Polyethylene sebacate doxorubicin nanoparticles: role of carbohydrate anchoring on in vitro and in vivo anticancer efficacy

Drug Delivery
Sandhya PranatharthiharanPadma V Devarajan

Abstract

We report carbohydrate-anchored polyethylene sebacate (PES)-Gantrez® AN 119 Doxorubicin hydrochloride (Dox) nanoparticles (NPs) for enhanced anticancer efficacy. The carbohydrates Arabinogalactan (AGn), an adjuvant in anticancer chemotherapy and pullulan (Pul) reported to promote collagen synthesis, were selected as ligands. PES Dox NPs of an average size around 200 nm, greater than 20% w/w Dox loading and negative zeta potential were anchored with Pul, AGn, and Pul-AGn combination by simple incubation. Increase in particle size and zeta potential confirmed carbohydrate anchoring. FTIR confirmed ionic complexation of Dox and Gantrez® AN 119. DSC and XRD demonstrated amorphization of Dox. Higher Dox release in pH 5.5 as compared with pH 7.4 is beneficial for reduced systemic toxicity and enhanced drug release in tumors. Good in vitro serum stability and low hemolysis revealed suitability for intravenous administration. All NPs revealed circulation longevity in normal rats. Pul NPs revealed superior anticancer efficacy in vitro and an 11-fold enhancement in uptake in MCF-7 breast cancer cells. The greater efficacy in vivo is attributed to possible pullulan-mediated integrin receptor uptake and interaction with tumor collagen. His...Continue Reading

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