A series of host-guest interaction-adjusted polylactide stereocomplex micelles was prepared via the self-assembly of 4-armed poly(ethylene glycol)-block-poly(L-lactide/D-lactide)-cholesterol(4-armed PEG-b-PLLA/PDLA-CHOL) and poly(β-cyclodextrin)(PCD) with the molar ratios of CHOL/β-CD at 1:0.5, 1:1, and 1:2 in an aqueous environment. The hydrodynamic diameters of the micelles ranged from 84.1 nm to 107 nm depending on the molar ratio of CHOL/β-CD. It was shown that the micelle with the largest proportion of PCD possessed excellent abilities in drug release, cell internalization as well as proliferation inhibitory effect toward human A549 lung cancer cells. The results demonstrated that the stereocomplex and host-guest interactions-mediated PLA micelles exhibited great potential in sustained drug delivery.
Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide)(PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst. The amphiphilic copolymer self-assembled into micelles in aqueous solutions, and formed hydrogels as the increase of temperature at relatively high concentrations(> 15 wt%). The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments. The good cellular and tissular compatibilities of the thermogel were demonstrated. The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEGPLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.
A series of well-defined amphiphilic linear-dendritic block copolymers(telodendrimers, MPEG-b-PAMAM-cholesterol) with 1,2,4 or 8 cholesteryl groups(named as P1, P2, P4, P8, respectively) were synthesized. Their chemical structures were characterized with 1H NMR and mass spectrum(MALDI-TOF MS). The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin(DOX) and paclitaxel(PTX) for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is increased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counterparts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles(NPs) of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements(DLS) and transmission electron microscope(TEM). In vitro drug release experiment demonstrated that P8 exhibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxicity experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug(DOX or PTX). This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.
Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly(L-lactide)(PLA) and poly(ε-caprolactone)(PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media(i.e., phosphate-buffered saline) maintained at a constant p H of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson's trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.
