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1.
Pharm Dev Technol ; 26(2): 167-180, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33213235

RESUMO

Calcium channel blockers such as diltiazem have recently been investigated for their wound-healing potential. The aims of this study were to fabricate diltiazem-loaded nanofibers for a new wound dressing and investigate their beneficial properties for wound healing. Nanofibers were electrospun using polyvinyl alcohol solution containing 0, 2 or 4% diltiazem. Fibers were characterized in terms of physicochemical properties, drug release and fibroblast viability, and in animal wound healing assays. Compared to other formulations, nanofibers containing 4% diltiazem showed thin fiber size (152.7 nm), high porosity (88.4%), high swelling (110.4%), low water contact angle (29.1°) and little weight loss (17.3%). Drug release from 4%-diltiazem nanofibers showed good fit to a Korsmeyer-Peppas model, suggesting a non-Fickian release mechanism (R 2 = 96%, n = 0.52). In vitro, 4%-diltiazem mats were not cytotoxic and enhanced fibroblast proliferation by 263% after 5 days of treatment compared to control. In vivo, wounds treated with this mat for 14 days showed the smallest size (14.7%) and better histopathologic characteristics compared to other wounds. The 4%-diltiazem mat also demonstrated significant antioxidant activity by reducing tissue MDA and nitrite levels by 63 and 59% compared to normal saline. The findings support the eligibility of this novel wound dressing for additional clinical research.


Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Diltiazem/administração & dosagem , Nanofibras , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Bloqueadores dos Canais de Cálcio/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Diltiazem/farmacologia , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Camundongos , Tamanho da Partícula , Álcool de Polivinil/química , Porosidade
2.
Iran J Basic Med Sci ; 23(12): 1590-1602, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33489034

RESUMO

OBJECTIVES: N-acetylcysteine (NAC) has gained attention recently in dermatology as a unique anti-oxidant. In light of progress in nanotechnological methods, it was hypothesized that loading NAC onto nanofibers would positively affect skin wound healing. The objective of this study was to fabricate NAC-loaded electrospun mats and test their effect on wound healing in vivo and in vitro. MATERIALS AND METHODS: Polyvinyl alcohol (PVA)-based mats loaded with NAC at three concentrations were electrospun and characterized in terms of physicochemical properties and drug release profile. Human fibroblast cells (in vitro) and mouse full-thickness skin wounds (in vivo) were treated with mats for 5 and 14 days, respectively. Wound area, tissue histopathology, fibroblast proliferation and cellular oxidative state were evaluated. RESULTS: Mats containing 5% PVA/NAC showed thinner fibers with suitable physicochemical properties and a sustained drug release profile. PVA/NAC (5%) mats enhanced fibroblast proliferation and attachment in vitro. The mats resulted in significant wound closure with high levels of re-epithelialization and collagen fiber synthesis on day 14 post-surgery in vivo. The mats also reduced granulation tissue and edematous stroma to a higher extent. These findings were accompanied by a significant decrease in tissue lipid peroxidation and higher superoxide dismutase activity, which may explain how NAC improved wound healing. CONCLUSION: We propose an NAC-loaded nanofibrous mat that takes the advantage of a porous nanoscaffold structure to release NAC in a sustained manner. This mat may be a promising candidate for further clinical evaluation.

3.
Environ Res ; 182: 109062, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31883495

RESUMO

Health risk and burden of disease induced by exposure to trihalomethanes (THMs, four compounds) and haloacetic acids (HAAs, 5 compounds) from drinking water through ingestion, dermal absorption, and inhalation routes were assessed based on one-year water quality monitoring in four urban communities (Bandar Deylam, Borazjan, Bushehr, and Choghadak) of Bushehr Province, Iran. The total average concentrations of THMs and HAAs at all the communities level were determined to be 92.9 ± 43.7 and 70.6 ± 26.5 µg/L, respectively. The dominant components of the THMs and HAAs were determined to be tribromomethane (TBM, 41.6%) and monobromoacetic acid (MBAA, 60.8%), respectively. The average contributions of ingestion, dermal absorption, and inhalation routes in exposure to the chlorination by-products (CBPs) were respectively 65.0, 15.4, and 19.6%. The total average non-carcinogenic risk as the hazard index (HI) and incremental lifetime cancer risk (ILCR) of the CBPs at all the communities level were found to be 4.03 × 10-1 and 3.16 × 10-4, respectively. The total attributable deaths, death rate (per 100,000 people), age-weighted disability-adjusted life years (DALYs), and age-weighted DALY rate for all ages both sexes combined at all the communities level were estimated to be 1.0 (uncertainty interval: UI 95% 0.3 to 2.8), 0.27 (0.08-0.75), 30.8 (11.3-100.1), and 8.1 (3.0-26.4), respectively. The average contribution of mortality (years of life lost due to premature mortality: YLLs) in the attributable burden of disease was 94.7% (94.4-95.6). Although in most of cases the average levels of the CBPs were in the permissible range of Iranian standards for drinking water quality, the average values of ILCRs as well as attributable burden of disease were not acceptable (the ILCRs were higher than the boundary limit of 10-5); therefore, implementation of interventions for reducing exposure to CBPs through drinking water especially in Kowsar Dam Water Treatment Plant is strictly recommended.


Assuntos
Água Potável , Trialometanos , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Feminino , Humanos , Irã (Geográfico) , Masculino , Medição de Risco , Trialometanos/toxicidade , Poluentes Químicos da Água/toxicidade
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