RESUMO
Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.
Assuntos
Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Pé Diabético/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Sapogeninas/farmacologia , Elastômeros de Silicone/química , Inibidores da Angiogênese/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Pé Diabético/patologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Géis/administração & dosagem , Géis/química , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Lipídeos/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Nanoestruturas/química , Neovascularização Patológica/patologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Tamanho da Partícula , Células RAW 264.7 , Sapogeninas/administração & dosagem , Sapogeninas/química , Elastômeros de Silicone/administração & dosagem , Propriedades de Superfície , Cicatrização/efeitos dos fármacosRESUMO
Discovery of agents for oral infectious diseases is always encouraged in natural products chemistry. A bioassay-guided isolation led to the isolation of two new acetylenic acids (1, 2) along with seven known ones (3-9) from the ethanol extract of Thesium chinense Turcz, a commonly used oral anti-bacterial and anti-inflammatory herb. Their structures were elucidated on the basis of spectroscopic and chemical evidence. Exocarpic acid (3) demonstrated the most promising activity against three tested oral pathogenic bacterial strains, Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans, with minimum inhibitory concentration values of 0.86, 3.43, and 13.70 µg/mL, respectively. Compounds 1, 2, 4, 5 and 7 also showed potential activities against periodontal bacteria (P. gingivalis, F. nucleatum).