The effect of morphology on the drug release in blends, as well as copolymers of LLA and DXO, was investigated by Albertsson and coworkers. The microspheres obtained from blends were more compact and crystalline, while the copolymer microspheres had an amorphous structure that affected the hydrolysis under humid conditions. The storage stability of copolymers was studied for five months and was found to be less than that of blends due to their more crystalline and dense morphology [294]. Albertsson and coworkers [295] reported in another study a nondestructive preparation of resorbable polymer scaffolds with heparin and an osteo‐inductive growth factor covalently bonded to the PLA surface. This was achieved by photochemical vapor‐phase grafting of acrylamide and subsequent reduction of amide groups of polyacrylamide to amino groups for covalently linking heparin and immobilization of osteo‐inductive growth factor, recombinant human bone morphogenetic protein‐2, in the heparin layer.
A functionalized triblock copolymer PLA‐PEG‐PLA with polybasic carboxylic end groups revealed a high drug encapsulation efficiency due to favorable specific interactions between the polymer and loaded drug [296]. A redox‐responsive behavior in copolymers of LLA and 3‐methyl‐6‐(tritylthiomethyl)‐1,4‐dioxane‐2,5‐dione was achieved by postmodification of pendant thiol to disulfide group to assist glutathione‐mediated release of hydrophobic molecules entrapped in polymer nanospheres [139]. The morphology and polymer architecture of polymers affects nanoscale vesicular structure, which shows a significant effect on release of entrapped species. The release rates of 5‐FU and paclitaxel, widely used chemotherapeutics, were investigated in di‐, tri‐, and four‐arm (star‐branched) block copolymers of LA and EO. Micellar aggregates were prepared from these block copolymers and release rates were studied over three weeks. More complete drug release was observed in star‐shaped polymers [192].
A nanoparticle carrier based on PLGA demonstrated both high biocompatibility and low toxicity and which was found to improve the efficacy of the drug with reduced side effects against lung cancer [297]. A copolymer of LA and CL alone or with renewable polymers such as chitosan as an electrospun membrane applications matrix shows application in tissue regeneration and drug delivery [298, 299]. The synergistic affect in properties is provided by utility of both synthetic and chitosan polymer. Penta‐block copolymer, PLA‐PCL‐PEG‐PCL‐PLA, in the form of spherical micelles/nanovehicles are good for ocular drug permeability and drug delivery due to combination of hydrophobic/hydrophilic blocks with appreciable biocompatibility [300, 301].
A star‐shaped cholic acid‐core poly(CL‐ran‐LA)‐b‐PEG copolymer act as a promising drug‐loaded biomaterial for liver cancer chemotherapy [302]. Further the protein fouling by enzymes was lowered by block copolymer nanoparticles through self‐assembly of PEO‐b‐PLA [303]. Modified thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption for chemotherapy of lung cancer [304]. Linear and star‐shaped amphiphilic PEG‐b‐PLA with or without β‐cyclodextrin (β‐CD) conjugation were synthesized. Oil‐based formulations are formed by emulsion method in organic solvent with a defined core‐shell structure and a particle size of ~150–300 nm. Such reverse micelles (RMs), consisting of a hydrophilic core surrounded by hydrophobic surface, were constructed using PEG‐b‐PLA‐β‐CD in nonpolar solvents and used to sequester hydrophilic guest molecules. They have attracted much attention as drug delivery cargos, as they can form a continuum with other lipid barriers in the body, such as skin lipids and cell membranes. This oil‐based formulation fabricated from above‐mentioned copolymer allowed a high percentage of protein loading, which is prudential for cellular delivery [305].
4.6.2 Radiation Effects
The effect of radiation (γ‐ and electron‐beam) on the degradation of PLA and its copolymers received considerable attention in the past [274, 306, 307]. Irradiation of polymers generates free radicals that induce chemical changes such as chain scission and cross‐linking. The atmosphere of the surroundings, irradiation dose, chemical composition, and morphology of the polymer influence the degradation mechanism. The type of end groups, pendant units, and copolymer structure (such as aromatic or aliphatic units) showed a significant effect on the stability of the polymers toward irradiation. In aliphatic polyesters, the ester linkage and the tertiary carbons in the branched polyesters are the preferred site for the degradation. Mechanical properties and molar mass are significantly affected by radiation. Therefore, the sterilization method should be carefully chosen. Ethylene oxide is mainly used when sterilizing degradable devices, by tuning the method can implants be sterilized without influencing the polymer. Electron beams and γ‐rays are also used for the sterilization of implants [306]. Generally, a dose of 25 kGy is used for such purposes [308]. Albertsson and coworkers [309] reported that copolymerization of LLA with a small amount of CL or DXO increased the stability in comparison to PLLA. The most abundant low molar mass degradation product was identified as DXO.
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