Tathagata Dutta - Academia.edu (original) (raw)

Papers by Tathagata Dutta

Therapeutic agents in cancer treatment are aimed at rapidly dividing cells, limiting their multip... more Therapeutic agents in cancer treatment are aimed at rapidly dividing cells, limiting their multiplication, and promoting apoptosis. Lack of selectivity of these conventional methods resulted in needless damage to normal cells leading to severe adverse effects. Nanotechnology in medicine gratify the constraint in conventional treatment by delivering conventional drugs to the targeted tissue or organ and plays an important role in targeting the delivery, thereby avoiding systemic toxicity and increasing the bioavailability and therapeutic index of the drug. The advantage of using nanoparticles as drug carriers is in their binding competence and reversing multidrug resistance. Using active and passive targeting strategies, nanoparticles enhance intracellular drug concentrations. The present review focuses the on the basic pathophysiology of cancer and the various types of nanoparticulate drug delivery systems that have been explored so far, taking advantage of the tumour vasculature an...

A novel stability indicating RP-HPLC method having a very short run time was developed and valida... more A novel stability indicating RP-HPLC method having a very short run time was developed and validated for determination of assay of Voriconazole in bulk solution, lyophilized injectable dosage form and in physiological compatible solutions. The method is novel, rapid, precise, accurate and capable of separating known impurities and degradants from Voriconazole peak proving the stability-indicating nature of the method. The analytical method consists of isocratic elution at a flow rate of 0.8 mL/min on a Devolosil C18 column (100 x 4.6 mm, 3μm) at temperature of 45°C and UV detection wavelength of 254 nm. 10μL of the voriconazole sample was injected and peak was eluted at about 2.5 min. with total run time of 10 minutes. The % recovery was well within the range between 98% and 102%. The RSD for precision and accuracy of the method was found to be less than 2%. The method was validated as per the International Conference on Harmonization (ICH) guidelines and can be successfully applied...

Anthropologischer Anzeiger, 2006

Basic causes of poor state of nutrition and infections in developing countries are poverty, low l... more Basic causes of poor state of nutrition and infections in developing countries are poverty, low level of hygienic conditions and little access to preventive and health care. Central India is known for its high rate of population growth and mortality, which persisted over time along with a low level of social, economic and infrastructure development. In the present study the body mass index (BMI) of 31 populations residing in 38 districts of Central India (comprising the States of Madhya Pradesh and Chhattisgarh) is assessed. Anthropometric data collected by the Anthropological Survey of India were utilized in this context. The mean body mass index values of the populations of total backward and non-backward districts are found to be lower than that of well-to-do individuals of India (Bharati 1989, Khongsdier 1997, Reddy 1998), but it is not as low as that found among the South Indian populations (Ferro-Luzzi et al. 1992). In the present investigation, it is also found that the majority of the backward districts fall in the category of different grade of chronic energy deficiency (CED), while in the non-backward districts a considerably less number of districts follows this trend. A better level of the nutritional status among the populations of the non-backward districts corroborates the findings of the Ministry of Health and Family Welfare (NFHS 1992). It reveals that the apparently healthy individuals with CED grade I in the present study may be thin but physically active and healthy. The present study, however, narrates further intensive investigations in these populations, because the BMI as a measure of the CED should incorporate the aspects like morbidity and health status of a population.

Pharmazie

The objective of the study was to design and evaluate a solid lipid nanoparticle (SLN) drug deliv... more The objective of the study was to design and evaluate a solid lipid nanoparticle (SLN) drug delivery system for delivery of paclitaxel. Components of the SLN were lipid (stearylamine) and surfactants (Pluronic F68 and Soya lecithin). The paclitaxel loaded nanoparticles were prepared by a modified solvent injection method. Experiments were carried out with excipients, where surfactants, lipid and drug molar ratios were varied to optimize the formulation characteristics. The in vitro drug release profile from the nanoparticles followed a diffusion controlled mechanism. The modified solvent injection method ensured high entrapment efficiency (approximately 75%), produced smaller, stable nanoparticles with a narrow size distribution and proved to be a reproducible and fast production method. The present study describes the feasibility and suitability of stearylamine based SLN produced using a mixture of surfactants to develop a clinically useful system with targeting potential for poorl...

Pharmazie

This study investigates the design and characterization of solid lipid nanoparticles (SLNs) conta... more This study investigates the design and characterization of solid lipid nanoparticles (SLNs) containing paclitaxel fabricated by a modified solvent injection technique using stearic acid as lipid and stabilized by a mixture of surfactants, for future evaluation of this colloidal carrier system for the oral delivery of paclitaxel, devoid of the side effects of Cremophor EL. SLN formulations of paclitaxel stabilized by mixture of surfactants i.e. lecithin/poloxamer 188 were developed with smaller size and narrow size distribution. The paclitaxel-loaded SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The average particle size obtained through this method was found to be approximately 113 nm. The zeta potential was between -32 and -39 mV with poloxamer 188. Encapsulation efficiencies of about 72.18 +/- 3.7 and 89.0 +/- 2.4% were achieved using 0.05 and 0.25 mmol of paclitaxel, respectively. Paclitaxel showed a sustained in vitro r...

Nanotoxicology, 2008

Dendrimers are three dimensional polymers, nanoscopic in size, most widely explored in the field ... more Dendrimers are three dimensional polymers, nanoscopic in size, most widely explored in the field of drug delivery in recent times. In order to establish these polymers as controlled and targeted drug delivery systems, they should be non-toxic, biocompatible and biodegradable. The ...

Nanomedicine: Nanotechnology, Biology and Medicine, 2007

The purpose of this work was to study the biodistribution pattern of the fifth generation of poly... more The purpose of this work was to study the biodistribution pattern of the fifth generation of poly(propylene imine) dendrimer (PPI-5.0G)-based carbohydrate (mannose and lactose)-coated glycodendrimers in mice so as to explore the potential of these systems as drug carriers. Plain dendrimers were synthesized and coated with carbohydrates following the reported procedures. The formulations were labeled with radioactive technetium (sodium pertechnetate; 99mTcO4-) and characterized for labeling efficiency as well as in vitro and in vivo stability of the labeled complexes. The blood clearance study was performed in female New Zealand rabbits. The periodic in vivo biodistribution profile of the formulations was investigated in female Balb/c mice. The dendrimeric formulations were labeled with 95% labeling efficiency. The labeled complexes were found to be stable in vitro (97% to 98% stability) and in vivo (89% to 94% stability). All the formulations were cleared rapidly from circulation; clearance of mannose-coated poly (propylene imine) dendrimer (M-PPI) and lactose-coated poly(propylene imine) dendrimer (L-PPI) was faster than PPI-5.0G. All the formulations accumulated in liver to a significant extent, but only those with terminal carbohydrate moieties were retained for a longer period. Significant accumulation of PPI-5.0G and M-PPI was observed in kidneys as against very less activity in the case of L-PPI. Rapid clearance of the dendrimers was in accordance with the earlier reports. Higher and prolonged retention of M-PPI and L-PPI in liver was attributed to lectin-carbohydrate interactions. Lesser accumulation of L-PPI in kidneys was suggestive of its lesser excretion. This observation can be explained on the basis of the molecular weight of L-PPI, which was greater than the threshold of glomerular excretion. In general, it was observed that the carbohydrate-coated dendrimers were distributed in liver to a significant extent. This information could serve as a useful platform in designing carbohydrate-coated dendrimers for selective delivery of bioactive agents to liver.

Pharmaceutical Medicine, 2022

The therapeutic potential for messenger RNA (mRNA) in infectious diseases and cancer was first re... more The therapeutic potential for messenger RNA (mRNA) in infectious diseases and cancer was first realized almost three decades ago, but only in 2018 did the first lipid nanoparticle-based small interfering RNA (siRNA) therapy reach the market with the United States Food and Drug Administration (FDA) approval of patisiran (Onpattro™) for hereditary ATTR amyloidosis. This was largely made possible by major advances in the formulation technology for stabilized lipid-based nanoparticles (LNPs). Design of the cationic ionizable lipids, which are a key component of the LNP formulations, with an acid dissociation constant (pKa) close to the early endosomal pH, would not only ensure effective encapsulation of mRNA into the stabilized lipoplexes within the LNPs, but also its subsequent endosomal release into the cytoplasm after endocytosis. Unlike other gene therapy modalities, which require nuclear delivery, the site of action for exogenous mRNA vaccines is the cytosol where they get translated into antigenic proteins and thereby elicit an immune response. LNPs also protect the mRNA against enzymatic degradation by the omnipresent ribonucleases (RNases). Cationic nano emulsion (CNE) is also explored as an alternative and relatively thermostable mRNA vaccine delivery vehicle. In this review, we have summarized the various delivery strategies explored for mRNA vaccines, including naked mRNA injection; ex vivo loading of dendritic cells; CNE; cationic peptides; cationic polymers and finally the clinically successful COVID-19 LNP vaccines (Pfizer/BioNTech and Moderna vaccines)-their components, design principles, formulation parameter optimization and stabilization challenges. Despite the clinical success of LNP-mRNA vaccine formulations, there is a specific need to enhance their storage stability above 0 °C for these lifesaving vaccines to reach the developing world.

European Journal of Pharmaceutical Sciences, 2008

The study was aimed to optimize radiolabeling with 99m Tc, to determine the antiretroviral activi... more The study was aimed to optimize radiolabeling with 99m Tc, to determine the antiretroviral activity and to study the biodistribution of 99m Tc labeled galactosylated liposomes loaded with stavudine. Liposomes were prepared using reverse-phase evaporation method followed by extrusion through 200 nm polycarbonate membranes. The galactosylated liposomes were assessed for in vitro ligand-specific activity and the aggregation of galactosylated liposomes was found to increase as lectin concentration was increased from 5 g/ml to 30 g/ml. Free stavudine and stavudine loaded plain and galactosylated liposomes were radiolabeled with 99m Tc by direct labeling method using stannous chloride as a reducing agent. Labeling method was optimized for stannous chloride quantity to achieve maximum labeling efficiency >95%. Antiretroviral activity was determined using human immunodeficiency virus-1 (HIV) infected MT2 cell line. A dose-dependent inhibition of p24 production was observed upon treatment of HIV-1 infected MT2 cells with stavudine loaded liposomes and galactosylated liposomes. Scintigraphic imaging and quantitative biodistribution of 99m Tc labeled drug and liposomes showed that liposomal formulations were better taken up by the liver and spleen. Free drug solution was cleared from the blood. Further, a significantly higher (P < 0.05) liver and spleen retention was observed over a period of 24 h in case of galactosylated liposomes as compared to free drug and plain liposomes. Reduced uptake of the galactosylated liposomes in bone and higher and prolonged accumulation in mononuclear phagocyte system (MPS)-rich organs indicates the excellent potential of this formulation in the treatment of HIV infection.

Journal of Microencapsulation, 2009

A major problem associated with conventional leukaemia chemotherapy is the development of resista... more A major problem associated with conventional leukaemia chemotherapy is the development of resistance that can be surmounted well by combination chemotherapy. The objective of the present investigation is to report a novel technology to load two anti-leukaemic drugs of choice simultaneously inside the PAMAM dendrimer. Under optimized conditions of pH and dialysis time, one molecule of PAMAM dendrimer was found to be capable of entrapping 27.02 ± 0.51 and 8.00 ± 0.46 molecules of Methotrexate and all-trans Retinoic acid (ATRA), respectively. The simultaneous in-vitro release profiling of the loaded drugs was studied at pH 4, 7.4 and 10. The release kinetics was found to be governed by degree of dendrimer protonation, with more sustained and controlled behaviour at pH 7.4. Terminal loading of dendrimer with less haemolytic bioactive (ATRA) reduced the haemolytic toxicity of the dendrimer formulation. A cytotoxicity study was performed on HeLa cell lines by MTT assay, wherein after 72 h, the dual-drug loaded dendrimer was found to be more efficient (IC(50) 0.5 µM) as compared to that of the free drug combination (IC(50) 0.75 µM).

European Journal of Pharmaceutics and Biopharmaceutics, 2007

The aim of the present investigation was to reduce the hepatic toxicity, enhance the cellular upt... more The aim of the present investigation was to reduce the hepatic toxicity, enhance the cellular uptake and alter the pharmacokinetics of stavudine using galactosylated liposomes. β-d-1-Thiogalactopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine, which was then used to form liposomes. The galactosylated liposomal system was assessed for in vitro ligand-specific activity. The drug release from liposomes was studied by dialysis

Journal of Drug Targeting, 2007

Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as... more Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc-glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 +/- 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 +/- 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy.

Journal of Bioequivalence & Bioavailability, 2010

Journal of Drug Targeting, 2007

Nanomedicine: Nanotechnology, Biology and Medicine, 2010

Although small interfering RNA (siRNA) treatment holds great promise for the treatment of cancers... more Although small interfering RNA (siRNA) treatment holds great promise for the treatment of cancers, the field has been held back by the availability of suitable delivery vehicles. For cervical cancer the E6 and E7 oncogenes are ideal siRNA targets for treatment. The purpose of the present study was to explore the potential of dendrosomes for the delivery of siRNA targeting E6 and E7 proteins of cervical cancer cells in vitro. Optimization of dendrimer generation and nitrogen-to-phosphate (N/P) ratio was carried out using dendrimer-fluorescein isothiocyanate oligo complexes. The optimized N/P ratios were used in formulating complexes between dendrimers and siRNA targeting green fluorescence protein (siGFP). Although formulation 4D100 (dendrimer-siRNA complex) displayed the highest GFP knockdown, it was also found to be highly toxic to cells. In the final formulation 4D100 was encapsulated into dendrosomes so as to mask these toxic effects. The optimized dendrosomal formulation (DF), DF3 was found to possess a siGFP-entrapment efficiency of 49.76% +/- 1.62%, vesicle size of 154 +/- 1.73 nm, and zeta potential of +3.21 +/- 0.07 mV. The GFP knockdown efficiency of DF3 (dendrosome) was found to be almost identical to that of 4D100, but the former was completely nontoxic to the cells. DF3 containing siRNA against E6 and E7 was found to knock down the target genes considerably, as compared with the other formulations tested. Our results imply that dendrosomes hold potential for the delivery of siRNA and that a suitable targeting strategy could be useful for applications in vivo. siRNA treatment holds great promise for the treatment of cancers, but overall, the availability of suitable delivery vehicles remains a major issue. The purpose of this study was to explore the potential of dendrosomes for the delivery of siRNA targeting specific proteins in cervical cancer cells in vitro. The results suggest that dendrosomes hold potential for the delivery of siRNA and a suitable targeting strategy could be useful for applications in vivo.

Crit Rev Ther Drug Carrier Syst, 2006

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, mol... more Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site-specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system.

Vaccine, 2008

The purpose of the present research work is to explore the potential of dendrosomes in genetic im... more The purpose of the present research work is to explore the potential of dendrosomes in genetic immunization against hepatitis B. Plasmid DNA encoding pRc/CMV-HBs[S] (5.6 kb), encoding the small region of the hepatitis B surface antigen, was complexed with 5th generation poly(propyleneimine) dendrimer (PPI) in different ratios. Transfection of CHO cells revealed that a ratio of 1:50 for pDNA:PPI was optimum for transfection. Results of cytotoxicity studies showed that the toxicity of PPI-DNA complex was significantly (p < 0.05) higher for PPI 75 and PPI 100 as compared to the other PPI-DNA complexes. PPI 50 was employed for preparation of dendrosomes by reverse phase evaporation method. The dendrosomal formulation DF3 was found to possess optimum vesicle size, zeta potential and entrapment efficiency. In vitro production of HBsAg in CHO cells showed that DF3 possess maximum transfection efficiency. In vivo immunization studies were carried out by giving a single intramuscular injection of 10 g of plasmid DNA (pDNA) or its dendrimeric or dendrosomal formulation to female Balb/c mice, followed by estimation of total IgG, IgG 1 , IgG 2a , IgG 2b , biweekly. DF3 was found to elicit maximum immune response in terms of total IgG and its subclasses under study as compared to PPI 50 and pDNA at all time points. Animals immunized with DF3 developed very high cytokine level. Higher level of IFN-␥ suggests that the immune response was strictly Th1 mediated. Our observations clearly prove the superiority of dendrosomes over PPI-DNA complex and pDNA for genetic immunization against hepatitis B.

Anthropologischer Anzeiger, 2006

Pharmazie

Nanotoxicology, 2008

Nanomedicine: Nanotechnology, Biology and Medicine, 2007

Pharmaceutical Medicine, 2022

European Journal of Pharmaceutical Sciences, 2008

Journal of Microencapsulation, 2009

European Journal of Pharmaceutics and Biopharmaceutics, 2007

Journal of Drug Targeting, 2007

Journal of Bioequivalence & Bioavailability, 2010

Journal of Drug Targeting, 2007

Nanomedicine: Nanotechnology, Biology and Medicine, 2010

Crit Rev Ther Drug Carrier Syst, 2006

Vaccine, 2008