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ACS Appl Bio Mater ; 7(6): 4051-4061, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38790078

RESUMO

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.


Assuntos
Administração Cutânea , Atorvastatina , Hiperlipidemias , Micelas , Agulhas , Hiperlipidemias/tratamento farmacológico , Animais , Atorvastatina/química , Atorvastatina/administração & dosagem , Atorvastatina/farmacologia , Ratos , Tamanho da Partícula , Materiais Biocompatíveis/química , Polímeros/química , Teste de Materiais , Ratos Sprague-Dawley , Sistemas de Liberação de Medicamentos , Masculino
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