PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering

By mimicking the native extracellular matrix, electrospun nanofibrous scaffolds (ENSs) can provide both chemical and physical cues to modulate cell adherence and differentiation and to promote tissue regeneration while retaining bioresorbable and biocompatible properties. In this study, ENSs were developed to deliver multiple biomolecules by loading them into the core-sheath structure and/or by conjugating them to the nanofiber surfaces. In this work, poly(L-lactide)-poly(ethylene glycol)-NH2 and poly(L-lactide) were emulsion electrospun into nanofibers with a core-sheath structure. A model drug, tetracycline hydrochloride, was loaded within the nanofibers. Amino and carboxyl reactive groups were then activated on the fiber surfaces using saturated water vapor exposure and base hydrolysis, respectively. These reactive groups allowed the surface of the ENS to be functionalized with two other bioactive molecules, fluorescein isothiocyanate- and rhodamine-labeled bovine serum albumins, which were used as model proteins. The ENSs were shown to retain their antimicrobial capacity after two functionalization reactions, indicating that multifunctional nanofibers can potentially be developed into functional wound dressings or periodontal membranes or used in more complicated tissue systems where multiple growth factors and anti-infection precautions are critical for the successful implantation and regeneration of tissues

Photo-cross-linked and pH-Sensitive Biodegradable Micelles for Doxorubicin Delivery

Cross-linked polymeric micelles have gained increasing research interest in the past decade due to the instability of existing polymeric micelles when used in vivo. In this study, we reported a series of covalently cross-linked pH-sensitive biodegradable micelles based on the poly­(ethylene glycol)-hyperbranched poly­(β-aminoester)­s with acrylate group terminals (PEG-HBPAE-A) copolymers for intracellular delivery of doxorubicin (DOX). PEG-HBPAE-A can be self-assembled to form micellar nanoparticles in aqueous solution with diameters of approximately 160 nm. The non-cross-linked micelles (NCLMs) were cross-linked upon UV irradiation to form cross-linked micelles (CLMs). ¹H NMR, FT-IR and dynamic light scattering (DLS) were utilized to investigate the process of the UV cross-linking and the stability of CLMs. The results showed the significantly enhanced stability for CLMs in comparison to NCLMs. pH sensitivity of CLMs and NCLMs were also estimated by DLS. In vitro drug release studies confirmed that DOX release from DOX-loaded CLMs was greatly inhibited upon the neutral pH environment, whereas DOX underwent faster release in acidic conditions. MTT assays showed that DOX-loaded micelles had a similar inhibition rate for HepG-2 and MCF-7 cell lines compared with free DOX, whereas the blank CLMs and NCLMs showed very low cytotoxicity. Laser scanning confocal microscopy and real-time in situ fluorescence microscopy were exploited to investigate drug uptake in cells and drug distribution in the interior of cells. These results showed a promising nanocarrier for intracellular DOX delivery with great potential for cancer therapy