Biomedical subjects

S Bhadra

Publications and source records attributed to S Bhadra.

At least 19 recordsLinked to original sources

PubMed2006

PEGylated peptide dendrimeric carriers for the delivery of antimalarial drug chloroquine phosphate.

PURPOSE: The present study was aimed at developing and exploring the use of uncoated and chondroitin sulfate A (CSA) coated PEGylated poly-L-lysine-based dendrimers for controlled and sustained delivery of a blood schizonticide, chloroquine phosphate (CQ). METHODS: The poly-L-lysine-based peptide dendrimers with PEG amine core prepared and coated with CSA were used to encapsulate the drug molecules by dialysis method. Effect of CSA coating on the surface characteristics, drug entrapment, drug release, stability, hemolytic toxicity, macrophageal interactions, and cytoadherence were determined and compared with those of uncoated systems. RESULTS: The CSA coating of the carriers was found to increase size and drug loading capacity, and reduce drug release rate and hemolytic toxicity. Transmission electron microscopic study revealed the surface properties of the systems. Stability studies had shown increased stability of the formulations on CSA coating. There was a significant reduction in hemolytic toxicity and cytotoxicity of CQ by the present dendrimeric carriers, which became more prominent on further CSA conjugation of the equivalent drug-loaded dendrimeric carriers. There were also significant reduction in levels of ring and trophozoite stages of Plasmodium falciparum in liquid culture when treated with CSA coated dendrimers because of the expression of similar carbohydrate receptors as that by placental and cerebral barriers for infected red blood cells. The systems were also found suitable for prolonging and controlling the blood level of drug as indicated by blood level and organ distribution studies in albino rats on intravenous administration, precluding any significant hematological or toxicological manifestations. CONCLUSION: Thus it can be said that CSA coating can improve drug-loading capacity, control and sustain the release of CQ from such carriers, and can suitably act as safer and effective carriers for intravenous CQ administration.

Animals↗

PubMed2005

Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting.

In the present study it was intended to deliver primaquine phosphate (PP), a liver schizonticide directly to liver cells using polypropyleneimine (PPI) dendrimers-coated peripherally with galactose. PPI dendrimers were synthesized by consecutive Michael double addition reaction (using ethyelenediamine as core), followed by hydrogenation reaction. Galactose conjugation was carried out by ring opening reactions, followed by Schiff's reaction and reduction to secondary amine in sodium acetate buffer (pH 4.0). IR, NMR, MASS spectroscopy were used for the confirmation of synthesis of uncoated and coated dendrimers. The formulations were made by equilibrium dialysis of dendrimers with the solution of PP. Then the formulations were characterized by TEM for size and shape. Release rate, hemolytic toxicity; bio-distribution and blood level studies were also performed on lyophilized formulations. The results obtained indicated that galactose coating of PPI systems increases the drug entrapment efficiency by 5-15 times depending upon generations. Galactose coating prolonged release up to 5-6 days as compared to 1-2 days for uncoated PPI systems. The hemolytic toxicity, blood level and hematological studies proved these systems to be safer and suitable for sustained drug delivery. Blood level studies proved the suitability of the systems for the prolonged circulations and delivery of PP to liver. The galactose coating of PPI dendrimers can therefore make the PPI systems more effective and suitable for targeted delivery of Primaquine phosphate to liver.

Animals↗

PubMed2005

Chitosan hydrochloride based microspheres of albendazole for colonic drug delivery.

Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver albendazole specifically into the colon. Microspheres were prepared by an emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration, stirring rate and concentration of cross-linking agent on the particle size and drug loading was studied. With an increase in CH concentration, the average particle size was increased. Increased agitation speed reduced the size of the microspheres but higher agitation speed resulted in irregularly shaped microspheres. Increasing the concentration of cross-linking agent produced more regularly shaped microspheres of smaller size. The drug loading was highest at a drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of cross-linking agent. The effect of CH concentration on in vitro drug release from the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro drug release study of the optimized formulation was carried out in simulated colonic fluid, with and without 2% rat caecal content. The drug release in 24 h was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid with rat caecal contents.

Albendazole↗

PubMed2003

A PEGylated dendritic nanoparticulate carrier of fluorouracil.

The present study was aimed at developing and exploring the use of uncoated and PEGylated newer PAMAM dendrimers for delivery of anti-cancer drug 5-fluorouracil. For this study, successive Michael addition and exhaustive amidation reactions were used to synthesize 4.0 G PAMAM dendrimers, using ethylenediamine as core and methylmethacrylate as propagating agent. The dendrimer was PEGylated using N-hydroxysuccinimide-activated carboxymethyl MPEG-5000. IR and NMR data proved the synthesis. Various physicochemical parameters, SEM, TEM, lambda(max) values, hemolytic toxicity, drug entrapment, drug release and blood-level studies of both PEGylated and non-PEGylated systems were determined and compared. The PEGylation of the systems was found to have increased their drug-loading capacity, reduced their drug release rate and hemolytic toxicity. TEM study revealed surface properties of the systems. Stability studies had shown its stability at room temperature in dark. The systems were found suitable for prolonged delivery of an anti-cancer drug by in vitro and blood-level studies in albino rats, without producing any significant hematological disturbances. PEGylation has been found to be suitable for modification of PAMAM dendrimers for reduction of drug leakage and hemolytic toxicity. This, in turn, could improve drug-loading capacity and stabilize such systems in body. The study suggests use of such PEGylated dendrimeric systems as nanoparticulate depot type of system for drug administration.

Animals↗

PubMed2002

Pegnology: a review of PEG-ylated systems.

Polyethylene glycol conjugation or linking with the system is called PEGylation. Many novel drug systems are used for the delivery of drugs and bioactive substances to particular sites in a controlled or sustained manner, but various side effects or shortcomings restrict their use for the intended purpose. The shortcomings such as RES uptake, drug leakage, immunogenicity, stability, hemolytic toxicity etc. can generally be overcome by PEGylation of novel drug delivery systems such as liposomes, proteins, enzymes, drugs, nanoparticles etc. In this article the whole aspect of PEGylation starting from activation and derivatisation of poly (ethylene glycol) to the linking and designing of systems and their purification and characterization is discussed. The various properties of Pegylated systems are also discussed.

Animals↗

PubMed1995