrier for the safeguard and sustained release of micronutrient.
The objective of present study was to enhance permeation of bioactive molecules across blood brai... more The objective of present study was to enhance permeation of bioactive molecules across blood brain barrier (BBB) through polysorbate 80 coated poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with methotrexate-transferrin (Tw-Mtx-Tf-NP) conjugates (Mtx-Tf). The easy trans-BBB migration of developed formulations through endocytosis, and inhibition of P-gp efflux pump present in brain were established by Pluronic F-68 and/or polysorbate 80 (Tween 80/Tw). The over-expression of transferrin (Tf) receptors on cancer cell surface allowed targeted and sustained delivery of Mtx-Tf conjugated to brain cancer cells by receptor mediated endocytosis. The developed formulations showed improved penetration in comparison to non-targeting experimental NP controls. The transportation potential and bio-distribution studies of such nanosized polymeric carriers showing successful migration and trans-BBB passage was carried out by administering FITC labeled drug loaded NPs to albino rats t...
Salient features such as controlled release, target ability, potential of penetration, improved p... more Salient features such as controlled release, target ability, potential of penetration, improved physical stability, low cost compared to phospholipids, and ease of scaling-up makes solid lipid nanoparticles (SLNs) a viable alternative to liposomes for effective drug delivery. Adapalene (ADA) is a second generation retinoid effective in treating various dermatologic disorders such as Acne vulgaris with a few noticeable dose-mediated side effects. The present study was aimed at developing and characterizing ADA loaded SLNs for effective topical delivery. The formulated SLN system was characterized for particle size, poly dispersity index, entrapment efficiency and drug release properties. The resultant formulation (ADA loaded SLNs incorporated into carbopol hydrogel) was evaluated for in vitro drug release, skin permeation and bio-distribution, rheological behaviour, and texture profile analysis. The SLNs based ADA gel has shown its potential in targeting skin epidermal layer, and reducing systemic penetration. The developed system can avoid systemic uptake of ADA in skin layers, and can localize drug in skin epidermis as confirmed by rat skin model. Our results advocate potential of SLNs as a novel carrier for topical delivery of ADA in topical therapeutic approaches. This study open new avenues for drug delivery which better meets the need of anti-acne research.
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Papers by ASHAY JAIN