Nanoparticulate delivery of irinotecan active metabolite (SN38) in murine colorectal carcinoma through conjugation to poly (2-ethyl 2-oxazoline)-b-poly (L-glutamic acid) double hydrophilic copolymer.

Nanoparticulate delivery of irinotecan active metabolite (SN38) in murine colorectal carcinoma through conjugation to poly (2-ethyl 2-oxazoline)-b-poly (L-glutamic acid) double hydrophilic copolymer. Eur J Pharm Sci. 2019 May 25;: Authors: Salmanpour M, Yousefi G, Samani SM, Mohammadi S, Anbardar MH, Tamaddon A Abstract SN-38 is the active metabolite of irinotecan, an FDA-approved chemotherapeutic agent indicated for colorectal carcinoma, which would not be clinically applicable due to its very poorly soluble and hydrolytic degradation properties. To overcome these limitations, it was proposed to conjugate SN38 to residing carboxylic acid residues in poly (2-ethyl 2-oxazoline) block poly (L-glutamic acid), inducing nano-assembly in aqueous medium. Following a series of reactions including poly (2-ethyl oxazoline) macro-initiated ring opening polymerization of N-carboxyanhydride, deprotection of benzyl group and chemical conjugation of SN38 via biodegradable ester linkage, the as-synthesized product was characterized by dynamic light scattering, ζ potential and transmission electron microscopy. The resulting particles presented about 90% loading efficiency with a mean size of 90 nm. Upon incubation with colorectal carcinoma CT26 cell line, higher association of SN-38 fluorescence and significantly more specific cytotoxicity was noticed for the SN38 conjugated particles than free drug. Therapeutic applicability of the as-synthesized...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research