Papers by Mangal Nagarsenker
Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil☆
International Journal of Pharmaceutics, Feb 1, 2007
Self-nanoemulsifying drug delivery systems (SNEDDS) were developed with the objective to overcome... more Self-nanoemulsifying drug delivery systems (SNEDDS) were developed with the objective to overcome problems associated with the delivery of cefpodoxime proxetil (CFP), a poorly bioavailable high dose antibiotic having pH dependant solubility. Solubility of CFP in oily phases and surfactants was determined to identify components of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify selected oily phases. Ternary phase diagrams were constructed to identify area of nanoemulsification for the selected systems. The influence of CFP and the pH of dilution medium on the phase behavior of selected system were assessed. The globule size of optimized CFP SNEDDS in various dissolution media was determined to check the effect of pH on its behavior. The optimized CFP SNEDDS needed surfactant content less than 40% and yielded nanoemulsion of mean globule size 170 nm, which was not affected by the pH of dilution medium. The optimized SNEDDS released CFP completely within 20 min irrespective of the pH of dissolution medium.
Indian Journal of Pharmaceutical Sciences, Mar 1, 1996
Synthesis, characterization, and in vitro evaluation of palmitoylated arabinogalactan with potential for liver targeting
Carbohydrate Research, Feb 1, 2013
Arabinogalactan (AG), a water soluble polysaccharide with more than 80 mol% galactose units, was ... more Arabinogalactan (AG), a water soluble polysaccharide with more than 80 mol% galactose units, was hydrophobized by covalent attachment of palmitoyl chains using a base-catalyzed esterification reaction with the objective of effective amalgamation of arabinogalactan in liposomes for targeting asialoglycoprotein receptors (ASGPR) on liver parenchymal cells. Palmitoylated AG (PAG) was characterized by physico-chemical parameters, IR, (1)H NMR, and (13)C NMR and molecular weight determination by gel permeation chromatography. PAG was incorporated in liposomes and the liposomes were characterized by dynamic light scattering, optical microscopy, zeta potential, and transmission electron microscopic (TEM) techniques. The liposomal system was evaluated for acute toxicity in swiss albino mice and was found to be safe. Targeting ability of PAG was confirmed by in vitro binding affinity to Ricinus communis agglutinin (RCA(120)), a lectin specific for galactose. The liposomal system with PAG was evaluated for cytotoxicity on HepG2, MCF7, and A549 cancer cell lines. Cytotoxicity study revealed enhanced activity on ASGPR-expressive HepG2 cells as compared to MCF7.
Preparation and evaluation of a liposomal formulation of sodium cromoglicate
International Journal of Pharmaceutics, 2003
Tropicamide, a mydriatic, cycloplegic drug was entrapped in liposomes. Liposomes were investigate... more Tropicamide, a mydriatic, cycloplegic drug was entrapped in liposomes. Liposomes were investigated by laser counting studies, transmission electron microscopy and differential scanning calorimetry for characterization. The precorneal clearance of liposomes was compared with solution by gamma-scintigraphy in the rabbit. The neutral liposomes failed to demonstrate significant enhancement in precorneal retention in comparison with aqueous solution. The potential of liposomes as an ophthalmic drug delivery system was investigated by comparing pupil dilatory effect of tropicamide by topical instillation, in the rabbit eye, of the solution and various drug-loaded liposomal forms, i.e. neutral liposomes, positively charged liposomes and neutral liposomes dispersed in 0.25% (w/v) polycarbophil gel. The positively charged liposomal formulation and liposomes dispersed in polycarbophil gel were found to be more effective than neutral liposomal dispersion when data were statistically treated at the 5% level of significance.
Preparation, Characterization, and Evaluation of Liposomal Dispersions of Lidocaine
Drug Development and Industrial Pharmacy, 1997
AbstractLidocaine, a local anesthetic agent, was encapsulated into liposomes employing the conven... more AbstractLidocaine, a local anesthetic agent, was encapsulated into liposomes employing the conventional lipid-film hydration technique. An attempt was made to freeze dry the aqueous liposomal dispersions. The prepared liposomal dispersions were investigated by differential scanning calorimetry (DSC), transmission electron microscopy (TEM), scanning electron microscopy (SEM), 31 P-nuclear magnetic resonance (NMR) spectroscopy, and laser counting studies for characterization. The skin partition coefficient for liposomal lidocaine was calculated. The results showed that lidocaine incorporated into the liposomes got selectively partitioned and localized in the skin to a great extent. A topical liposomal gel formulation containing 2% w/w lidocaine was prepared using Carbopol-934 as the gelling agent. The prepared formulation was tested for its local anesthetic efficacy employing the pinprick test. The liposomal preparation of lidocaine gave a much longer duration of action compared to the conventional topical ...
Stimuli-responsive micelles
Elsevier eBooks, 2018
Abstract Since they were first introduced to drug delivery a little more than three decades ago, ... more Abstract Since they were first introduced to drug delivery a little more than three decades ago, polymeric micelles have acquired a significant place among the newer drug delivery systems. From the early concept of nanoassemblies of simple di-block linear amphiphilic copolymers to the highly-evolved stimuli-responsive micelles being explored for targeted anticancer therapy, gene delivery, diagnostics, and recently for theranostic applications, polymeric micelles have traversed a long way. Stimuli-responsive polymeric micelles are derived from the family of smart polymers which show characteristic alterations in properties when subjected to specific environmental conditions, such as those of pH, temperature, photons, redox potential, ultrasound, or even enzymes. This so-called response to the stimulus, is used strategically to achieve one or more of several objectives including prevention of drug release outside of the target site, triggering of site specific or “on demand” release of therapeutic agents, increased interaction with the target cell, etc. This chapter presents a detailed review of the various classes of stimuli-responsive micelles, the strategies in their design, and the current advancement with respect to their drug delivery and diagnostic applications.
Polysaccharide conjugates surpass monosaccharide ligands in hepatospecific targeting – Synthesis and comparative in silico and in vitro assessment
Carbohydrate Research, 2021
Ligands with the polysaccharide headgroups have been recently reported by our group to possess en... more Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.
International Journal of Pharmaceutics, 2020
To investigate comparative in vitro and in vivo performance of lipid vesicular and particulate sy... more To investigate comparative in vitro and in vivo performance of lipid vesicular and particulate systems in escalating oral bioavailability for superior hepatoprotection. Materials and methods: Systems were fabricated using easy to scale up process and novel excipients to deliver Silibinin. In vitro characterization followed by pharmacokinetic and pharmacodynamic evaluation in rats was conducted to establish a correlation. Results: Nanoformulations resulted in 20 fold increase in solubilisation and significant increase in permeation. 2.5 fold increase in bioavailability was evident in vivo. Vesicles demonstrated greatest hepatoprotective potential in efficacy study. Conclusion: The findings establish a link between in vitro and in vivo performance to rank order lipid nanoartchitects. Concurrently, a significant potential in therapeutic intervention of hepatotoxicity is envisaged as elucidated.
Lecithin and PLGA-based self-assembled nanocomposite, Lecithmer: preparation, characterization, and pharmacokinetic/pharmacodynamic evaluation
Drug Delivery and Translational Research, 2016
The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites... more The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites (Lecithmer®) composed of poly(D,L-lactide-co-glycolide (PLGA) and soya lecithin. Core-shell structure of Lecithmer was evident from cryo-TEM images. Daunorubicin (DNR) and lornoxicam (LNX)-incorporated Lecithmer nanocomposites were evaluated for anticancer and anti-inflammatory activity. DNR- and LNX-loaded Lecithmer had mean particle size of ∼335 and ∼282.7 nm, respectively. Lecithmer formulated with different cationic lipids resulted in lower particle size (∼120 nm) and positive zeta potential. Entrapment efficiency of DNR and LNX was 93.16 and 88.59 %, respectively. In vitro release of DNR from Lecithmer was slower compared to PLGA nanoparticles. DNR release from Lecithmer was significantly higher at pH 5.5 (80.96 %) as compared to pH 7.4 (55.95 %), providing advantage for selective tumor therapy. Similarly, sustained release of LNX (30 % in 10 h) was observed at pH 7.4. DNR in Lecithmer showed superior cytotoxicity on human erythroleukemic K562 cells. Pharmacokinetic study in Wistar rats with i.v. administered DNR-loaded Lecithmer showed higher volume of distribution, lower elimination rate constant, and longer half-life (81.68 L, 0.3535 h(-1), 1.96 h) as compared to DNR solution (57.46 L, 0.4237 h(-1), 1.635 h). Pharmacodynamic evaluation of orally administered LNX-loaded Lecithmer showed superior anti-inflammatory activity with maximum inhibition of 81.2 % vis-à-vis 53.57 % in case of LNX suspension. In light of these results, Lecithmer can be envisaged as a promising nanosystem for parenteral as well as oral drug delivery.
Biodegradable Polymer-Based Microspheres for Depot Injection-Industry Perception
Recent Advances in Drug Delivery and Formulation
: The discovery of proteins and peptides marked the actual beginning for pharmaceutical companies... more : The discovery of proteins and peptides marked the actual beginning for pharmaceutical companies to do research on novel delivery systems for delivering these therapeutic proteins. Biodegradable polymer-based microspheres for controlled-release depot injection are known for decades and have proved to be one of the best possible approaches. Despite being known for decades, the commercial success of microsphere-based delivery systems remains limited. Very few products are seen in the market with no generics available for approved brand products whose patents have either expired or are about to expire. All this points to the complexities involved in developing these delivery systems. Still, many hurdles remain in developing these drug delivery systems namely, poor drug entrapment, unwanted burst release, poor in vitro in vivo correlation, lack of proper in vitro testing methods, problems involved during scale-up, and the most important hurdle being sterilization of the product. To achieve successful product development, all of these technical difficulties need to be simultaneously dealt with and resolved. This article attempts to highlight the problem areas for these delivery systems along with the regulatory requirements involved and map the present status of these delivery systems.
Parenteral preparations
Remington
Journal of Drug Delivery Science and Technology, 2020
Biodegradable polymers are drawing a great deal of attention in the field of nanotechnology. Albu... more Biodegradable polymers are drawing a great deal of attention in the field of nanotechnology. Albumin, abundantly present in human body, is a biocompatible and biodegradable polymer used in drug delivery systems. It is relatively an inexpensive polymer with several advantages like non-toxicity, high drug loading capacity, binding efficiency with many drugs which qualifies it as an ideal nanocarrier. The present review discusses potential of albumin nanocarriers for pulmonary application. It also discusses feasibility of employing albumin from different sources. Formulation aspects of albumin nanosystems, methods of preparation and dosage form designing are also covered. An array of excipient options suitable to be used in albumin nanocarrier system is presented. Toxicity aspects and applications of albumin nanoparticles with focus on pulmonary application are highlighted. Application of nanoparticulate structures based on albumin in delivery of drugs from category of anticancer agents, vaccines, hormones, anti-asthamatics and anti-inflammatory agents to lungs is covered. This review offers a framework for pharmaceutical scientists in designing of albumin nanoparticles for various pulmonary and systemic applications via inhalation delivery.
Indian Journal of Pharmaceutical Education and Research, 2016
Aim: To investigate potential of polymer Soluplus (SP), to form micellar/mixed micellar systems a... more Aim: To investigate potential of polymer Soluplus (SP), to form micellar/mixed micellar systems and its ability to improve solubility and consequently therapeutic efficacy of model BCS Class-II drug Lornoxicam (LNX). Methods: Soluplus based micellar systems were prepared using thin film hydration method. CMC (critical micelle concentration) was determined using two methods, namely, Iodine UV spectroscopy and Pyrene fluorescence spectroscopy. Micellar systems were characterized for their particle size, drug loading, CMC and SANS study to understand the dynamics of micellar systems. The LNX loaded micellar systems were evaluated in vivo, to evaluate their effectiveness in improving the anti-inflammatory activity of LNX in rat-paw edema model and also to observe possible reduction in ulcerogenic potential of LNX. Results: SP as well as its mixed micellar systems could effectively form stable micelles with mean diameter in range of 60-70 nm and promising LNX loading efficiency. It was e...
Journal of Controlled Release, Nov 1, 2017
Mixtures of surfactants can result in formation of various structures like micelles, vesicles and... more Mixtures of surfactants can result in formation of various structures like micelles, vesicles and inverted micelles. Catanionic vesicular systems are preferred on account of their ease of formation and thermodynamic stability. Furthermore, their charge and surfactant properties render them as useful vehicles for DNA delivery and cytotoxic compounds. They suffer from disadvantages of being leaky and yielding low encapsulation efficiencies which are averse to drug delivery purposes. Extensive efforts are being undertaken to overcome these barriers and render these vesicles amenable to spatial placement and temporal delivery of drugs. This manuscript addresses diverse aspects of catanionic vesicles including their formation, fabrication and stability. The manuscript focuses further on applications of catanionic vesicles in nanodrug delivery. Novel trends in the field of catanionics with respect to bio-compatibility and novel technologies developed using these systems have also been reviewed. An attempt has been made to compile catanionic systems reported in literature detailing surfactants and therapeutic agents employed to aid understanding and yield information of various facets that drive fabrication and potential utility of these systems in therapeutics.
Indian Journal of Pharmaceutical Sciences, 2010
Dixit, et al.: Simultaneous RP-HPLC Determination of Simvastatin and Ezetimibe A simple, specifi ... more Dixit, et al.: Simultaneous RP-HPLC Determination of Simvastatin and Ezetimibe A simple, specifi c and sensitive reverse phase high performance liquid chromatographic method was developed and validated for simultaneous determination of ezetimibe and simvastatin from pharmaceutical dosage forms. The method uses C18 ODS Hypersil column and isocratic elution. The mobile phase composed of acetonitrile:phosphate buffer (pH 4.5, 0.01M) in the ratio of 65:35 v/v was used at a fl ow rate of 1.0 ml /min. UV detector was programmed at 232 nm for fi rst 10 min and at 238 nm for 10 to 20 min. All the validation parameters were in acceptable range. The developed method was effectively applied to quantitate amount of ezetimibe and simvastatin from tablets. The method was also applied suitably for determining the degradation products of ezetimibe and simvastatin.
Nanomedicine: Nanotechnology, Biology and Medicine, Oct 1, 2017
Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore,... more Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore, we assessed the improved antimicrobial and antibiofilm activity of Levofloxacin (LFX) and Serratiopeptidase (SRP) combinations in in vitro microbiological studies. Further, pharmacodynamic and pharmacokinetic studies of liposomal LFX in combination with SRP (LFX liposome-SRP) were performed in S. aureus infected rats. LFX at sub-MIC with SRP eradicated >90% of the preformed biofilm. The entrapment efficiency of LFX in liposome was >80% and the co-spray dried product had MMAD <5 µ. We observed high LFX concentration in the lung (3.39 µg/ml over 3 h) and AUC/MIC ≥100. In a pharmacodynamic study, untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels and microbial load compared to control. Conversely, LFX liposome-SRP significantly abated these adverse repercussions. Histological findings were also in agreement with these observations. Furthermore, our findings corroborate exhibited improved antibiofilm and antimicrobial efficacy of LFX liposome-SRP in treating S. aureus infection.
Advanced Drug Delivery Reviews, 2020
Highlights • Liposomes and their related constructs offer unique advantages in terms of drug and ... more Highlights • Liposomes and their related constructs offer unique advantages in terms of drug and vaccine delivery. • However, current processes used for the manufacture of liposomes present a range of challenges, driving up cost, and limiting production. • New production methods can address these issues and support the cost-effective manufacture of current liposomal systems and facilitate the development of new liposomal products.
Polysaccharide and monosaccharide guided liver delivery of Sorafenib Tosylate – A nano-strategic approach and comparative assessment of hepatospecificity
International Journal of Pharmaceutics, Sep 1, 2022
Journal of Pharmaceutical Sciences, Oct 1, 2019
Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties... more Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT 3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeability" and can therefore be classified as a BCS class I drug. Furthermore, ondansetron hydrochloride 8 mg IR tablets (Zofran ® 8 mg) and multiples thereof (16 mg ¼ Zofran ® 8 mg  2 tablets and 24 mg ¼ Zofran ® 8 mg  3 tablets) meet the criteria of "rapidly dissolving" in dissolution testing. Ondansetron hydrochloride has a wide therapeutic window and is well-tolerated after oral administration. Based on its favorable physicochemical properties, pharmacokinetic data and the minimal risks associated with an incorrect bioequivalence decision, the BCS-based biowaiver procedure can be recommended for ondansetron hydrochloride dihydrate IR tablets.
Osteoporosis is a systemic skeletal disease affecting postmenopausal women worldwide. Adverse sid... more Osteoporosis is a systemic skeletal disease affecting postmenopausal women worldwide. Adverse side effects are associated with long term conventional hormone therapy in osteoporosis treatment. Estradiol was loaded in PLGA nanoparticles coated with polyethylene imine to impart positive surface charge to preferentially localize hormone in the negative surface of bone environment evading unwanted side effects. Nanoparticles prepared by emulsion solvent evaporation method were smaller than 200 nm with a surface charge of 35mV. In vitro hydroxyapatite binding studies revealed superior binding of 82% by polycationic particles compared to meagre 28% by plain PLGA nanoparticles. In vivo biodistribution studies in mice displayed nearly 3 fold higher bone uptake by cationic nanoparticles compared to plain PLGA system at 24 hours. Hematological and histological evaluation in acute toxicity study showed safe and nontoxic nature of cationic nanoparticles.. Higher C max, AUC 0-inf, t1/2 values an...
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Papers by Mangal Nagarsenker