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1.
Biomater Sci ; 11(3): 813-821, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36408890

RESUMO

Electrospun nanofibers are a 3D scaffold of choice for many drug delivery devices due to their high surface area, significant capacity for drug payload, ease of in situ placement, and scalable manufacture. Herein, we report the synthesis of polymeric, pH-responsive nanofiber buttresses via electrospinning. The homopolymer is comprised of an acrylic backbone with acid-sensitive, hydrolyzable, trimethoxybenzaldehyde-protected side chains that lead to buttress transformation from a hydrophobic to a hydrophilic state under physiologically relevant pH conditions (e.g., extracellular tumor environment with pH = 6.5). Hydrolysis of the side chains leads to an increase in fiber diameter from approximately 350 to 900 nm and the release of the encapsulated drug cargo. In vitro drug release profiles demonstrate that significantly more drug is released at pH 5.5 compared to pH 7.4, thereby limiting the release to the target site, with docetaxel releasing over 20 days and doxorubicin over 7 days. Drug burst release, defined as >50% within 24 hours, does not occur at either pH or with either drug. Drug-loaded buttresses preserve drug activity and are cytotoxic to multiple human cancer lines, including breast and lung. Important to their potential application in surgical applications, the tensile strength of the buttresses is 6.3 kPa and, though weaker than commercially available buttresses, they provide sufficient flexibility and mechanical integrity to serve as buttressing materials via the application with a conventional surgical cutting stapler.


Assuntos
Nanofibras , Neoplasias , Humanos , Nanofibras/química , Sistemas de Liberação de Medicamentos , Polímeros/química , Doxorrubicina/farmacologia , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos
2.
Biomacromolecules ; 23(9): 3525-3534, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35696518

RESUMO

Fast-forming yet easily dissolvable hydrogels (HGs) have potential applications in wound healing, burn incidences, and delivery of therapeutic agents. Herein, a combination of a thiol-maleimide conjugation and thiol-disulfide exchange reaction is employed to fabricate fast-forming HGs which rapidly dissolve upon exposure to dithiothreitol (DTT), a nontoxic thiol-containing hydrophilic molecule. In particular, maleimide disulfide-terminated telechelic linear poly(ethylene glycol) (PEG) polymer and PEG-based tetrathiol macromonomers are employed as gel precursors, which upon mixing yield HGs within a minute. The selectivity of the thiol-maleimide conjugation in the presence of a disulfide linkage was established through 1H NMR spectroscopy and Ellman's test. Rapid degradation of HGs in the presence of thiol-containing solution was evident from the reduction in storage modulus. HGs encapsulated with fluorescent dye-labeled dextran polymers and bovine serum albumin were fabricated, and their cargo release was investigated under passive and active conditions upon exposure to DTT. One can envision that the rapid gelation and fast on-demand dissolution under relatively benign conditions would make these polymeric materials attractive for a range of biomedical applications.


Assuntos
Hidrogéis , Compostos de Sulfidrila , Dissulfetos/química , Ditiotreitol , Hidrogéis/química , Maleimidas/química , Oxirredução , Polietilenoglicóis/química , Polímeros/química , Compostos de Sulfidrila/química
3.
Bioconjug Chem ; 33(5): 839-847, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35446015

RESUMO

In recent years, stimuli-responsive degradation has emerged as a desirable design criterion for functional hydrogels to tune the release of encapsulated payload as well as ensure degradation of the gel upon completion of its function. Herein, redox-responsive hydrogels with a well-defined network structure were obtained using a highly efficient thiol-disulfide exchange reaction. In particular, gelation occurred upon combining thiol-terminated tetra-arm polyethylene glycol (PEG) polymers with linear telechelic PEG-based polymers containing pyridyl disulfide units at their chain ends. Rapid gelation proceeds with good conversions (>85%) to yield macroporous hydrogels possessing high water uptake. Furthermore, due to the presence of the disulfide linkages, the thus-obtained hydrogels can self-heal. The obtained hydrogels undergo complete degradation when exposed to environments rich in thiol-containing agents such as dithiothreitol (DTT) and L-glutathione (GSH). Also, the release profile of encapsulated protein, namely, bovine serum albumin, can be tuned by varying the molecular weight of the polymeric precursors. Additionally, it was demonstrated that complete dissolution of the hydrogel to rapidly release the encapsulated protein occurs upon treating these hydrogels with DTT. Cytotoxicity evaluation of the hydrogels and their degradation products indicated the benign nature of these hydrogels. Additionally, the cytocompatible nature of these materials was also evident from a live/dead cell viability assay. One can envision that the facile fabrication and their ability to degrade on-demand and release their payload will make these benign polymeric scaffolds attractive for various biomedical applications.


Assuntos
Hidrogéis , Polietilenoglicóis , Dissulfetos/química , Ditiotreitol , Hidrogéis/química , Oxirredução , Polietilenoglicóis/química , Compostos de Sulfidrila/química
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