Synthesis of novel polymeric nanoparticles (methoxy-polyethylene glycol-chitosan/hyaluronic acid) containing 7-ethyl-10-hydroxycamptothecin for colon cancer therapy: in vitro, ex vivo and in vivo investigation

Abstract

The goal of the current study was to target 7-ethyl-10-hydroxycamptothecin (SN38) orally to colon tumours by synthesizing a targeting polymer. To achieve the optimum delivery for SN38, initially methoxy-polyethylene glycol (mPEG)-chitosan was synthesized and then nanoparticles were developed through ionic gelation between mPEG-chitosan and hyaluronic acid as a ligand for cell-surface glycoprotein CD44 receptor. The SN38 was loaded in nanoparticles (SN38-NPs) using the non-covalent physical adsorption method. The size of the optimized SN38-NPs was 226.7 nm, encapsulation efficiency was 89.23% and drug content was 7.98 ± 0.54% in the optimum formulation. The attachment of mPEG to chitosan was confirmed by proton nuclear magnetic resonance. The results of differential scanning calorimetry and Fourier transforms infra-red analysis indicated that SN38 existed in amorphous form and functional groups of SN38 protected in the formulations which could be a sign of suitable encapsulation of SN38 in SN38-NPs. In vitro study indicated that SN38-NPs were more potent against the cancer cells than free SN38. The cellular uptake of SN38-NPs improved up to 1.6-fold against human colorectal adenocarcinoma (Caco-2) cells. Moreover, SN38-NPs remarkably demonstrated superior anti-tumor efficacy in contrary to pure SN38. This suggests the advantage of SN38-NPs as a potent oral drug carrier which could be further explored for clinical investigations.