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

Abstract

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) (mPEG45-α-PLL10-PLA25) 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.

Chemical transformations during mechanoactivation of ε‐polylysine‐poly‐L‐lactic acid mixture to obtain amphiphilic copolymers

“…Similarly, PLA-PEG-PL copolymer was obtained, with methanol being used as the reaction medium for polymerization. 10 The primary NH 2 -group in PL was protected by a tert-butoxycarbonyl (Boc) group, which was removed after obtaining the final product using dichloromethane, trifluoroacetic acid, methanol, and dimethylformamide. The yield of the obtained PLA-PEG-PL copolymer was 71% (57 mg).…”

“…The yield of the obtained PLA-PEG-PL copolymer was 71% (57 mg). 10 To obtain PLA-PL statistical copolymer the authors used the joint polymerization of lactic acid anhydrosulphite and ε-N-carbobenzoxy-L-lysine-N-carboxy anhydride. 10 The process was carried out in tetrahydrofuran, using initiators of various types, at T = 50 C, for 72 h. The obtained copolymer was washed with chloroform and water, and then precipitated in petroleum ether (the yield was 67 wt%).…”

Characterization of the Interaction of Polymeric Micelles with siRNA: A Combined Experimental and Molecular Dynamics Study

“…To overcome such drawbacks, efforts have been made to obtain biocompatible polymeric architectures, serving as siRNA supports while presenting non-toxic and biodegradable features. To this end, triblock copolymeric micelles consisting of molecularly well-defined, highly pure and non-cytotoxic entities have been developed [ 10 ]. The controlled character of an optimal charge length of 10 lysines, conceptualized first by a computational method [ 11 ], helps evaluate both experimental and computational complexation efficacies.…”