Читать книгу Poly(lactic acid) - Группа авторов - Страница 104

The successful utilization of polymer materials within the living body is highly dependent on the structural architecture and monomer unit distribution in the polymer. Nanoparticles with a hydrophobic surface (e.g., PLA and PLGA) are rapidly taken up by the cells of the reticuloendothelial systems (RES) [292]. Polymer particles with a hydrophilic surface can avoid this uptake to a greater extent, thereby prolonging the lifetime in the blood circulation, which may help in efficient delivery of the therapeutic agent. Self‐organizing block copolymers offers the possibility of entrapping a hydrophobic drug in the micelle core while the micelle’s hydrophilic shell confers water solubility. Intelligent drug delivery vehicles can be designed by utilizing shell forming polymers that exhibit stimuli‐responsive behavior. Block copolymers of DLA and NIPAAm are widely investigated as potentially useful carriers for targeted delivery [41,72–74]. Particles prepared from an amphiphilic polymer usually possess tendency to self‐organize besides providing functional sites where chemical modifications can be easily carried out. Such modifications may provide opportunities for altering specific surface characteristics such as charge, hydrophilicity, and targeting capabilities. Degradable graft copolymers with amino acids [lysine (Lys), aspartic acid (Asp), alanine (Ala), etc.] as polyester–polyamino acid hybrids have been prepared where the side chains can be at neutral pH poly(LA‐co‐Ala), positively charged poly(LAco‐Lys), or negatively charged (poly(LA‐co‐Asp). In such copolymers, the amine side chains tend to concentrate at the surface of the particles [293]. The capabilities of microparticles to serve as carriers in controlled drug release and delivery devices were demonstrated by encapsulation and release of rhodamine B, a low molar mass model.

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].