We consider a finite-buffer single server queue with single (multiple) vacation(s) under batch Ma... more We consider a finite-buffer single server queue with single (multiple) vacation(s) under batch Markovian Arrival Process (BMAP). The service discipline is varying number limited service, also called E-limited with limit variation (ELV) where the server serves until either the system is emptied or a randomly chosen limit of l customers have been served. Queue length distributions at various epochs such as, pre-arrival, arbitrary, departure etc. have been obtained. Several other service disciplines like, Bernoulli scheduling, non-exhaustive service and E-limited service can be treated as special cases of the ELV service. Such a queueing system finds applications in the token ring or token bus of local area network (LAN) in which the vacation would correspond to the time the token is away to the other stations.
In this paper, we analyse a multi-server queue with bulk arrivals and finite-buffer space. The in... more In this paper, we analyse a multi-server queue with bulk arrivals and finite-buffer space. The interarrival and service times are arbitrarily and exponentially distributed, respectively. The model is discussed with partial and total batch rejections and the distributions of the numbers of customers in the system at prearrival and arbitrary epochs are obtained. In addition, blocking probabilities and waiting time analyses of the first, an arbitrary and the last customer of a batch are discussed. Finally, some numerical results are presented.
The present investigation was aimed at exploring dendrimer-mediated solubilization and formulatio... more The present investigation was aimed at exploring dendrimer-mediated solubilization and formulation development followed by in vitro, in vivo assessment of piroxicam (PXM) nanocomposite. For this, two dendrimer generations (3.0G and 4.0G) were synthesized and characterized by IR, (1)H NMR spectroscopic and electron microscopy techniques. The optimized formulations containing 0.2% w/v of PXM loaded PAMAM dendrimer at pH 7.4 referred to as 0.2-D(3)P(7.4) (3.0G) and 0.2-D(4)P(7.4) (4.0G) resulted in significant enhancements of PXM solubility approximately by 107- and 222-fold, respectively. The in vitro release behavior of PXM from the formulation in medium-I (PBS 7.4) and medium-II (PBS with 1% albumin) and stability studies were also favorable. Pharmacokinetic study showed higher area under curve (AUC(0-->t); microg/mL/h) of 293.78 +/- 2.04 and 321.54 +/- 2.37 with optimized 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations, respectively, as opposed to 279.11 +/- 1.48 with plain PXM. The elimination half-life of the drug encapsulated in the formulation was significantly higher (0.2-D(3)P(7.4), 36.6 and 0.2-D(4)P(7.4), 41.1; h) than that of pure drug (33.7 h; p < 0.005), and the overall elimination rate constant of formulations was also less as compared to free drug (p < 0.005). Pharmacodynamic assessment by rat-paw model of 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations displayed inhibition levels of 54.21 +/- 1.25% and 59.33 +/- 0.63%, respectively, which are higher than those of plain PXM (41.81 +/- 2.9) formulations, after the sixth hour of administration. The second, fourth and eighth hour organ distribution data showed significantly higher recovery of PXM in rat paw with dendrimer-based formulations in comparison to plain PXM. However, comparison of overall data suggested 4.0G-based formulations to be superior to 3.0G as well as pure PXM.
This paper presents the performance analysis of a discrete-time finite-buffer queue with batch in... more This paper presents the performance analysis of a discrete-time finite-buffer queue with batch input, general interarrival and geometric service times. It is assumed that a batch arriving with size larger than the available buffer is partially accepted and the rest is rejected. The queue is analyzed for early arrival system as well as for late-arrival system with delayed access using both the supplementary variable and imbedded Markov chain techniques. Besides obtaining state probabilities at various epochs and loss probability of a batch as well as of a customer, other performance measures have also been discussed. The waiting time analysis of an arbitrary customer of a batch is also carried out.
Medications that can selectively target tumors at the same time avoid access of the drug to nonta... more Medications that can selectively target tumors at the same time avoid access of the drug to nontarget areas, employ utilization of homing devices termed as ligands, that can bind to specific epitopes expressed on the surface of the necrotic mass of cells. Molecular signatures for transferrin, Epidermal Growth Factor, Sialic Lewis and folic acid are expressed on the surface of these cells. Dendrimers are nanosized, non-immunogenic, and hyper-branched vehicles that can be efficiently tailored for spatial distribution of bioactives, thereby reducing untoward cytotoxicity on normal cells. These nanoparticulate drug delivery vehicles provide a unique platform that has precisely placed functional groups so that multiple copies of ligands can be attached to it and facilitate targeting to the tumor surface or neo-vascularizing vessels proliferating around these cells. The article reviews the scope of ligand based dendritic system as a prospective for delivery of anti-cancer drugs, via active targeting with interception of minimal side effects.
There is a need to understand the nature of drug resistance patterns and predictors of emergence ... more There is a need to understand the nature of drug resistance patterns and predictors of emergence of drug resistance in Mycobacterium tuberculosis. There could be common factors/mechanisms for resistance to the drugs, isoniazid and ethambutol, both acting on cell wall. The present study was conducted to analyze the antimycobacterial susceptibility patterns of M. tuberculosis isolates to determine the minimum inhibitory concentrations (MICs) of ethambutol for M. tuberculosis; and to find out possible association of ethambutol resistance with isoniazid resistance. A total of 380 M. tuberculosis isolates were tested for their susceptibilities to ethambutol at 2, 4, 6 microg/ml, isoniazid at 1 microg/ml and rifampicin at 64 microg/ml using MIC method. 44.21, 24.73 and 14.21 per cent isolates were resistant to ethambutol at concentrations of 2, 4 and 6 microg/ml respectively. At 6 microg/ml of ethambutol concentration, 85.18 per cent ethambutol resistant isolates were resistant to isoniaz...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends ... more The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.
The present study was designed to enhance intestinal absorption of insulin by nanobioconjugate fo... more The present study was designed to enhance intestinal absorption of insulin by nanobioconjugate formulated with PEGylation and Concanavalin A based targeted synergistic approach. The attempts were aimed at maximizing bioavailability and therapeutic efficacy of insulin by incorporating it in Concanavalin A anchored PEGylated nanoconstructs. The Con A anchored PEGylated PLGA diblock copolymer was synthesized by modified surface functionalization method, and was then characterized by FTIR and (1)H NMR spectrum analysis. The nanoparticles from synthesized polymers were prepared and characterized for mean size and distribution by laser diffraction spectroscopy. The physicochemically characterized (by SEM and TEM) formulations were evaluated for optimum particle size, polydispersity index, zeta potential and entrapment efficiency 196.3±4.5nm, 0.15±0.04, -25.6±1.68 and 44.6±3.5% respectively. The insulin encapsulation efficiency and in vitro release were assessed by bicinchoninic protein assay (BCA). The in vitro results corroborated in vivo studies carried out in experimentally created diabetic albino rats. The nano-encapsulated insulin was discovered to meet the requirements by achieving better stability, improved absorption and enhanced oral bioavailability elucidated by in vivo and in vitro bioassays.
Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer... more Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer, AIDS, malaria etc. Cancer is a worldwide threat particularly in developing countries. A breakthrough research in this regard is a prime requirement. In the present study, folic acid was conjugated to fifth generation polypropylene imine (PPI) dendrimers and characterized through IR, NMR ( 13 C and 1 H), ESI mass spectroscopy as well as electron microscopic studies. Doxorubicin (DOX), an effective anticancer drug, was used in the present study to develop and explore the anticancer potential of the dendrimer based formulations. DOX was loaded (approximately 26 and 65%) to the PPI dendrimers as well as folate conjugated PPI (PPI-FA) dendrimers, respectively. These ligand conjugated dendrimers displayed very less (approximately 3 and 4%, respectively, for PPI-FA and PPI-FA-DOX) hemolysis. The developed formulation PPI-FA-DOX was stable enough. In vitro drug release of the formulation was found to be faster in the acidic media than at the higher pH. The prepared formulation displayed a higher cell uptake in MCF-7 cancer cell lines as evidenced by fluorescence studies. The results suggested that, in future, folic acid conjugated PPI dendrimers may emerge as a better choice for anticancer drug targeting.
In this paper, we consider the discrete-time bulk-arrival GIX/G/1 queue and propose a simple proc... more In this paper, we consider the discrete-time bulk-arrival GIX/G/1 queue and propose a simple procedure for computing waiting-time probabilities of the first and the random customers. As can be seen from our analysis that even analytic procedure is simpler than the one discussed by Murata and Miyahara [Perf. Eval. 13 (1991) 87]. Further, the procedure discussed here works for both
Nanomedicine : nanotechnology, biology, and medicine, 2006
Dendrimers have emerged as one of the most interesting themes for researchers as a result of thei... more Dendrimers have emerged as one of the most interesting themes for researchers as a result of their unique architecture and macromolecular characteristics. Several groups are involved in exploring their potential as versatile carriers in drug delivery. The use of dendrimers in drug delivery has been reviewed extensively. The increasing relevance of the potential of dendrimers in drug delivery emphasizes the need to explore the routes by which they can be administered. The present review focuses on dendrimer-mediated drug delivery based on various routes of administration, a topic that has received little attention in the available literature. With this focus in mind, we present a comprehensive exploration of the recent advances in the investigational aspects of these nanoscopic polymeric devices. Also included are some in vitro studies that present data suggestive of their possible application in different routes of administration.
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2007
Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromole... more Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromolecular nano-scopic architecture with number of reactive end groups. Dendrimers have been reported to act as solubilizing agents to host both hydrophilic and hydrophobic drugs. The present study was performed to investigate the effect of pH on poly(propylene) imine dendrimers (5.0G) mediated solubility enhancement of hydrophobes differing in functional groups (pKa). Weakly basic, (famotidine, -NH2 functional group; pKa 7.1), weakly acidic (indomethacin, -COOH functional group; pKa 4.5) and amphoteric (amphotericin B, -COOH and -NH2 functional groups; pKa 5.7 and 10.0) hydrophobes were selected for the study. The experiment was carried out at pH 4.0, 7.4 and 10.0. The solubility of all the drugs was enhanced at pH 7.4 and 10.0 but not at pH 4.0. The drug-dendrimer complexes followed 1:1 stoichiometry (AL type of curve) and were characterized for stability of complex, complexation efficiency...
Proceedings of the 2nd International ICST Conference on Performance Evaluation Methodologies and Tools, 2007
INRIA, Rennes (IRISA), Campus De Beaulieu 35042 Rennes Cedex France [email protected], banikad@gm... more INRIA, Rennes (IRISA), Campus De Beaulieu 35042 Rennes Cedex France [email protected], [email protected] ... Umesh Chandra Gupta Department of Mathematics, Indian Institute of Technology Kharagpur-721302, India [email protected]
The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nano... more The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticulate delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through transmission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistribution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264 ± 11.2 nm with low PDI suggesting the narrow particle size distribution. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis.
Dendrimers are well-defined, versatile polymeric architecture with properties resembling biomolec... more Dendrimers are well-defined, versatile polymeric architecture with properties resembling biomolecules. Dendritic polymers emerged as outstanding carrier in modern medicine system because of its derivatisable branched architecture and flexibility in modifying it in numerous ways. Dendritic scaffold has been found to be suitable carrier for a variety of drugs including anticancer, anti-viral, anti-bacterial, antitubercular etc., with capacity to improve solubility and bioavailability of poorly soluble drugs. In spite of extensive applicability in pharmaceutical field, the use of dendrimers in biological system is constrained because of inherent toxicity associated with them. This toxicity is attributed to the interaction of surface cationic charge of dendrimers with negatively charged biological membranes in vivo. Interaction of dendrimers with biological membranes results in membrane disruption via nanohole formation, membrane thinning and erosion. Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity and hematological toxicity. To minimize this toxicity two strategies have been utilized; first, designing and synthesis of biocompatible dendrimers; and second, masking of peripheral charge of dendrimers by surface engineering. Biocompatible dendrimers can be synthesized by employing biodegradable core and branching units or utilizing intermediates of various metabolic pathways. Dendrimer biocompatibility has been evaluated in vitro and in vivo for efficient presentation of biological performance. Surface engineering masks the cationic charge of dendrimer surface either by neutralization of charge, for example PEGylation, acetylation, carbohydrate and peptide conjugation; or by introducing negative charge such as half generation dendrimers. Neutral and negatively charged dendrimers do not interact with biological environment and hence are compatible for clinical applications as elucidated by various studies examined in this review. Chemical modification of the surface is an important strategy to overcome the toxicity problems associated with the dendrimers. The present review emphasizes on the approaches available to overcome the cationic toxicity inherently associated with the dendrimers.
Blood samples of 40 pregnant women were analysed for glycosylated haemoglobin (HbA1c) and blood s... more Blood samples of 40 pregnant women were analysed for glycosylated haemoglobin (HbA1c) and blood sugar. The patients were followed up till delivery and their obstetric outcome was analysed in conjunction with the glycaemic profile and the level of glycosylated haemoglobin. Group I comprising the normal pregnant women showed a mean HbA1c of 6.23% at 20–40 weeks of gestation. In contrast
In this paper, we consider a single-server finite-capacity queue with general bulk service rule w... more In this paper, we consider a single-server finite-capacity queue with general bulk service rule where customers arrive according to a Poisson process and service times of the batches are arbitrarily distributed. The queue is analyzed using both the supplementary variable and imbedded Markov chain techniques. The relations between state probabilities at departure and arbitrary epochs have been presented in explicit
We consider a finite-buffer single server queue with single (multiple) vacation(s) under batch Ma... more We consider a finite-buffer single server queue with single (multiple) vacation(s) under batch Markovian Arrival Process (BMAP). The service discipline is varying number limited service, also called E-limited with limit variation (ELV) where the server serves until either the system is emptied or a randomly chosen limit of l customers have been served. Queue length distributions at various epochs such as, pre-arrival, arbitrary, departure etc. have been obtained. Several other service disciplines like, Bernoulli scheduling, non-exhaustive service and E-limited service can be treated as special cases of the ELV service. Such a queueing system finds applications in the token ring or token bus of local area network (LAN) in which the vacation would correspond to the time the token is away to the other stations.
In this paper, we analyse a multi-server queue with bulk arrivals and finite-buffer space. The in... more In this paper, we analyse a multi-server queue with bulk arrivals and finite-buffer space. The interarrival and service times are arbitrarily and exponentially distributed, respectively. The model is discussed with partial and total batch rejections and the distributions of the numbers of customers in the system at prearrival and arbitrary epochs are obtained. In addition, blocking probabilities and waiting time analyses of the first, an arbitrary and the last customer of a batch are discussed. Finally, some numerical results are presented.
The present investigation was aimed at exploring dendrimer-mediated solubilization and formulatio... more The present investigation was aimed at exploring dendrimer-mediated solubilization and formulation development followed by in vitro, in vivo assessment of piroxicam (PXM) nanocomposite. For this, two dendrimer generations (3.0G and 4.0G) were synthesized and characterized by IR, (1)H NMR spectroscopic and electron microscopy techniques. The optimized formulations containing 0.2% w/v of PXM loaded PAMAM dendrimer at pH 7.4 referred to as 0.2-D(3)P(7.4) (3.0G) and 0.2-D(4)P(7.4) (4.0G) resulted in significant enhancements of PXM solubility approximately by 107- and 222-fold, respectively. The in vitro release behavior of PXM from the formulation in medium-I (PBS 7.4) and medium-II (PBS with 1% albumin) and stability studies were also favorable. Pharmacokinetic study showed higher area under curve (AUC(0-->t); microg/mL/h) of 293.78 +/- 2.04 and 321.54 +/- 2.37 with optimized 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations, respectively, as opposed to 279.11 +/- 1.48 with plain PXM. The elimination half-life of the drug encapsulated in the formulation was significantly higher (0.2-D(3)P(7.4), 36.6 and 0.2-D(4)P(7.4), 41.1; h) than that of pure drug (33.7 h; p < 0.005), and the overall elimination rate constant of formulations was also less as compared to free drug (p < 0.005). Pharmacodynamic assessment by rat-paw model of 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations displayed inhibition levels of 54.21 +/- 1.25% and 59.33 +/- 0.63%, respectively, which are higher than those of plain PXM (41.81 +/- 2.9) formulations, after the sixth hour of administration. The second, fourth and eighth hour organ distribution data showed significantly higher recovery of PXM in rat paw with dendrimer-based formulations in comparison to plain PXM. However, comparison of overall data suggested 4.0G-based formulations to be superior to 3.0G as well as pure PXM.
This paper presents the performance analysis of a discrete-time finite-buffer queue with batch in... more This paper presents the performance analysis of a discrete-time finite-buffer queue with batch input, general interarrival and geometric service times. It is assumed that a batch arriving with size larger than the available buffer is partially accepted and the rest is rejected. The queue is analyzed for early arrival system as well as for late-arrival system with delayed access using both the supplementary variable and imbedded Markov chain techniques. Besides obtaining state probabilities at various epochs and loss probability of a batch as well as of a customer, other performance measures have also been discussed. The waiting time analysis of an arbitrary customer of a batch is also carried out.
Medications that can selectively target tumors at the same time avoid access of the drug to nonta... more Medications that can selectively target tumors at the same time avoid access of the drug to nontarget areas, employ utilization of homing devices termed as ligands, that can bind to specific epitopes expressed on the surface of the necrotic mass of cells. Molecular signatures for transferrin, Epidermal Growth Factor, Sialic Lewis and folic acid are expressed on the surface of these cells. Dendrimers are nanosized, non-immunogenic, and hyper-branched vehicles that can be efficiently tailored for spatial distribution of bioactives, thereby reducing untoward cytotoxicity on normal cells. These nanoparticulate drug delivery vehicles provide a unique platform that has precisely placed functional groups so that multiple copies of ligands can be attached to it and facilitate targeting to the tumor surface or neo-vascularizing vessels proliferating around these cells. The article reviews the scope of ligand based dendritic system as a prospective for delivery of anti-cancer drugs, via active targeting with interception of minimal side effects.
There is a need to understand the nature of drug resistance patterns and predictors of emergence ... more There is a need to understand the nature of drug resistance patterns and predictors of emergence of drug resistance in Mycobacterium tuberculosis. There could be common factors/mechanisms for resistance to the drugs, isoniazid and ethambutol, both acting on cell wall. The present study was conducted to analyze the antimycobacterial susceptibility patterns of M. tuberculosis isolates to determine the minimum inhibitory concentrations (MICs) of ethambutol for M. tuberculosis; and to find out possible association of ethambutol resistance with isoniazid resistance. A total of 380 M. tuberculosis isolates were tested for their susceptibilities to ethambutol at 2, 4, 6 microg/ml, isoniazid at 1 microg/ml and rifampicin at 64 microg/ml using MIC method. 44.21, 24.73 and 14.21 per cent isolates were resistant to ethambutol at concentrations of 2, 4 and 6 microg/ml respectively. At 6 microg/ml of ethambutol concentration, 85.18 per cent ethambutol resistant isolates were resistant to isoniaz...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends ... more The outcome of the interaction between Mycobacterium tuberculosis (Mtb) and a macrophage depends on the interplay between host defense and bacterial immune subversion mechanisms. MicroRNAs critically regulate several host defense mechanisms, but their role in the Mtb-macrophage interplay remains unclear. MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6. We establish that let-7f targets A20, a feedback inhibitor of the NF-κB pathway. Expression of let-7f decreases and A20 increases with progression of Mtb infection in mice. Mtb survival is attenuated in A20-deficient macrophages, and the production of TNF, IL-1β, and nitrite, which are mediators of immunity to Mtb, is correspondingly increased. Further, let-7f overexpression diminishes Mtb survival and augments the production of cytokines including TNF and IL-1β. These results uncover a role for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.
The present study was designed to enhance intestinal absorption of insulin by nanobioconjugate fo... more The present study was designed to enhance intestinal absorption of insulin by nanobioconjugate formulated with PEGylation and Concanavalin A based targeted synergistic approach. The attempts were aimed at maximizing bioavailability and therapeutic efficacy of insulin by incorporating it in Concanavalin A anchored PEGylated nanoconstructs. The Con A anchored PEGylated PLGA diblock copolymer was synthesized by modified surface functionalization method, and was then characterized by FTIR and (1)H NMR spectrum analysis. The nanoparticles from synthesized polymers were prepared and characterized for mean size and distribution by laser diffraction spectroscopy. The physicochemically characterized (by SEM and TEM) formulations were evaluated for optimum particle size, polydispersity index, zeta potential and entrapment efficiency 196.3±4.5nm, 0.15±0.04, -25.6±1.68 and 44.6±3.5% respectively. The insulin encapsulation efficiency and in vitro release were assessed by bicinchoninic protein assay (BCA). The in vitro results corroborated in vivo studies carried out in experimentally created diabetic albino rats. The nano-encapsulated insulin was discovered to meet the requirements by achieving better stability, improved absorption and enhanced oral bioavailability elucidated by in vivo and in vitro bioassays.
Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer... more Dendrimers are considered versatile carriers especially for the treatment of diseases like cancer, AIDS, malaria etc. Cancer is a worldwide threat particularly in developing countries. A breakthrough research in this regard is a prime requirement. In the present study, folic acid was conjugated to fifth generation polypropylene imine (PPI) dendrimers and characterized through IR, NMR ( 13 C and 1 H), ESI mass spectroscopy as well as electron microscopic studies. Doxorubicin (DOX), an effective anticancer drug, was used in the present study to develop and explore the anticancer potential of the dendrimer based formulations. DOX was loaded (approximately 26 and 65%) to the PPI dendrimers as well as folate conjugated PPI (PPI-FA) dendrimers, respectively. These ligand conjugated dendrimers displayed very less (approximately 3 and 4%, respectively, for PPI-FA and PPI-FA-DOX) hemolysis. The developed formulation PPI-FA-DOX was stable enough. In vitro drug release of the formulation was found to be faster in the acidic media than at the higher pH. The prepared formulation displayed a higher cell uptake in MCF-7 cancer cell lines as evidenced by fluorescence studies. The results suggested that, in future, folic acid conjugated PPI dendrimers may emerge as a better choice for anticancer drug targeting.
In this paper, we consider the discrete-time bulk-arrival GIX/G/1 queue and propose a simple proc... more In this paper, we consider the discrete-time bulk-arrival GIX/G/1 queue and propose a simple procedure for computing waiting-time probabilities of the first and the random customers. As can be seen from our analysis that even analytic procedure is simpler than the one discussed by Murata and Miyahara [Perf. Eval. 13 (1991) 87]. Further, the procedure discussed here works for both
Nanomedicine : nanotechnology, biology, and medicine, 2006
Dendrimers have emerged as one of the most interesting themes for researchers as a result of thei... more Dendrimers have emerged as one of the most interesting themes for researchers as a result of their unique architecture and macromolecular characteristics. Several groups are involved in exploring their potential as versatile carriers in drug delivery. The use of dendrimers in drug delivery has been reviewed extensively. The increasing relevance of the potential of dendrimers in drug delivery emphasizes the need to explore the routes by which they can be administered. The present review focuses on dendrimer-mediated drug delivery based on various routes of administration, a topic that has received little attention in the available literature. With this focus in mind, we present a comprehensive exploration of the recent advances in the investigational aspects of these nanoscopic polymeric devices. Also included are some in vitro studies that present data suggestive of their possible application in different routes of administration.
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2007
Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromole... more Dendrimers today are known for their three dimensional, monodispersed, highly branched, macromolecular nano-scopic architecture with number of reactive end groups. Dendrimers have been reported to act as solubilizing agents to host both hydrophilic and hydrophobic drugs. The present study was performed to investigate the effect of pH on poly(propylene) imine dendrimers (5.0G) mediated solubility enhancement of hydrophobes differing in functional groups (pKa). Weakly basic, (famotidine, -NH2 functional group; pKa 7.1), weakly acidic (indomethacin, -COOH functional group; pKa 4.5) and amphoteric (amphotericin B, -COOH and -NH2 functional groups; pKa 5.7 and 10.0) hydrophobes were selected for the study. The experiment was carried out at pH 4.0, 7.4 and 10.0. The solubility of all the drugs was enhanced at pH 7.4 and 10.0 but not at pH 4.0. The drug-dendrimer complexes followed 1:1 stoichiometry (AL type of curve) and were characterized for stability of complex, complexation efficiency...
Proceedings of the 2nd International ICST Conference on Performance Evaluation Methodologies and Tools, 2007
INRIA, Rennes (IRISA), Campus De Beaulieu 35042 Rennes Cedex France [email protected], banikad@gm... more INRIA, Rennes (IRISA), Campus De Beaulieu 35042 Rennes Cedex France [email protected], [email protected] ... Umesh Chandra Gupta Department of Mathematics, Indian Institute of Technology Kharagpur-721302, India [email protected]
The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nano... more The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticulate delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through transmission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistribution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264 ± 11.2 nm with low PDI suggesting the narrow particle size distribution. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis.
Dendrimers are well-defined, versatile polymeric architecture with properties resembling biomolec... more Dendrimers are well-defined, versatile polymeric architecture with properties resembling biomolecules. Dendritic polymers emerged as outstanding carrier in modern medicine system because of its derivatisable branched architecture and flexibility in modifying it in numerous ways. Dendritic scaffold has been found to be suitable carrier for a variety of drugs including anticancer, anti-viral, anti-bacterial, antitubercular etc., with capacity to improve solubility and bioavailability of poorly soluble drugs. In spite of extensive applicability in pharmaceutical field, the use of dendrimers in biological system is constrained because of inherent toxicity associated with them. This toxicity is attributed to the interaction of surface cationic charge of dendrimers with negatively charged biological membranes in vivo. Interaction of dendrimers with biological membranes results in membrane disruption via nanohole formation, membrane thinning and erosion. Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity and hematological toxicity. To minimize this toxicity two strategies have been utilized; first, designing and synthesis of biocompatible dendrimers; and second, masking of peripheral charge of dendrimers by surface engineering. Biocompatible dendrimers can be synthesized by employing biodegradable core and branching units or utilizing intermediates of various metabolic pathways. Dendrimer biocompatibility has been evaluated in vitro and in vivo for efficient presentation of biological performance. Surface engineering masks the cationic charge of dendrimer surface either by neutralization of charge, for example PEGylation, acetylation, carbohydrate and peptide conjugation; or by introducing negative charge such as half generation dendrimers. Neutral and negatively charged dendrimers do not interact with biological environment and hence are compatible for clinical applications as elucidated by various studies examined in this review. Chemical modification of the surface is an important strategy to overcome the toxicity problems associated with the dendrimers. The present review emphasizes on the approaches available to overcome the cationic toxicity inherently associated with the dendrimers.
Blood samples of 40 pregnant women were analysed for glycosylated haemoglobin (HbA1c) and blood s... more Blood samples of 40 pregnant women were analysed for glycosylated haemoglobin (HbA1c) and blood sugar. The patients were followed up till delivery and their obstetric outcome was analysed in conjunction with the glycaemic profile and the level of glycosylated haemoglobin. Group I comprising the normal pregnant women showed a mean HbA1c of 6.23% at 20–40 weeks of gestation. In contrast
In this paper, we consider a single-server finite-capacity queue with general bulk service rule w... more In this paper, we consider a single-server finite-capacity queue with general bulk service rule where customers arrive according to a Poisson process and service times of the batches are arbitrarily distributed. The queue is analyzed using both the supplementary variable and imbedded Markov chain techniques. The relations between state probabilities at departure and arbitrary epochs have been presented in explicit
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Papers by Umesh Gupta