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1.
Adv Mater ; 34(51): e2207832, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36189863

RESUMO

Dissolving microneedle (DMN) patches are emerging as a minimally invasive and efficient transdermal drug delivery platform. Generally, noncrystalline, water-soluble, and high-molecular-weight polymers are employed in DMNs because their sufficient intermolecular interactions can endow the DMNs with necessary mechanical strength and toughness. However, high viscosity and heavy chain entanglement of polymer solutions greatly hinder processing and dissolution of polymeric DMNs. Here, a strong and tough supramolecular DMN patch made of highly water-soluble cyclodextrin (CD) derivatives is described. Due to the synergy of multiple supramolecular interactions, the CD DMN patch exhibits robust mechanical strength outperforming the state-of-the-art polymeric DMNs. The CD DMN displays ultrafast dissolution (<30 s) in skin models by virtue of the dynamic and weak noncovalent bonds, which also enables the CD DMN and its payloads to diffuse rapidly into the deep skin layer. Moreover, the unique supramolecular structure of CD allows the CD DMNs to load not only hydrophilic drugs (e.g., rhodamine B as a model) but also hydrophobic model drugs (e.g., ibuprofen). As a proof-of-concept, CD DMNs loading ibuprofen show a rapid onset of therapeutic action in a xylene-induced acute inflammation model in mice. This work opens a new avenue for the development of mechanically robust supramolecular DMNs and broadens the applications of supramolecular materials.


Assuntos
Sistemas de Liberação de Medicamentos , Ibuprofeno , Camundongos , Animais , Solubilidade , Pele , Administração Cutânea , Polímeros/química , Microinjeções
2.
J Mater Chem B ; 8(5): 928-934, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912081

RESUMO

Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 µm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion ex vivo. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.


Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização Patológica/tratamento farmacológico , Polímeros/farmacologia , Sirolimo/farmacologia , Malformações Vasculares/tratamento farmacológico , Administração Cutânea , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sistemas de Liberação de Medicamentos , Humanos , Teste de Materiais , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Tamanho da Partícula , Polímeros/administração & dosagem , Polímeros/química , Sirolimo/administração & dosagem , Sirolimo/química , Solubilidade , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Malformações Vasculares/metabolismo , Malformações Vasculares/patologia , Água/química
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