Parthasarathi K. Kulkarni

Microsponges based novel drug delivery system for augmented arthritis therapy

The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug–polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug–polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.

Recent Advances in Nanosystems and Strategies for Managing Leishmaniasis.

BACKGROUND Parasitic infection such as leishmaniasis, a neglected tropical disease, presents a significant global burden which is responsible for high mortality rate especially in less developed countries. Its intracellular nature and disseminated locations of parasite, limited number of chemotherapeutic agents, increasing incidences of resistance to first line drugs and toxicities, pose a great challenge to formulation scientists that have necessitated effective management of leishmanial infection by modulating the delivery of existing drugs. Over the past decade, research on development of alternative treatments such as nanotechnology-based drug delivery systems (nanoparticles, nanosuspensions, liposomes etc.), use of natural products as well as development of antileishmanial vaccine has been extensively investigated. OBJECTIVE The present review focuses on different facets of therapeutic strategies, existing miscellaneous drug delivery systems and approaches intended for management, as well as treatment of the infection, with an objective to summarize the current trends and strategies adopted for antileishmanial therapy in a systematic manner. Moreover, the article encloses an eclectic collection of patents allied to new-fangled chemotherapeutics for antileishmanial therapy. CONCLUSION The reported miscellaneous novel drug delivery systems along with the diverse approaches are seem to be precise, secure and relatively effective; and in an outcome, could lead to the new track for management of leishmaniasis.

A 32 full factorial design for development and characterization of a nanosponge-based intravaginal in situ gelling system for vulvovaginal candidiasis

Clotrimazole (CTZ) is a Biopharmaceutics Classification System (BCS) Class II drug having a limited therapeutic potential because of its poor aqueous solubility and relatively short half-life. The rationale behind the present research effort was to enhance the solubility and efficacy of CTZ by having it form a complex with hydroxypropyl β-cyclodextrin (HP-β-CD) nanosponges. Nanosponges (NSs) are hyper-cross linked cyclodextrin polymer-based colloidal structures with three-dimensional networks. Herein, NSs were prepared using dimethyl carbonate as a cross linker, suitably gelled, and were assessed for in vitro release, in vitro bioadhesion, in vivo antifungal activity and in vivo irritation using female Wistar albino rats. Nine formulations were prepared based on a 32 full factorial design using different Pluronic F-127: Pluronic F-68 ratios. The prepared CTZ-HP-β-CD NS samples were characterized by carrying out SEM, TEM, and FT-IR spectroscopy studies, as well as DSC and XRPD studies. The average particle size of loaded NS (N6) was found to be 455.6 nm. This sample displayed the lowest polydispersity index of the samples tested, and displayed a high zeta potential (−21.32 ± 1.3 mV), indicative of a stable colloidal nanosuspension. The optimized CTZ NS-based in situ gel (F-10) demonstrated prolonged drug release (up to 15 h), considerably longer than that of the conventional in situ gel, whose drug release only lasted for less than 6 h. The CTZ-NS gel showed higher in vivo antifungal activity and in vitro bioadhesion than did the conventional in situ gel. Furthermore, in vivo irritation studies showed the optimized CTZ NS gel formulation to be a non-irritant. All of these results signified the promising applicability of the formulated CTZ NS gel as a novel delivery system for the local treatment of vaginal candidiasis and other similar infections.

Nanosponge Carriers- An Archetype Swing in Cancer Therapy: A Comprehensive Review.

Nanotechnology and nanomedicines are emerging research meadows; which chiefly focuses on creating and manipulating materials at a nanometer level for the betterment in imaging, diagnosis and treatment of a range of diseases together with cancer. Cyclodextrin-based nanosponges, anticipated as a new-fangled nanosized delivery system, are ground-breaking hyper-crosslinked cyclodextrin polymers nanostructured within a three-dimensional network. Nanosponges based systems hold the potential of elevating the solubility, absorption, penetration, bioavailability, in vivo stability, targeted as well as sustained delivery, and therapeutic efficiency of numerous anticancer agents. The extension of nanosponges based drug delivery systems is an exhilarating and demanding research pasture, predominantly to overcome aforementioned problems allied to existing anticancer formulations and for the further progressions in cancer therapies. Nanosponges in cancer therapy, particularly cyclodextrin based nanosponges are brought up in this review. By quoting diverse attempts made in pertinent direction, efforts have been made to exemplify the characteristics, suitability and versatility of cyclodextrin based nanosponges for their promising applications in cancer treatment.

Current Perspectives on Novel Drug Delivery Systems and Approaches for Management of Cervical Cancer: A Comprehensive Review

Cervical cancer is uterine cervix carcinoma, the second deadly cancer and has a high incidence and mortality rate. In the developing world conventional treatment strategies such as surgical intervention and chemoradiotherapy are less widely available. Currently cancer research focuses on improving treatment of cervical cancer using various therapies such as gene therapy, recombinant protein therapy, photodynamic therapy, photothermal therapy and delivery of chemotherapeutic agents using nanoparticles, hydrogel and liposomal based delivery systems and also localized delivery systems which exist in a variety of forms such as intravaginal rings, intravaginal patches, intravaginal films, etc. in order to improve the drug delivery in a controlled manner to the diseased site thereby reducing systemic side effects. The present review encloses existing diverse delivery systems and approaches intended for treatment of cervical cancer.

The effect of nanonization on poorly water soluble glibenclamide using a liquid anti-solvent precipitation technique: aqueous solubility, in vitro and in vivo study

The aim of the present research was to improve the aqueous solubility and oral bioavailability of glibenclamide (GLB), a BCS class-II drug. A GLB nanosuspension (NS) was prepared using a liquid anti-solvent (LAS) precipitation technique and stabilized using HPMC K15M and lactose. Different in-process variables which directly affect the precipitated particle size have been thoroughly studied and optimized. The effect of a cryoprotective agent which could prevent agglomeration during lyophilisation was investigated. The optimal formulations of GD-H0.3d and GD-H0.4f exhibited a size range of 168.6 and 342.2 nm respectively and did not show any interaction when screened for incompatibility using FT-IR and DSC, but exhibited a decrease in crystallinity. The prepared GLB NPs exhibited superior aqueous solubility and dissolution when compared to pure GLB. The oral bioavailability of optimized formulations was found to exhibit 2.59, 1.67, 1.19, 2.50 and 2.40 folds of increment with respect to Cmax, Kel (h−1), t1/2, AUC0–24 h and AUC0–∞ for GD-0.3d in contrast to pure GLB.

Cyclodextrin Nanosponges in Drug Delivery and Nanotherapeutics

The drug delivery technology landscape has become highly competitive and rapidly evolving as more and more developments in delivery systems are being integrated to optimize the efficacy and cost effectiveness of therapy. Currently, extensive research in the field of nanotechnology and nanomedicines is ongoing with a major focus towards manipulating materials at nanoscale; which can subsequently lead to advancements in diagnosis, imaging as well as treatment of a broad spectrum of diseases. In wake of recent findings, cyclodextrin based nanosponges comprising of hyper-crosslinked cyclodextrin polymers, are trendsetting in modern times with nanostructured three-dimensional network. Nanosponges based systems can address the issues related to solubility, absorption, penetration, bioavailability, in vivo stability, and can achieve sustained and targeted delivery with maximum therapeutic efficacy for a number of pharmaceutical entities. Molecules having molar mass between 100 and 400 Da, and with less than five condensed rings can be easily entrapped into nanocavities. For synthesizing nanosponges, melt method, solvent method, quasi-emulsion solvent diffusion, ultrasound and microwave assisted method can be adopted. Nanosponges synthesized via microwave method exhibits narrow size distribution, and higher crystallinity and drug loading (~2 fold) than the counterparts synthesized via conventional methods. Among diverse types, carbamate nanosponges have notable ability of binding to the organic molecules with loading capacity of 20–40 mg per cm3, and ~84% of dissolved organic carbon can be taken away from waste water; hence mostly used for water purification. However, polarity and flexible dimensions are the distinct features of carbonate nanosponges, and via synthetic reaction under different conditions, carbonate nanosponges can be obtained in amorphous or semi-crystalline form. Ester nanosponges have ability to host apolar organic molecules together with the cations, owing to presence of free polar carboxylic group. Lately, stimuli-responsive, intelligent or smart polymeric nanosponges have also been proposed for controlled delivery of low molecular weight and macromolecular drugs. In all, cyclodextrin nanosponges based drug delivery systems have achieved two to tenfolds improved stability, four to 25-folds enhanced solubility and three to fivefolds increased drug targeting efficiency; when compared to direct injection. The extension of nanosponges based drug delivery systems is an exhilarating and demanding research pasture, predominantly to overcome problems allied to existing formulations and for the further progressions in the field of pharmaceutical sciences and technology. Herein, nanosponges has been extensively reviewed as novel nanocarrier and adjunct with an all-inclusive focus on the suitability, versatility and characteristics of cyclodextrin based nanosponges for the promising applications in the fields of drug delivery and nanotherapeutics. Additionally in this chapter, development of nanosponges with a major focus on cyclodextrin based nanosponges has been well covered, and special importance has been given on discussing the preparation methods, characterization techniques and prominent applications of these novel drug delivery carriers for therapeutic purposes.

Cyclodextrin-based nanosponges in drug delivery and cancer therapeutics

Abstract In recent years, research in the field of nanotechnology and nanomedicines has become ever more predominant, and specially focuses toward tailoring and manipulating materials at nanometer level for their imperative applications in diagnosis, imaging as well as treatment of wide range of diseases. Cyclodextrin (CD)-based nanosponges (NSs) have recently emerged as potential front-runners in the field of nanotechnology, and have received important relevance in agro science, pharmaceutical, biomedical, and biotechnological applications. A number of NSs-based drug delivery systems with different types of CDs and crosslinkers have been developed over the past decade, depending upon the specific applications of the same. The technology has majorly contributed toward achieving foremost prerequisites such as solubility, stability, sustained release, enhancement of permeability and bioavailability, improved activity and also aided in enabling proteins and peptides delivery, stimuli-sensitive drug release and ocular delivery, etc. The extent of research in developing NSs-based drug delivery systems has turn out to be exhilarating and demanding; chiefly to master the countless hurdles associated with existing anticancer formulations, and also for further advancements in cancer therapies. The present chapter captures and structures a comprehensive outlook of the state-of-art of NS technology aided cancer therapeutics that have been revealed till date. By describing numerous attempts made in this direction, efforts have been made to illustrate the suitability and versatility of CD-based NSs for their propitious applications in cancer therapy. This writing will also render an ideal stage for formulation scientists, biologists, and cancer scientists, for understanding the current trends and progress of CD-based NSs in drug delivery and cancer therapeutics.

Cyclodextrin nanosponge-based systems in drug delivery and nanotherapeutics: Current progress and future prospects

Abstract In recent times, nanotechnology and nanomedicines have been researched with a major focus on manipulating materials at nanometer level that can bring about advances in imaging, diagnosis, as well as treatment of a broad spectrum of diseases. Cyclodextrin (CD)-based nanosponges (NSs), foreseen as modern nanosized delivery systems, are trendsetting hypercross-linked CD polymers that are nanostructured within a three-dimensional network. Nanosponge-based delivery systems inherit the potential for enhancing the solubility, absorption, penetration, bioavailability, in vivo stability, sustained and targetable delivery, and therapeutic efficiency of numerous pharmaceutical agents. The system predominantly and effectively addresses the aforementioned problems related to the existing formulations, with further advancements in the field of pharmaceutical sciences and technology. In this chapter, NSs are scrutinized as novel nanocarrier and adjuncts, with an all-inclusive focus on the characteristics, suitability, and versatility of CD-based NSs for their promising applications in drug delivery and nanotherapeutics.