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1.
Int J Pharm ; 649: 123637, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38008234

RESUMO

Pancreatic cancer is an aggressive malignancy that remains a major cause of cancer-related deaths. Research for innovative anticancer therapeutic options is thus imperative. In this regard, phytotherapeutics offer great promise as efficient treatment modalities, especially leveraging nanodrug delivery. Herein, we innovatively coloaded the flavonoid genistein (Gen) and frankincense essential oil (FO) within cubosomes, which were then coated with the bioactive ligand hyaluronic acid (HA/Gen-FO-Cub) for active-targeting of pancreatic cancer. The novel HA/Gen-FO-Cub displayed optimum nanosize (198.2 ± 4.5 nm), PDI (0.27 ± 0.01), zeta-potential (-34.7 ± 1.2 mV), Gen entrapment (99.3 ± 0.01 %), and controlled Gen release (43.7 ± 1.2 % after 120 h). HA/Gen-FO-Cub exerted selective anticancer activity on pancreatic cancer cells (PANC-1; 8-fold drop in IC50), cellular uptake and anti-migratory effect compared to Gen solution. HA/Gen-FO-Cub revealed prominent cytocompatibility (100 ± 5.9 % viability of human dermal fibroblast). Moreover, HA/Gen-FO-Cub boosted the in vivo anticancer activity of Gen in an orthotopic cancer model, affording tumor growth suppression (2.5-fold drop) and downregulation of NFκB and VEGF (2.9- and 1.8-fold decrease, respectively), compared to Gen suspension. Antimetastatic efficacy and Bcl-2-downexpression was histologically confirmed. Our findings demonstrate the promising anticancer aptitude of HA/Gen-FO-Cub as an effective phytotherapeutic nanodelivery system for pancreatic cancer therapy.


Assuntos
Franquincenso , Neoplasias Pancreáticas , Humanos , Genisteína/farmacologia , Franquincenso/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Ácido Hialurônico
3.
Pharmaceutics ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34575545

RESUMO

Skin restoration following full-thickness injury poses significant clinical challenges including inflammation and scarring. Medicated scaffolds formulated from natural bioactive polymers present an attractive platform for promoting wound healing. Glibenclamide was formulated in collagen/chitosan composite scaffolds to fulfill this aim. Glibenclamide was forged into nanocrystals with optimized colloidal properties (particle size of 352.2 nm, and polydispersity index of 0.29) using Kolliphor as a stabilizer to allow loading into the hydrophilic polymeric matrix. Scaffolds were prepared by the freeze drying method using different total polymer contents (3-6%) and collagen/chitosan ratios (0.25-2). A total polymer content of 3% at a collagen/chitosan ratio of 2:1 (SCGL3-2) was selected based on the results of in vitro characterization including the swelling index (1095.21), porosity (94.08%), mechanical strength, rate of degradation and in vitro drug release. SCGL3-2 was shown to be hemocompatible based on the results of protein binding, blood clotting and percentage hemolysis assays. In vitro cell culture studies on HSF cells demonstrated the biocompatibility of nanocrystals and SCGL3-2. In vivo studies on a rat model of a full-thickness wound presented rapid closure with enhanced histological and immunohistochemical parameters, revealing the success of the scaffold in reducing inflammation and promoting wound healing without scar formation. Hence, SCGL3-2 could be considered a potential dermal substitute for skin regeneration.

4.
Int J Pharm ; 264(1-2): 1-14, 2003 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-12972331

RESUMO

Mucoadhesive patches containing 10mg miconazole nitrate were evaluated. The patches were prepared with ionic polymers, sodium carboxymethyl cellulose (SCMC) and chitosan, or non-ionic polymers, polyvinyl alcohol (PVA), hydroxyethyl cellulose (HEC) and hydroxypropylmethyl cellulose (HPMC). Convenient bioadhesion, acceptable elasticity, swelling and surface pH were obtained. Patches exhibited sustained release over more than 5h and the addition of polyvinyl pyrrolidone (PVP) generally enhanced the release rate. Optimum release behaviour was shown with patches containing 10% w/v PVA and 5% w/v PVP. Study of the in vivo release from this formulation revealed uniform and effective salivary levels with adequate comfort and compliance during at least 6h. On the contrary, in vivo release of the commercial oral gel product resulted in a burst and transient release of miconazole, which diminished sharply after the first hour of application. Storage of these patches for 6 months did not affect the elastic properties, however, enhanced release rates were observed due to marked changes in the crystal habit of the drug.


Assuntos
Antifúngicos/farmacocinética , Celulose/análogos & derivados , Quitina/análogos & derivados , Miconazol/farmacocinética , Mucosa Bucal/metabolismo , Adesividade , Adjuvantes Farmacêuticos/química , Administração Bucal , Administração Oral , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/química , Carboximetilcelulose Sódica/química , Celulose/química , Química Farmacêutica , Quitina/química , Quitosana , Estudos Cross-Over , Preparações de Ação Retardada , Estabilidade de Medicamentos , Feminino , Humanos , Derivados da Hipromelose , Técnicas In Vitro , Masculino , Metilcelulose/análogos & derivados , Metilcelulose/química , Miconazol/administração & dosagem , Miconazol/química , Pessoa de Meia-Idade , Álcool de Polivinil/química , Fatores de Tempo
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