Sahil Kumar

Nanogel—an advanced drug delivery tool: Current and future

Nanogels are robust nanoparticles that could be used to deliver active drug compounds in controlled drug delivery applications. Nanogels drug delivery system is more effective and safer for both hydrophilic and hydrophobic drugs due to their chemical composition and formulations that are inappropriate for other formulations. Nanogels have enabled enlargement of functionalized nanoparticles, which act as a drug carriers that can be loaded with drugs and other active material to be released in a controlled manner at specific site. This review aims at providing general introduction on nanogels, recent synthesis methodology and their novel application in different fields.

Design, synthesis and evaluation of antimalarial potential of polyphosphazene linked combination therapy of primaquine and dihydroartemisinin

Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, (1)H NMR, (31)P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35days without any recrudescence, thus proving to be effective against resistant malaria. The study provides an alternative combination regimen found to be effective in the treatment of resistant malaria.

Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria

Abstract Malaria is a major public health problem all over the world, particularly in tropical and subtropical countries due to the development of resistance and most deadly infection is caused by Plasmodium falciparum. There is a direct need for the discovery of new drugs with unique structures and mechanism of action to treat sensitive and drug-resistant strains of various plasmodia for radical cure of this disease. Traditional compounds such as quinine and related derivatives represent a major source for the development of new drugs. This review presents recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to novel active molecules which are under clinical trials. The review also encompasses the other heterocyclic compounds emerged as potential antimalarial agents with promising results such as acridinediones and acridinone analogues, pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives, biscationic choline-based compounds and polymer-linked combined antimalarial drugs are also discussed. At last brief introduction to heterocyclics in natural products is also reviewed. Most of them have been under clinical trials and found to be promising in the treatment of drug-resistant strains of Plasmodium and others can be explored for the same purpose.

Synthesis and in vitro drug release studies on substituted polyphosphazene conjugates of lumefantrine.

The present study pertains to the delivery of antimalarial drug (Lumifantrine). In this, polyphosphazene has been used in the synthesis of polyphosphazene-linked conjugates of Lumifantrine. These polymer-linked Conjugates have been synthesized and characterized by modern analytical techniques. The in-vitro drug release of Lumifantrine drug conjugates: p -Amino benzoic acid ester substituted polyphosphazene drug conjugate (15) and Glycine methyl ester substituted polyphosphazene drug conjugate (21) have been found to be 6.00 % and 5.96% (pH 1.2), 88.52% and 79.86% (pH 7.4), respectively. These drug conjugate may prove an effective delivery system for the treatment of malaria.

Recent advancesin the development of novel drug delivery systems for the prophylaxis of malaria

The present review high-lights the advancement in nanoparticles formulations for the prophylaxis of malaria. An attempt has been made to describe various novel drug delivery systems based on approaches such as polymeric, metallic, natural, chitosan/antisense (AS) and chitosan/sense (S) oligodeoxynucleotide based nanoparticles etc. for the treatment of malaria. The polymer such as chitosan, hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone; the metal like gold and silver and other carriers such as glyceryl-dilaurate, albumin etc. have been explored for the development of novel nanoparticles formulations. These developed nanoparticles formulation have improved the targeted drug delivey of various clinically used antimalarial therapeutic agents such as hydroxychloroquine, curcumin, artemisinin, artemether and lumefantrine etc.

Drug targets for resistant malaria: Historic to future perspectives

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria.