Poly(aspartic acid)-block-polylactide diblock copolymers (PAsp-b-PLAs) having both hydrophilic and hydrophobic segments of various lengths were synthesized. These PAsp-b-PLA diblock copolymers formed polymeric micelles consisting of a hydrophobic PLA core and a hydrophilic, pH-sensitive PAsp shell in aqueous solution. The effects of the segment length of both the PLA and the PAsp portions and the pH of the solution on the shapes and sizes of the PAsp-b-PLA polymeric micelles were investigated. The results indicated a balance between the effects of electrostatic repulsion, hydrogen bonding in the PAsp shell layer, and hydrophobic interactions in the PLA core determine the sizes of the PAsp-b-PLA polymeric micelles. Moreover, the PAsp-b-PLA polymeric micelles did not possess any cytotoxic activity against L929 fibroblast cells. The obtained polymeric micelle should be useful for biodegradable biomedical materials such as drug delivery vehicle.

Partially cholesterol‐substituted 8‐arm poly(ethylene glycol)‐block‐poly(L‐lactide) (8‐arm PEG‐b‐PLLA‐cholesterol) has been prepared as a novel star‐shaped, biodegradable copolymer derivative. The amphiphilic 8‐arm PEG‐b‐PLLA‐cholesterol aqueous solution (polymer concentration, above 3 wt%) exhibits instantaneous temperature‐induced gelation at 34 °C, but the virgin 8‐arm PEG‐b‐PLLA does not, irrespective of concentration. Moreover, an extracellular matrix (ECM)‐like micrometer‐scale network structure has been created with favorable porosity for three‐dimensional proliferation of cells inside the hydrogel. This network structure is mainly attributed to specific self‐assembly between cholesterol groups. The 10 and 20 wt% hydrogels are eroded gradually in phosphate buffered saline at 37 °C over the course of a month, and after that the gel becomes completely dissociated. Moreover, L929 cells encapsulated into the hydrogel are viable and proliferate three‐dimensionally inside the hydrogels. Thus, in‐vitro cell culture studies demonstrate that 8‐arm PEG‐b‐PLLA‐cholesterol is a promising candidate as a novel injectable cellular scaffold.

Biodegradable poly(a-malic acid) (7) was synthesized by means of ring-opening homopolymerization of malide dibenzyl ester (9, which is a cyclic dimer of b-benzyl malate. In order to obtain a high-molecular-weight biodegradable lactic acid type polyester having pendent modifiable groups, ring-opening copolymerization of malide dibenzyl ester with L-dilactide was applied to give poly(a-malic acid-co-lactic acid) (10). It was found from the results of hydrolysis of poly(a-malic acid) that the main-chain ester bonds were cleaved randomly and slowly in vitro.

Monodisperse stereocomplex nanogels were obtained through the self-assembly of an equimolar mixture of dextran-graft-poly(L-lactide) (Dex-g-PLLA) and dextran-graft-poly(D-lactide) (Dex-g-PDLA) amphiphilic copolymers with well-defined composition in a dilute aqueous solution. The stereocomplex nanogel possessed partially crystallized cores of hydrophobic polylactide (PLA) and the hydrophilic dextran skeleton by intra- and/or intermolecular self-assembly between PLLA and PDLA chains. The stereocomplex nanogels exhibited significantly lower critical aggregation concentration (CAC) value as well as stronger thermodynamic stability compared with those of the corresponding L- or D-isomer nanogels. The mean diameter of the stereocomplex nanogels was 70 nm with narrow size distribution, implying they were well-defined and presumably nanogels. Furthermore, stereocomplex nanogel exhibited strong kinetic stability. The tunable degradation properties of Dex-g-PLA nanogels were achieved by varying the number of grafted PLA chains as well as applying stereocomplexation. This study demonstrates the advantage of stereocomplexation in the design of biodegradable nanogels with enhanced stability.

No abstract