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Due to the lack of safe carriers for the delivery of small interfering RNA (siRNA), clinical applications of nucleotide-based therapeutics have been limited. In this study, biodegradable amphiphilic triblock copolymers with tailored molecular weights for each block composed of methoxy poly(ethylene glycol) (2000 g/mol), poly( L -lysine) (1300 g/mol) and poly( D , L -lactic acid) (1800 g/mol) (mPEG 45 -α-PLL 10 -PLA 25 ) were synthesized and fully characterized. The peptide synthesis was carried out on a solid phase to limit the presence of cationic charges. The arrangement and availability of cationic amino groups within a micellar vector were investigated to determine the colloidal stability as well as the predisposition of these systems to vectorize siRNAs in addition to their already known ability to improve the solubility of hydrophobic compounds. For this purpose, a triblock copolymer containing an  epsilon  poly( L -lysine) was synthesized similarly. Accordingly, the arrangement of the cationic segment modifies the rigidity involving a complexation constraint due to limited cationic charges available on the surface, which can compromise the efficiency of delivery into cells. In addition, the two vectors were biocompatible in different human cell lines.

Comparison of triblock copolymeric micelles based on α- and ε-poly(L-lysine): a Cornelian choice