Prashant Kesharwani - Academia.edu (original) (raw)

Papers by Prashant Kesharwani

Journal of Clinical Medicine

Background: Obesity, and in particular extreme obesity, as a global health problem is an importan... more Background: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. Methods: A systematic literature search in PubMed, Scopus, Embase, and Web of Science as well as grey literature was performed from inception to 1 July 2022. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. Overall, the estimate of effect size was measured by a random e...

Hybrid Nanomaterials for Drug Delivery

Methods in molecular biology, 2022

Methods in molecular biology, 2022

Journal of Drug Delivery Science and Technology

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics, 2019

Abstract Advancement of nanomedicine has come up with different novel delivery strategies to impr... more Abstract Advancement of nanomedicine has come up with different novel delivery strategies to improve the existing chemotherapy. By virtue of nanotechnology, research is ongoing to obtain successful treatment approaches for cancer through active and passive targeted tumor drug delivery and stimulus-responsive tumor microenvironment drug release and penetration using ultrasound, pH, temperature, magnetism, and so on. Use of the building block materials of these nanomedicines is playing a great role to obtain such effects on the final formulations. Biodegradable and biocompatible polyester and polyhydroxyalkanoate polymers are potential areas in the development of nanoparticular delivery systems for cancer chemotherapy. Thus this chapter of the book has focused mainly on these polymer-based nanocarriers in the improvement of chemotherapy to achieve safer and more effective cancer treatment.

Journal of Drug Targeting, 2021

Abstract COVID-19 is a clinical outcome of viral infection emerged due to strain of beta coronavi... more Abstract COVID-19 is a clinical outcome of viral infection emerged due to strain of beta coronavirus which attacks the type-2 pneumocytes in alveoli via angiotensin-converting enzyme 2 (ACE2) receptors. There is no satisfactory drug developed against ‘SARS-CoV2’, highlighting an immediate necessity chemotherapeutic repurposing plan COVID-19. Drug repurposing is a method of selection of approved therapeutics for new use and is considered to be the most effective drug finding strategy since it includes less time and cost to obtain treatment compared to the de novo drug acquisition process. Several drugs such as hydroxychloroquine, remdesivir, teicoplanin, darunavir, ritonavir, nitazoxanide, chloroquine, tocilizumab and favipiravir (FPV) showed their activity against ‘SARS-CoV2’ in vitro. This review has emphasized on repurposing of drugs, and biologics used in clinical set up for targeting COVID-19 and to evaluate their pharmacokinetics, pharmacodynamics and safety with their future aspect. The key benefit of drug repurposing is the wealth of information related to its safety, and easy accessibility. Altogether repurposing approach allows access to regulatory approval as well as reducing sophisticated safety studies.

Nanotechnology-Based Targeted Drug Delivery Systems for Brain Tumors, 2018

Abstract Delivering drugs to the brain is a tedious and challenging task. The promising results f... more Abstract Delivering drugs to the brain is a tedious and challenging task. The promising results from delivery of drugs across the blood–brain barrier using nanosized carriers may be one of the best choices in the future in order to achieve better bioavailability in the brain. Polymeric micelles are self-aggregated nanoscale assemblies of amphiphilic copolymers, preferably in the aqueous phase, and have a size of ≤100 nm. Micellization is facilitated by an attractive force between the hydrophobic and neutral parts of copolymers. Copolymers start self-assembling when the concentration reaches the critical micelle concentration, which is a threshold value for micelle formation. These micelles could be used effectively for the encapsulation of drugs that are usually hydrophobic in nature. The choice of selecting different copolymeric structures is enormous and therefore these carriers are versatile and can be tailored accordingly. The pathways followed for the delivery of drugs to the brain are multiple, including paracellular and transcellular, etc. Specific drug delivery to brain tumors could be beneficial in the future using polymeric micelles.

Journal of Drug Delivery Science and Technology, 2021

Abstract Neurodegenerative diseases are heterogenous group of diseases arises in the diverse segm... more Abstract Neurodegenerative diseases are heterogenous group of diseases arises in the diverse segments of brain such as hippocampus, cerebellum, and brain stem due to protein accumulation, gene mutations, synaptic loss, mitochondrial dysfunction in neuronal cell. Neuronal disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and Prion's disease, caused by combination with multiple factors. Contrast reagents are proficient to access the damaged cells or tissues to crossing blood brain barrier (BBB). All these creates troublesome for the contrasting agents for detection of impairments in the brain. BBB is limits entry of threpaeutic agent in brain there evolved a field in the nanotechnology known as nanotheranostics where both diagnostic and therapeutic effects were achieved. The semiconductor nanocrystals called quantum dots (QDs) are the efficient drug delivery systems accomplishing the objective of theranostic activity. The quantum dots are the zero-dimensional nanostructures with particle size of 2–10 nm, intermediary between bulk semiconductors and discrete molecules owing outstanding optical and electrochemical properties due to their characteristics like luminescence, photostability, electronic properties, high excitation capacity, size tunable emission etc. These features preserve their applicability in the diagnostics, bioimaging, biosensing and therapeutics etc. The QDs show their efficiency in diagnosing and treating the neurodegenerative diseases as they are capable of crossing BBB and biocompatible with the neuronal cells with low cytotoxicity. This article provides the knowledge of quantum dots, their preparation processes and their theranostic activity over the neurodegenerative diseases.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are novel three-dimensional, globular, hyperbranched polymeric nanoparticles ... more Abstract Dendrimers are novel three-dimensional, globular, hyperbranched polymeric nanoparticles synthesized and applied in the medical field since the 1980s. The main distinguishing properties of dendrimers include their nanometric size, monodispersity, void space, and suitability in modification of surface functional groups for therapeutic and biomedical applications. The hydrophobic void space in dendrimers helps to encapsulate hydrophobic therapeutic agents, and it results into enhanced solubility and bioavailability of these poorly water-soluble drugs. Thus, application of dendrimers has been extended to deliver a variety of poorly water-soluble therapeutics, viz. anticancer drugs, antiviral agents, and antimicrobials to obtain enhanced solubility and bioavailability of these drugs. The terminal cationic functional groups of dendrimers are responsible for the latter's toxicity due to their interaction with cell membranes, which leads to disruption of cells. These cationic groups are responsible for toxicity of dendrimers, such as hemolysis, hemolytic toxicity, and cytotoxicity in biological systems, which restricts its use in biological systems. The synthesis of biodegradable dendrimers and surface engineering of cationic dendrimers with neutral, anionic, or biodegradable functional groups are the two options to minimize the associated toxicities of dendrimers. Therefore, the dendrimers synthesized with biodegradable core, branching unit, and surface groups such as polyether, polyesters, and polyether amine result in no or minimal toxic manifestation. Furthermore, the surface engineered dendrimers for modification of their branching units and surface functional groups could be used in conjugation with PEG, carbohydrate, peptides, Tuftsin, folic acids, etc., which contributes to targeted or site-specific delivery of therapeutics. Thus, through this chapter, we emphasize the characteristic of dendrimers responsible for their toxicity, and possible ways to overcome the toxic effects on biological systems.

Journal of Pharmaceutical Sciences, 2021

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene gl... more The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3±0.34°C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.

Dosage Form Design Considerations, 2018

Journal of Pharmaceutical Sciences, 2021

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced u... more This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 hours. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.

Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes, 2017

Abstract Polymeric micelles (PMs) are nanocarriers that are formed by spontaneous arrangement of ... more Abstract Polymeric micelles (PMs) are nanocarriers that are formed by spontaneous arrangement of amphiphilic block copolymers in aqueous solutions. These nanoparticles have a hydrophobic core–hydrophilic shell architecture that facilitates the loading of hydrophobic drugs into the core. This improves the solubility of these drugs. PM-based carriers for drug delivery provide the advantages of ease of preparation and characteristics that can be optimized for a particular target. Furthermore, PMs can be coupled with targeting ligands that enhance their uptake by specific cells, thus reducing off-target side effects. This chapter briefly discusses some of the current PM ligands and targeting strategies, with an emphasis on anticancer drug delivery. In addition, the available core- and shell-forming polymers, and their effects on the stability and characteristics of PMs, are discussed.

Journal of Biomaterials Science, Polymer Edition, 2021

Abstract Dendrimers are macromolecules with high-polymeric branching capable of undergoing major ... more Abstract Dendrimers are macromolecules with high-polymeric branching capable of undergoing major modifications. These characteristics make them an efficient nanocarrier capable of encapsulating and delivering drug, antibodies, or any therapeutic gene. The failure of conventional techniques to deliver drug with higher efficacy and reduced side effects has led to the use of nanomedicines including dendrimers. Dendrimers are novel drug carriers that are modified, complexed, and conjugated with different ligands and receptors to target the delivery of drug at the specific site without impacting any of the normal cells in surrounding. Moreover, the biocompatibility and safety of the dendrimers can be altered accordingly by the process of functionalization by PEGylation, acetylation, or amination. Various dendrimers have been designed to incorporate and deliver anticancer drug either in free form or as codelivery in conjugation with other drugs or therapeutic siRNA/DNA. Doxorubicin (DOX) is one such chemotherapeutic drug that acts by disrupting the process of DNA repair in tumor cells and hence is, since long been used for anticancer therapy. Certain adverse effects such as cardiotoxicity has limited the use of conventional DOX and has shifted the focus on use of safe nanodelivery systems viz dendrimers. DOX either in free or salt form can be loaded or encapsulated accordingly within the core of the dendrimers and linked with different receptors expressed over tumor cells to improve targeting in any cancerous organ site. Positive results obtained after cytotoxicity assay and in vivo/in vitro studies on different cancerous cell lines, and grafted models suggested the potential use of multifunctional DOX–dendrimers characterized with controlled release, better penetration, improved bioavailability, and reduced organ toxicity. This review consolidates studies on different types of DOX-loaded dendrimers that were synthesized, investigated, and are currently being explored for better cancer targeting. Foreseeing the prospects of dendrimers and their compatibility with DOX (free/salt), the article was updated with all current insights.

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics, 2019

Abstract Cancer is a broad term that incorporates various types of tumors that can affect any par... more Abstract Cancer is a broad term that incorporates various types of tumors that can affect any part of the body. Effective treatment of cancer must include targeted chemotherapeutic agents to the particular target cell with minimal side effects and preventing resistance against the chemotherapeutic agent. Nanotechnology has overcome these challenges. Polymeric nanoparticles are a class of nanoparticles in which different polymers are used for encapsulation of the drug. These polymeric nanoparticles are used for targeting particular cancerous cells or tissues by attaching the ligand to it that is having affinity for that particular cell resulting in improvement in stability of the drug. Polymeric nanoparticles are in demand for targeting cancerous tissues with active as well as passive approaches. Exponential use of polymeric nanoparticles for development of chemotherapeutic agents for cancer management has a sophisticated, novel formulation with minimum collateral damage and efficient targeting of therapeutic agents to tumor. In the future, more development of polymers with some therapeutic approaches will impart more use in cancer treatment.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are monodispersed, highly branched macromolecules with nanoscale dimensions. ... more Abstract Dendrimers are monodispersed, highly branched macromolecules with nanoscale dimensions. Dendrimers have a wide variety of biomedical applications such as drug and gene delivery agents, targeting agents, protein mimics, anticancer therapeutics, and contrast agents. Among the various applications, gene or drug delivery by dendrimers is the prime focus of the present-day research. For the successful design of dendrimer-based delivery systems, the dendrimers should be biocompatible and nonimmunogenic. Hence, it is very essential to understand the interactions and effects of dendrimers with biological components like different types of cells, cell organelles, proteins, etc. In this chapter, we have discussed the interaction of dendrimers with cell membranes, components of blood, various targets and factors that influence the interaction with the biological environment, and the consequent effects such as cytotoxicity and hemolysis. We have also discussed different ways to minimize the toxic effects of dendrimers.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are new hyperbranched globular and three-dimensional nanocarrier. Dendrimer n... more Abstract Dendrimers are new hyperbranched globular and three-dimensional nanocarrier. Dendrimer nanocarriers are emergent as most attractive nanocarrier for gene and drug delivery vector. Availability of multiple surface functional groups allow conjugation of targeting moieties which can attract to receptors overexpressed on various cancer cells. It can be concluded that dendrimers show substantial potential as a versatile carrier for bioactives. However, the landing of dendrimer from seat of chemist to formulation desk is still far from complete. Interdisciplinary vision on dendrimer combination with other nanocarriers can be arise as a satisfying strategy. However, the toxicity of the constituents of nanohybrids, vis-a-vis the hybrid itself, will have to be discovered and recognized, if not ruled out.

Journal of Biomaterials Science, Polymer Edition, 2020

Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an ... more Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an antiparasitic, antibacterial and antiviral agent. NTZ is a highly low aqueous soluble drug which possesses solubility of 0.00755 mg/mL and typically low bioavailability of 1%. Low aqueous solubility is usually regarded as prime prerequisites for enhanced absorption and bioavailability. The purpose of this study is to improve in vitro dissolution of the poorly soluble drug NTZ through amorphous solid dispersion technology. Three solid dispersions of NTZ were successfully prepared by hot-melt technique. It was further evaluated for drug content, DSC, XRD, SEM, TEM, FT-IR, in-vitro drug release study, in vitro MTT safety on HEK-293 and A-549 and stability study. The results of XRD showed after the formation of solid dispersions. The number of crystalline peaks has disappeared and confirmed the amorphous form of the drug. An in vitro release study showed that NTZ effectively released from solid dispersion into a simulated gastric releasing medium (pH 1.2). Further, the cytotoxicity study gave an indication of safe for human. Also, stability studies depicted no evident difference in the physical state of solid dispersion after six months. Hence, it can be concluded that the newly developed formulation was found to be safe and stable with enhanced solubility profile.

International Journal of Pharmaceutics, 2021

A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in... more A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in targeting drugs specific to the brain. Neoplasm compromising the internal structure of BBB that results in impaired vasculature is called as blood tumor barrier (BTB). Besides, the BBB serves as a chief hindrance to the passage of a drug into the brain parenchyma. The small and hydrophilic drugs majorly display an absence of desired molecular characteristics required to cross the BBB. Furthermore, all classes of biologics have failed in the clinical trials of brain diseases over the past years since these biologics are large molecules that do not cross the BBB. Also, new strategies have been discovered that use the Trojan horse technology with the re-engineered biologics for BBB transport. Thus, this review delivers information about the different grades of tumors (I-IV) i.e. examples of BBB/BTB heterogenicity along with the different mechanisms for transporting the therapeutics into the brain tumors by crossing BBB. This review also provides insights into the emerging approaches of peptide delivery and the non-invasive and brain-specific molecular Trojan horse targeting technologies. Also, the several challenges in the clinical development of BBB penetrating IgG fusion protein have been discussed.

Journal of Clinical Medicine

Background: Obesity, and in particular extreme obesity, as a global health problem is an importan... more Background: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. Methods: A systematic literature search in PubMed, Scopus, Embase, and Web of Science as well as grey literature was performed from inception to 1 July 2022. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. Overall, the estimate of effect size was measured by a random e...

Hybrid Nanomaterials for Drug Delivery

Methods in molecular biology, 2022

Methods in molecular biology, 2022

Journal of Drug Delivery Science and Technology

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics, 2019

Abstract Advancement of nanomedicine has come up with different novel delivery strategies to impr... more Abstract Advancement of nanomedicine has come up with different novel delivery strategies to improve the existing chemotherapy. By virtue of nanotechnology, research is ongoing to obtain successful treatment approaches for cancer through active and passive targeted tumor drug delivery and stimulus-responsive tumor microenvironment drug release and penetration using ultrasound, pH, temperature, magnetism, and so on. Use of the building block materials of these nanomedicines is playing a great role to obtain such effects on the final formulations. Biodegradable and biocompatible polyester and polyhydroxyalkanoate polymers are potential areas in the development of nanoparticular delivery systems for cancer chemotherapy. Thus this chapter of the book has focused mainly on these polymer-based nanocarriers in the improvement of chemotherapy to achieve safer and more effective cancer treatment.

Journal of Drug Targeting, 2021

Abstract COVID-19 is a clinical outcome of viral infection emerged due to strain of beta coronavi... more Abstract COVID-19 is a clinical outcome of viral infection emerged due to strain of beta coronavirus which attacks the type-2 pneumocytes in alveoli via angiotensin-converting enzyme 2 (ACE2) receptors. There is no satisfactory drug developed against ‘SARS-CoV2’, highlighting an immediate necessity chemotherapeutic repurposing plan COVID-19. Drug repurposing is a method of selection of approved therapeutics for new use and is considered to be the most effective drug finding strategy since it includes less time and cost to obtain treatment compared to the de novo drug acquisition process. Several drugs such as hydroxychloroquine, remdesivir, teicoplanin, darunavir, ritonavir, nitazoxanide, chloroquine, tocilizumab and favipiravir (FPV) showed their activity against ‘SARS-CoV2’ in vitro. This review has emphasized on repurposing of drugs, and biologics used in clinical set up for targeting COVID-19 and to evaluate their pharmacokinetics, pharmacodynamics and safety with their future aspect. The key benefit of drug repurposing is the wealth of information related to its safety, and easy accessibility. Altogether repurposing approach allows access to regulatory approval as well as reducing sophisticated safety studies.

Nanotechnology-Based Targeted Drug Delivery Systems for Brain Tumors, 2018

Abstract Delivering drugs to the brain is a tedious and challenging task. The promising results f... more Abstract Delivering drugs to the brain is a tedious and challenging task. The promising results from delivery of drugs across the blood–brain barrier using nanosized carriers may be one of the best choices in the future in order to achieve better bioavailability in the brain. Polymeric micelles are self-aggregated nanoscale assemblies of amphiphilic copolymers, preferably in the aqueous phase, and have a size of ≤100 nm. Micellization is facilitated by an attractive force between the hydrophobic and neutral parts of copolymers. Copolymers start self-assembling when the concentration reaches the critical micelle concentration, which is a threshold value for micelle formation. These micelles could be used effectively for the encapsulation of drugs that are usually hydrophobic in nature. The choice of selecting different copolymeric structures is enormous and therefore these carriers are versatile and can be tailored accordingly. The pathways followed for the delivery of drugs to the brain are multiple, including paracellular and transcellular, etc. Specific drug delivery to brain tumors could be beneficial in the future using polymeric micelles.

Journal of Drug Delivery Science and Technology, 2021

Abstract Neurodegenerative diseases are heterogenous group of diseases arises in the diverse segm... more Abstract Neurodegenerative diseases are heterogenous group of diseases arises in the diverse segments of brain such as hippocampus, cerebellum, and brain stem due to protein accumulation, gene mutations, synaptic loss, mitochondrial dysfunction in neuronal cell. Neuronal disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and Prion's disease, caused by combination with multiple factors. Contrast reagents are proficient to access the damaged cells or tissues to crossing blood brain barrier (BBB). All these creates troublesome for the contrasting agents for detection of impairments in the brain. BBB is limits entry of threpaeutic agent in brain there evolved a field in the nanotechnology known as nanotheranostics where both diagnostic and therapeutic effects were achieved. The semiconductor nanocrystals called quantum dots (QDs) are the efficient drug delivery systems accomplishing the objective of theranostic activity. The quantum dots are the zero-dimensional nanostructures with particle size of 2–10 nm, intermediary between bulk semiconductors and discrete molecules owing outstanding optical and electrochemical properties due to their characteristics like luminescence, photostability, electronic properties, high excitation capacity, size tunable emission etc. These features preserve their applicability in the diagnostics, bioimaging, biosensing and therapeutics etc. The QDs show their efficiency in diagnosing and treating the neurodegenerative diseases as they are capable of crossing BBB and biocompatible with the neuronal cells with low cytotoxicity. This article provides the knowledge of quantum dots, their preparation processes and their theranostic activity over the neurodegenerative diseases.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are novel three-dimensional, globular, hyperbranched polymeric nanoparticles ... more Abstract Dendrimers are novel three-dimensional, globular, hyperbranched polymeric nanoparticles synthesized and applied in the medical field since the 1980s. The main distinguishing properties of dendrimers include their nanometric size, monodispersity, void space, and suitability in modification of surface functional groups for therapeutic and biomedical applications. The hydrophobic void space in dendrimers helps to encapsulate hydrophobic therapeutic agents, and it results into enhanced solubility and bioavailability of these poorly water-soluble drugs. Thus, application of dendrimers has been extended to deliver a variety of poorly water-soluble therapeutics, viz. anticancer drugs, antiviral agents, and antimicrobials to obtain enhanced solubility and bioavailability of these drugs. The terminal cationic functional groups of dendrimers are responsible for the latter's toxicity due to their interaction with cell membranes, which leads to disruption of cells. These cationic groups are responsible for toxicity of dendrimers, such as hemolysis, hemolytic toxicity, and cytotoxicity in biological systems, which restricts its use in biological systems. The synthesis of biodegradable dendrimers and surface engineering of cationic dendrimers with neutral, anionic, or biodegradable functional groups are the two options to minimize the associated toxicities of dendrimers. Therefore, the dendrimers synthesized with biodegradable core, branching unit, and surface groups such as polyether, polyesters, and polyether amine result in no or minimal toxic manifestation. Furthermore, the surface engineered dendrimers for modification of their branching units and surface functional groups could be used in conjugation with PEG, carbohydrate, peptides, Tuftsin, folic acids, etc., which contributes to targeted or site-specific delivery of therapeutics. Thus, through this chapter, we emphasize the characteristic of dendrimers responsible for their toxicity, and possible ways to overcome the toxic effects on biological systems.

Journal of Pharmaceutical Sciences, 2021

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene gl... more The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3±0.34°C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.

Dosage Form Design Considerations, 2018

Journal of Pharmaceutical Sciences, 2021

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced u... more This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 hours. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.

Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes, 2017

Abstract Polymeric micelles (PMs) are nanocarriers that are formed by spontaneous arrangement of ... more Abstract Polymeric micelles (PMs) are nanocarriers that are formed by spontaneous arrangement of amphiphilic block copolymers in aqueous solutions. These nanoparticles have a hydrophobic core–hydrophilic shell architecture that facilitates the loading of hydrophobic drugs into the core. This improves the solubility of these drugs. PM-based carriers for drug delivery provide the advantages of ease of preparation and characteristics that can be optimized for a particular target. Furthermore, PMs can be coupled with targeting ligands that enhance their uptake by specific cells, thus reducing off-target side effects. This chapter briefly discusses some of the current PM ligands and targeting strategies, with an emphasis on anticancer drug delivery. In addition, the available core- and shell-forming polymers, and their effects on the stability and characteristics of PMs, are discussed.

Journal of Biomaterials Science, Polymer Edition, 2021

Abstract Dendrimers are macromolecules with high-polymeric branching capable of undergoing major ... more Abstract Dendrimers are macromolecules with high-polymeric branching capable of undergoing major modifications. These characteristics make them an efficient nanocarrier capable of encapsulating and delivering drug, antibodies, or any therapeutic gene. The failure of conventional techniques to deliver drug with higher efficacy and reduced side effects has led to the use of nanomedicines including dendrimers. Dendrimers are novel drug carriers that are modified, complexed, and conjugated with different ligands and receptors to target the delivery of drug at the specific site without impacting any of the normal cells in surrounding. Moreover, the biocompatibility and safety of the dendrimers can be altered accordingly by the process of functionalization by PEGylation, acetylation, or amination. Various dendrimers have been designed to incorporate and deliver anticancer drug either in free form or as codelivery in conjugation with other drugs or therapeutic siRNA/DNA. Doxorubicin (DOX) is one such chemotherapeutic drug that acts by disrupting the process of DNA repair in tumor cells and hence is, since long been used for anticancer therapy. Certain adverse effects such as cardiotoxicity has limited the use of conventional DOX and has shifted the focus on use of safe nanodelivery systems viz dendrimers. DOX either in free or salt form can be loaded or encapsulated accordingly within the core of the dendrimers and linked with different receptors expressed over tumor cells to improve targeting in any cancerous organ site. Positive results obtained after cytotoxicity assay and in vivo/in vitro studies on different cancerous cell lines, and grafted models suggested the potential use of multifunctional DOX–dendrimers characterized with controlled release, better penetration, improved bioavailability, and reduced organ toxicity. This review consolidates studies on different types of DOX-loaded dendrimers that were synthesized, investigated, and are currently being explored for better cancer targeting. Foreseeing the prospects of dendrimers and their compatibility with DOX (free/salt), the article was updated with all current insights.

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics, 2019

Abstract Cancer is a broad term that incorporates various types of tumors that can affect any par... more Abstract Cancer is a broad term that incorporates various types of tumors that can affect any part of the body. Effective treatment of cancer must include targeted chemotherapeutic agents to the particular target cell with minimal side effects and preventing resistance against the chemotherapeutic agent. Nanotechnology has overcome these challenges. Polymeric nanoparticles are a class of nanoparticles in which different polymers are used for encapsulation of the drug. These polymeric nanoparticles are used for targeting particular cancerous cells or tissues by attaching the ligand to it that is having affinity for that particular cell resulting in improvement in stability of the drug. Polymeric nanoparticles are in demand for targeting cancerous tissues with active as well as passive approaches. Exponential use of polymeric nanoparticles for development of chemotherapeutic agents for cancer management has a sophisticated, novel formulation with minimum collateral damage and efficient targeting of therapeutic agents to tumor. In the future, more development of polymers with some therapeutic approaches will impart more use in cancer treatment.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are monodispersed, highly branched macromolecules with nanoscale dimensions. ... more Abstract Dendrimers are monodispersed, highly branched macromolecules with nanoscale dimensions. Dendrimers have a wide variety of biomedical applications such as drug and gene delivery agents, targeting agents, protein mimics, anticancer therapeutics, and contrast agents. Among the various applications, gene or drug delivery by dendrimers is the prime focus of the present-day research. For the successful design of dendrimer-based delivery systems, the dendrimers should be biocompatible and nonimmunogenic. Hence, it is very essential to understand the interactions and effects of dendrimers with biological components like different types of cells, cell organelles, proteins, etc. In this chapter, we have discussed the interaction of dendrimers with cell membranes, components of blood, various targets and factors that influence the interaction with the biological environment, and the consequent effects such as cytotoxicity and hemolysis. We have also discussed different ways to minimize the toxic effects of dendrimers.

Dendrimer-Based Nanotherapeutics, 2021

Abstract Dendrimers are new hyperbranched globular and three-dimensional nanocarrier. Dendrimer n... more Abstract Dendrimers are new hyperbranched globular and three-dimensional nanocarrier. Dendrimer nanocarriers are emergent as most attractive nanocarrier for gene and drug delivery vector. Availability of multiple surface functional groups allow conjugation of targeting moieties which can attract to receptors overexpressed on various cancer cells. It can be concluded that dendrimers show substantial potential as a versatile carrier for bioactives. However, the landing of dendrimer from seat of chemist to formulation desk is still far from complete. Interdisciplinary vision on dendrimer combination with other nanocarriers can be arise as a satisfying strategy. However, the toxicity of the constituents of nanohybrids, vis-a-vis the hybrid itself, will have to be discovered and recognized, if not ruled out.

Journal of Biomaterials Science, Polymer Edition, 2020

Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an ... more Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an antiparasitic, antibacterial and antiviral agent. NTZ is a highly low aqueous soluble drug which possesses solubility of 0.00755 mg/mL and typically low bioavailability of 1%. Low aqueous solubility is usually regarded as prime prerequisites for enhanced absorption and bioavailability. The purpose of this study is to improve in vitro dissolution of the poorly soluble drug NTZ through amorphous solid dispersion technology. Three solid dispersions of NTZ were successfully prepared by hot-melt technique. It was further evaluated for drug content, DSC, XRD, SEM, TEM, FT-IR, in-vitro drug release study, in vitro MTT safety on HEK-293 and A-549 and stability study. The results of XRD showed after the formation of solid dispersions. The number of crystalline peaks has disappeared and confirmed the amorphous form of the drug. An in vitro release study showed that NTZ effectively released from solid dispersion into a simulated gastric releasing medium (pH 1.2). Further, the cytotoxicity study gave an indication of safe for human. Also, stability studies depicted no evident difference in the physical state of solid dispersion after six months. Hence, it can be concluded that the newly developed formulation was found to be safe and stable with enhanced solubility profile.

International Journal of Pharmaceutics, 2021

A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in... more A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in targeting drugs specific to the brain. Neoplasm compromising the internal structure of BBB that results in impaired vasculature is called as blood tumor barrier (BTB). Besides, the BBB serves as a chief hindrance to the passage of a drug into the brain parenchyma. The small and hydrophilic drugs majorly display an absence of desired molecular characteristics required to cross the BBB. Furthermore, all classes of biologics have failed in the clinical trials of brain diseases over the past years since these biologics are large molecules that do not cross the BBB. Also, new strategies have been discovered that use the Trojan horse technology with the re-engineered biologics for BBB transport. Thus, this review delivers information about the different grades of tumors (I-IV) i.e. examples of BBB/BTB heterogenicity along with the different mechanisms for transporting the therapeutics into the brain tumors by crossing BBB. This review also provides insights into the emerging approaches of peptide delivery and the non-invasive and brain-specific molecular Trojan horse targeting technologies. Also, the several challenges in the clinical development of BBB penetrating IgG fusion protein have been discussed.