Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad ... more Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways. It is one of the most lethal forms of cancers accounting to almost 1.8 million new annual incidences, bearing overall mortality to incidence ratio of 0.87. The dismal prognostic scenario at advanced stages of the disease and metastatic/resistant tumor cell populations stresses the requisite of advanced translational interdisciplinary interventions such as bionanotechnology. This review article deliberates insights and apprehensions on the recent prologue of nanobioengineering and bionanotechnology as an approach for the clinical management of lung cancer. The role of nanobioengineered (bio-nano) tools like bio-nanocarriers and nanobiodevices in secondary prophylaxis, diagnosis, therapeutics, and theranostics for lung cancer management has been discussed. Bioengineered, bioinspired, and biomimetic bio-nanotools of considerate translational...
Drug Delivery Devices and Therapeutic Systems, 2021
Abstract Over the last decade, numerous nanomaterial platforms have been established as carrier s... more Abstract Over the last decade, numerous nanomaterial platforms have been established as carrier systems to deliver diverse payloads such as drugs, nucleic acids, peptides, and proteins. Nanoparticles, as drug carriers, possess several advantages, namely high drug loading capacity, target specific delivery, reduced drug toxicity, and controlled drug release. Although active and passive targeting has addressed several important issues, additional modifications to the nanocarrier for attaining spatiotemporal drug release are essential. Spurred by recent advances in material sciences and drug delivery, the fabrication of stimuli-responsive drug delivery systems has gained enormous attention. Controlled by endogenous changes occurring in a diseased condition or by external devices, stimuli-responsive nanocarriers provide enhanced spatiotemporal control, rapid therapeutic effect, and lesser adverse effects at the target site. Recently, external stimuli-responsive drug delivery systems (ultrasound, magnetic, electric, light, and stretch) have gained significant attention as they can be applied remotely allowing spatiotemporal control. This chapter provides insights into recent progress in the field of external stimuli-responsive nanocarriers with a detailed focus on their design, therapeutic benefits, and drug release performance.
Abstract A majority of drug discovery programs lead to the development of drug candidates that ar... more Abstract A majority of drug discovery programs lead to the development of drug candidates that are highly potent and poorly water soluble. Poor drug solubility offers numerous challenges such as reduced bioavailability on oral administration, a lack of equivalence in fed and fasted state, and abandonment of drug molecule in the early stage of drug development. Many strategies, such as micronization, prodrug development, complexation, etc. have been employed for overcoming the drawbacks of poor solubility and subsequently reduced bioavailability of drug. Among these approaches, development of colloidal drug carrier systems have attracted tremendous interest among the scientific community in the last two decades. Lipid nanoparticulate systems (LNS) are emerging as ideal carriers for imparting improved bioavailability of drugs along with controlled release property. Lipid nanoparticulate systems remain a carrier of choice, as they have been claimed to combine all the advantages and avoid disadvantages of other colloidal carriers. Various type of LNSs have been employed for delivery of active molecules viz. solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), drug–lipid conjugates, lipid nanocapsules, liposomes, layersomes and lipid–polymer nanohybrids. These carrier systems are mainly composed of physiologically biocompatible and biodegradable lipid materials, surfactants, and cosurfactants that are generally regarded as safe and accepted by regulatory authorities. This book chapter will mainly focus on two major types of LNS: SLNs and NLCs. The chapter will comprehensively describe the advantages offered by SLNs/NLCs, their structure, type and composition of SLNs/NLCs, methods employed for formulating them, characterization, as well as safety and toxicological aspects of SLNs/NLCs. Furthermore, applications by different routes of administration will also be discussed.
Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 8... more Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC). Paclitaxel (PTX) has been widely used for the treatment of NSCLC. It is classified as a BCS class IV drug and offers a low therapeutic index. The present investigation demonstrates development of orally administered PEGylated, PTX loaded solid lipid nanoparticles (PTX-SLNs). A Box-Behnken design was applied to systematically optimize PTX-SLNs. Drug concentration, emulsifier concentration and homogenization pressure were selected as an independent variables, and particle size, % entrapment efficiency (%EE) and % drug loading (%DL) were selected as dependent variables. The particle size of optimized PTXSLNs was found to be 401 ± 12 nm, with %EE of 86.63 ± 2.58%, and %DL of 7.42 ± 0.11%. The developed PTX-SLNs exhibited anti-lipolytic effect due to its stabilization by MPEG2000-DSPE. Moreover, the in vitro GI stability studies revea...
Background:Conventionally, anti-cancer agents were administered through the intravenous route. Th... more Background:Conventionally, anti-cancer agents were administered through the intravenous route. The major drawbacks associated with the intravenous route of administration are: severe side effects, need of hospitalization, nursing care, and palliative treatment. In order to overcome the drawbacks associated with the intravenous route of administration, oral delivery of anti-cancer agents has gained tremendous interest among the scientific fraternity. Oral delivery of anti-cancer agents principally leads to a reduction in the overall cost of treatment, and aids in improving the quality of life of patients. Bioavailability of drugs and inter-subject variability are the major concerns with oral administration of anti-cancer agents. Factors viz. physicochemical and biological barriers (pre-systemic metabolism and transmembrane efflux of the drug) are accountable for hampering oral bioavailability of anti-cancer agents can be efficiently overcome by employing nanocarrier based drug delive...
Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is ... more Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is the leading cancer killer in both men and women in every Ethnic Group. A major problem associated with chemotherapies against their lung cancer is the lack of selective toxicity, which results in a narrow therapeutic index thereby compromising clinical prognosis. To circumvent these challenges, the present investigation sought to develop a docetaxel-loaded nanostructured lipid carrier system(DTX-NLCS) for the treatment of lung cancer. A 3-factor/3-level Box-Behnken Design was applied to systematically optimize the DTX-NLCS parameters. The amount of drug, emulsifier concentration and homogenization speed were selected as independent variables, while the particle size and % entrapment efficiency(%EE) were selected as dependent variables. The optimized batch parameters were 29.81 mg drug, 19.97% w/w emulsifier, and 13200 (rpm) speed of homogenization with a mean particle size of 154.1±3.13 nm and a mean %EE of 86.12±3.48%. The in vitro lipolysis experiments revealed that the optimized DTX-NLCs was stabilized by 10% w/w PEG 4000 mono-stearate and exhibited an anti-lipolytic effect. Furthermore, the in vitro gastrointestinal stability studies(at pH-1.2, pH-4.5, pH-6.8, and pH-7.4) revealed that the optimized developed system could withstand various GI tract media. The in vitro dissolution studies depicted a pH-independent controlled-release consistent with the Weibull-model. In vitro cytotoxicity studies using NCI-H460 cell lines further revealed that there was a reduction in IC 50 values in the DTX-NLCS treated cells as compared to those treated with the pure drug, indicating an improved efficiency for the developed system.
Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, c... more Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, chemoresistant tumor population, and advanced disease stages. Realization of this fact has now led many of the combination oncotherapies to become an integral part of anticancer regimens. Combination oncotherapy may encompass a combination of anticancer agents belonging to a similar therapeutic category or that of different therapeutic categories (e.g. chemotherapy + gene therapy). Differences in the physicochemical properties, pharmacokinetics and biodistribution pattern of different payloads are the major constraints that are faced by combination chemotherapy. Concordant efforts in the field of nanotechnology and oncology have emerged with several approaches to solve the major issues encountered by combination therapy. Unique colloidal behaviors of various types of nanoparticles and differential targeting strategies have accorded an unprecedented ability to optimize combination oncotherapeutic delivery. Nanocarrier based delivery of the various types of payloads such as chemotherapeutic agents and other anticancer therapeutics such as small interfering ribonucleic acid (siRNA), chemosensitizers, radiosensitizers, and antiangiogenic agents have been addressed in the present review. Various nano-delivery systems like liposomes, polymeric nanoparticles, polymerosomes, dendrimers, micelles, lipid based nanoparticles, prodrug based nanocarriers, polymer-drug conjugates, polymer-lipid hybrid nanoparticles, carbon nanotubes, nanosponges, supramolecular nanocarriers and inorganic nanoparticles (gold nanoparticles, silver nanoparticles, magnetic nanoparticles and mesoporous silica based nanoparticles) that have been extensively explored for the formulation of multidrug delivery is an imperative part of discussion in the review. The present review features the outweighing benefits of combination therapy over monooncotherapy and discusses several existent nanoformulation strategies that facilitate a successful combination oncotherapy. Several obstacles that may impede in transforming nanotechnology-based combination oncotherapy from bench to bedside, and challenges associated therein have also been discussed in the present review.
Artificial cells, nanomedicine, and biotechnology, Jan 16, 2018
The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to ... more The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated using Eudragit S100 coated pellets. The in vivo evaluation of developed system was performed by employing oxazolone colitis rat model. The average particle size of Mn-NLCs (301.7 ± 2.88 nm) was found to be more than that of unconjugated NLCs (284.0 ± 4.53 nm) with marginally reduced % entrapment efficiency (90.88 ± 3.86%). The in vitro cytotoxicity studies using J774A.1 cell l...
The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs)... more The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs) of paclitaxel(FPS) and artemether(FAS). The SLNs were prepared by employing high pressure homogenization technique. The results of MTT assays revealed better cytotoxicity of FPS when given in combination with FAS on human lung cancer cell line H-1299 as compared to pure drugs, unconjugated SLNs and FPS alone. The cellular uptake of FPS and FAS was confirmed by fluorescence imaging and flow cytometric analysis. In-vivo pharmacokinetic study revealed better absorption and long circulation of FPS and FAS, which further leads to increased relative bioavailability of drugs(13.81-folds and 7.07-folds for PTX and ART, respectively) as compared to their solutions counterpart. In-vivo pharmacodynamic study confirmed tumor regression of developed SLNs formulations, which was observed highest when used in combination of FPS and FAS. Serum creatinine, blood urea nitrogen(BUN), SGOT, albumin and total protein levels revealed that formulated FPS and FAS does not exhibit any renal and hepatic toxicity. It can be concluded that by administering ART-SLNs along with PTX-SLNs via oral route, anticancer potential of PTX was improved without any toxicity (both renal, hepatic), thus, indicating the potential of developed formulations in reducing dose related toxicity of PTX.
Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad ... more Lung cancer is a complex thoracic malignancy developing consequential to aberrations in a myriad of molecular and biomolecular signaling pathways. It is one of the most lethal forms of cancers accounting to almost 1.8 million new annual incidences, bearing overall mortality to incidence ratio of 0.87. The dismal prognostic scenario at advanced stages of the disease and metastatic/resistant tumor cell populations stresses the requisite of advanced translational interdisciplinary interventions such as bionanotechnology. This review article deliberates insights and apprehensions on the recent prologue of nanobioengineering and bionanotechnology as an approach for the clinical management of lung cancer. The role of nanobioengineered (bio-nano) tools like bio-nanocarriers and nanobiodevices in secondary prophylaxis, diagnosis, therapeutics, and theranostics for lung cancer management has been discussed. Bioengineered, bioinspired, and biomimetic bio-nanotools of considerate translational...
Drug Delivery Devices and Therapeutic Systems, 2021
Abstract Over the last decade, numerous nanomaterial platforms have been established as carrier s... more Abstract Over the last decade, numerous nanomaterial platforms have been established as carrier systems to deliver diverse payloads such as drugs, nucleic acids, peptides, and proteins. Nanoparticles, as drug carriers, possess several advantages, namely high drug loading capacity, target specific delivery, reduced drug toxicity, and controlled drug release. Although active and passive targeting has addressed several important issues, additional modifications to the nanocarrier for attaining spatiotemporal drug release are essential. Spurred by recent advances in material sciences and drug delivery, the fabrication of stimuli-responsive drug delivery systems has gained enormous attention. Controlled by endogenous changes occurring in a diseased condition or by external devices, stimuli-responsive nanocarriers provide enhanced spatiotemporal control, rapid therapeutic effect, and lesser adverse effects at the target site. Recently, external stimuli-responsive drug delivery systems (ultrasound, magnetic, electric, light, and stretch) have gained significant attention as they can be applied remotely allowing spatiotemporal control. This chapter provides insights into recent progress in the field of external stimuli-responsive nanocarriers with a detailed focus on their design, therapeutic benefits, and drug release performance.
Abstract A majority of drug discovery programs lead to the development of drug candidates that ar... more Abstract A majority of drug discovery programs lead to the development of drug candidates that are highly potent and poorly water soluble. Poor drug solubility offers numerous challenges such as reduced bioavailability on oral administration, a lack of equivalence in fed and fasted state, and abandonment of drug molecule in the early stage of drug development. Many strategies, such as micronization, prodrug development, complexation, etc. have been employed for overcoming the drawbacks of poor solubility and subsequently reduced bioavailability of drug. Among these approaches, development of colloidal drug carrier systems have attracted tremendous interest among the scientific community in the last two decades. Lipid nanoparticulate systems (LNS) are emerging as ideal carriers for imparting improved bioavailability of drugs along with controlled release property. Lipid nanoparticulate systems remain a carrier of choice, as they have been claimed to combine all the advantages and avoid disadvantages of other colloidal carriers. Various type of LNSs have been employed for delivery of active molecules viz. solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), drug–lipid conjugates, lipid nanocapsules, liposomes, layersomes and lipid–polymer nanohybrids. These carrier systems are mainly composed of physiologically biocompatible and biodegradable lipid materials, surfactants, and cosurfactants that are generally regarded as safe and accepted by regulatory authorities. This book chapter will mainly focus on two major types of LNS: SLNs and NLCs. The chapter will comprehensively describe the advantages offered by SLNs/NLCs, their structure, type and composition of SLNs/NLCs, methods employed for formulating them, characterization, as well as safety and toxicological aspects of SLNs/NLCs. Furthermore, applications by different routes of administration will also be discussed.
Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 8... more Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC). Paclitaxel (PTX) has been widely used for the treatment of NSCLC. It is classified as a BCS class IV drug and offers a low therapeutic index. The present investigation demonstrates development of orally administered PEGylated, PTX loaded solid lipid nanoparticles (PTX-SLNs). A Box-Behnken design was applied to systematically optimize PTX-SLNs. Drug concentration, emulsifier concentration and homogenization pressure were selected as an independent variables, and particle size, % entrapment efficiency (%EE) and % drug loading (%DL) were selected as dependent variables. The particle size of optimized PTXSLNs was found to be 401 ± 12 nm, with %EE of 86.63 ± 2.58%, and %DL of 7.42 ± 0.11%. The developed PTX-SLNs exhibited anti-lipolytic effect due to its stabilization by MPEG2000-DSPE. Moreover, the in vitro GI stability studies revea...
Background:Conventionally, anti-cancer agents were administered through the intravenous route. Th... more Background:Conventionally, anti-cancer agents were administered through the intravenous route. The major drawbacks associated with the intravenous route of administration are: severe side effects, need of hospitalization, nursing care, and palliative treatment. In order to overcome the drawbacks associated with the intravenous route of administration, oral delivery of anti-cancer agents has gained tremendous interest among the scientific fraternity. Oral delivery of anti-cancer agents principally leads to a reduction in the overall cost of treatment, and aids in improving the quality of life of patients. Bioavailability of drugs and inter-subject variability are the major concerns with oral administration of anti-cancer agents. Factors viz. physicochemical and biological barriers (pre-systemic metabolism and transmembrane efflux of the drug) are accountable for hampering oral bioavailability of anti-cancer agents can be efficiently overcome by employing nanocarrier based drug delive...
Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is ... more Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is the leading cancer killer in both men and women in every Ethnic Group. A major problem associated with chemotherapies against their lung cancer is the lack of selective toxicity, which results in a narrow therapeutic index thereby compromising clinical prognosis. To circumvent these challenges, the present investigation sought to develop a docetaxel-loaded nanostructured lipid carrier system(DTX-NLCS) for the treatment of lung cancer. A 3-factor/3-level Box-Behnken Design was applied to systematically optimize the DTX-NLCS parameters. The amount of drug, emulsifier concentration and homogenization speed were selected as independent variables, while the particle size and % entrapment efficiency(%EE) were selected as dependent variables. The optimized batch parameters were 29.81 mg drug, 19.97% w/w emulsifier, and 13200 (rpm) speed of homogenization with a mean particle size of 154.1±3.13 nm and a mean %EE of 86.12±3.48%. The in vitro lipolysis experiments revealed that the optimized DTX-NLCs was stabilized by 10% w/w PEG 4000 mono-stearate and exhibited an anti-lipolytic effect. Furthermore, the in vitro gastrointestinal stability studies(at pH-1.2, pH-4.5, pH-6.8, and pH-7.4) revealed that the optimized developed system could withstand various GI tract media. The in vitro dissolution studies depicted a pH-independent controlled-release consistent with the Weibull-model. In vitro cytotoxicity studies using NCI-H460 cell lines further revealed that there was a reduction in IC 50 values in the DTX-NLCS treated cells as compared to those treated with the pure drug, indicating an improved efficiency for the developed system.
Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, c... more Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, chemoresistant tumor population, and advanced disease stages. Realization of this fact has now led many of the combination oncotherapies to become an integral part of anticancer regimens. Combination oncotherapy may encompass a combination of anticancer agents belonging to a similar therapeutic category or that of different therapeutic categories (e.g. chemotherapy + gene therapy). Differences in the physicochemical properties, pharmacokinetics and biodistribution pattern of different payloads are the major constraints that are faced by combination chemotherapy. Concordant efforts in the field of nanotechnology and oncology have emerged with several approaches to solve the major issues encountered by combination therapy. Unique colloidal behaviors of various types of nanoparticles and differential targeting strategies have accorded an unprecedented ability to optimize combination oncotherapeutic delivery. Nanocarrier based delivery of the various types of payloads such as chemotherapeutic agents and other anticancer therapeutics such as small interfering ribonucleic acid (siRNA), chemosensitizers, radiosensitizers, and antiangiogenic agents have been addressed in the present review. Various nano-delivery systems like liposomes, polymeric nanoparticles, polymerosomes, dendrimers, micelles, lipid based nanoparticles, prodrug based nanocarriers, polymer-drug conjugates, polymer-lipid hybrid nanoparticles, carbon nanotubes, nanosponges, supramolecular nanocarriers and inorganic nanoparticles (gold nanoparticles, silver nanoparticles, magnetic nanoparticles and mesoporous silica based nanoparticles) that have been extensively explored for the formulation of multidrug delivery is an imperative part of discussion in the review. The present review features the outweighing benefits of combination therapy over monooncotherapy and discusses several existent nanoformulation strategies that facilitate a successful combination oncotherapy. Several obstacles that may impede in transforming nanotechnology-based combination oncotherapy from bench to bedside, and challenges associated therein have also been discussed in the present review.
Artificial cells, nanomedicine, and biotechnology, Jan 16, 2018
The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to ... more The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated using Eudragit S100 coated pellets. The in vivo evaluation of developed system was performed by employing oxazolone colitis rat model. The average particle size of Mn-NLCs (301.7 ± 2.88 nm) was found to be more than that of unconjugated NLCs (284.0 ± 4.53 nm) with marginally reduced % entrapment efficiency (90.88 ± 3.86%). The in vitro cytotoxicity studies using J774A.1 cell l...
The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs)... more The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs) of paclitaxel(FPS) and artemether(FAS). The SLNs were prepared by employing high pressure homogenization technique. The results of MTT assays revealed better cytotoxicity of FPS when given in combination with FAS on human lung cancer cell line H-1299 as compared to pure drugs, unconjugated SLNs and FPS alone. The cellular uptake of FPS and FAS was confirmed by fluorescence imaging and flow cytometric analysis. In-vivo pharmacokinetic study revealed better absorption and long circulation of FPS and FAS, which further leads to increased relative bioavailability of drugs(13.81-folds and 7.07-folds for PTX and ART, respectively) as compared to their solutions counterpart. In-vivo pharmacodynamic study confirmed tumor regression of developed SLNs formulations, which was observed highest when used in combination of FPS and FAS. Serum creatinine, blood urea nitrogen(BUN), SGOT, albumin and total protein levels revealed that formulated FPS and FAS does not exhibit any renal and hepatic toxicity. It can be concluded that by administering ART-SLNs along with PTX-SLNs via oral route, anticancer potential of PTX was improved without any toxicity (both renal, hepatic), thus, indicating the potential of developed formulations in reducing dose related toxicity of PTX.
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