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1.
Int J Mol Sci ; 25(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39337510

RESUMO

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.


Assuntos
Sulfatos de Condroitina , Nanopartículas , Sulfatos de Condroitina/química , Animais , Suínos , Nanopartículas/química , Regeneração/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Administração Tópica , Nanoestruturas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Pele/efeitos dos fármacos , Pele/metabolismo
2.
Int J Pharm ; 554: 105-115, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30395953

RESUMO

Clotrimazole (CLT) was formulated in a nanoemulsion (NE) for the topical treatment of candidiasis consisting of 10% labrafac® lipophile, 60% labrasol®:capryol® 90 mixture (ratio 4:1) and 30% propylene glycol. Physicochemical properties, stability, rheology, in vitro drug release, ex vivo drug permeation through human skin and porcine buccal, sublingual and vaginal mucosae, antifungal efficacy, as well as in vivo skin tolerance were evaluated. 1% CLT-NE (CLT-NE1) and 2% CLT-NE (CLT-NE2) exhibited 153 ±â€¯17.25 and 186 ±â€¯15.38 nm droplet sizes, low polydispersity indexes, negative zeta potentials and biocompatible pH values. The CLT-NEs exhibited typical Newtonian profiles with viscosities of 42.14 ±â€¯0.037 mPa·s and 41.35 ±â€¯0.041 mPa·s, respectively and higher extensibility properties than commercial counterparts retaining their physicochemical properties for 180 days. NEs provided a sustained release of drug according to the first order model. Similar skin permeation properties were observed between CLT-NE1 and commercial reference. However, significant higher CLT amounts retained in mucosae were provided by CLT-NE2 when compared with references. Antifungal efficacies were also higher than commercial references, and the in vivo tolerance study confirmed the suitability for topical application, making CLT-NEs a great tool for clinical investigation of topical candidiasis treatments.


Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Clotrimazol/administração & dosagem , Nanopartículas , Administração Tópica , Adulto , Animais , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Candidíase/microbiologia , Química Farmacêutica/métodos , Clotrimazol/farmacocinética , Clotrimazol/farmacologia , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Emulsões , Excipientes/química , Feminino , Humanos , Concentração de Íons de Hidrogênio , Mucosa/metabolismo , Tamanho da Partícula , Absorção Cutânea , Suínos , Viscosidade
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