Enzyme-mediated fabrication of nanocomposite hydrogel microneedles for tunable mechanical strength and controllable transdermal efficiency.
Acta Biomater
; 174: 127-140, 2024 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-38042262
ABSTRACT
Microneedles (MNs) are increasingly used in transdermal drug delivery due to high bioavailability, simple operation, and improved patient compliance. However, further clinical applications are hindered by unsatisfactory mechanical strength and uncontrolled drug release. Herein, an enzyme-mediated approach is reported for the fabrication of nanocomposite hydrogel-based MNs with tunable mechanical strength and controllable transdermal efficiency. As a proof-of-concept, tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP) was chosen as a model drug for photodynamic therapy of melanoma. TMPyP-loaded PLGA nanoparticles (NP/TMPyP) served as an inner phase of MNs for controlled release of photosensitizers, and enzyme-mediated hyaluronic acid-tyramine (HAT) hydrogels served as an external phase for optimizing the mechanical strength of MNs. By changing the concentration of HRP and H2O2, three types of MNs were fabricated for transdermal delivery of TMPyP, which demonstrated different cross-linking densities and various mechanical strength. Among the three MNs, the HAT-Medium@NP/TMPyP-MN with a medium mechanical strength exhibited the highest values of transdermal efficiency in vitro and the longest retention time in vivo. As compared to pure TMPyP and TMPyP-loaded nanoparticles, the HAT-Medium@NP/TMPyP-MN demonstrated higher anticancer efficacy in both melanoma A375 cells and a xenografted tumor mouse model. Therefore, the enzyme-mediated nanocomposite hydrogel MNs show great promise in the transdermal delivery of therapeutic drugs with enhanced performance. STATEMENT OF SIGNIFICANCE:
This study reports an enzyme-mediated approach for the fabrication of photodynamically-active microneedles (HAT@NP/TMPyP-MNs) with tunable mechanical strength and controllable transdermal efficiency. On one hand, HAT hydrogels that bear different cross-linking densities, facilitate tunable mechanical strength and optimized transdermal performances of MNs; on the other hand, NP/TMPyP and HAT network contribute to sustained release of photosensitizers. Comparing to other formulation (i.e., NP/TMPyP or TMPyP), the HAT-Medium@NP/TMPyP-MN exhibited excelling anticancer efficacy in photodynamic therapy in vitro and in vivo. We believe that the combination of enzyme-mediated polymeric cross-linking and slow-releasing nano-vehicles in a single nanocomposite platform provides a versatile approach for the fabrication of MNs with enhanced therapeutic efficacy, which holds great promise in the transdermal delivery of various therapeutic drugs in future.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fármacos Fotossensibilizantes
/
Melanoma
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article