Three‐Layered Biodegradable Micelles Prepared by Two‐Step Self‐Assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA Triblock Copolymers as Efficient Gene Delivery System

Abstract

"Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.

Synthesis and characterization of polylactide‐PAMAM “Janus‐type” linear‐dendritic hybrids

“…No precipitation is observed in the chloroform‐ d solution, which suggests the formation of a reverse‐micelle where PAMAM is shielded from the solvent (i.e., micelle core) and PDLLA acts as a stabilized shell. Such analyses have been reported by others to give indirect confirmation of a covalently linked copolymer with both hydrophilic and hydrophobic components …”

Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon

“…For this purpose, related articles have been taken on web of science and pubMed sites, and out of 470 applied papers, 35 recent in vivo studies have been selected for further analysis. It is hoped that this article will create new insights and clinical efforts [12]. Over the years, many polymer vectors have been studied.…”

Characterization and Optimization of PLA Stereocomplexed Hydrogels for Local Gene Delivery Systems

“…Regenerated cellulose dialysis tube with MWCO (3.5–5k) was purchased from Spectrum Labs (Rancho Dominquez, CA, USA). The purification and storage procedures for all monomers, catalyst, macroinitiators and solvents used in this study can be found in our previous reports [29,31].…”

“…In our previous work, the combination of triblock copolymers, PLLA-PEI-PLLA and PLLA-PEG-PLLA, has shown to produce nano-sized three-layered micelles (3LM), where the DNA/PEI polyplex is localized within a hydrophobic capsule [31]. The 3LM with relatively less toxic low MW linear-PEI has incorporated high concentrations of DNA.…”