Add time:09/30/2019         Source:infona.pl

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.

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