Dehydroascorbate-derivatized chitosan particles for targeting antimalarial agents to infected erythrocytes

Publication date: 30 May 2017 Source:International Journal of Pharmaceutics, Volume 524, Issues 1–2 Author(s): Hasham Shafi, D.V. Siva Reddy, Tabassum Khan, Rajeev Ranjan, Ashish Srivastava, Suniti Vaishya, Tanuj Sharma, Mohammad Imran Siddiqui, Saman Habib, Amit Misra The mammalian glucose transporter GLUT-1 and Plasmodium falciparum hexose transporter PfHT1 are overexpressed on human RBC infected with the parasite (iRBC), presumably for enhanced glucose uptake. Dehydroascorbic acid (DHA) competes out glucose in GLUT-1 binding. We prepared particles containing chloroquine phosphate using novel derivatives of chitosan (CSN). CSN was either pre-derivatized with DHA (PRE) or particles made of CSN were derivatized by surface-grafting DHA (POST). The optimized formulations were analyzed for size (170–200nm) drug content (about 40%) entrapment efficiency (50–57%), in vitro drug release (80% in 72h, Higuchi’s model), hemolysis on exposure to whole blood or RBC at 5% hematocrit, cytotoxicity towards cultured HEK 293T (kidney) and HepG2 (hepatic) cells, targeting iRBC and in vitro efficacy against P. falciparum. PRE particles were superior to POST CSN particles in terms of uptake and extent of preferential targeting to iRBCs than RBCs. Unlike starch particles reported earlier, dextrose did not competitively inhibit uptake of DHA-derivatized CSN particles. Both formulations significantly induced parasite inhibition at 1nM while free drug showed comparable activity ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research