RESUMEN

Drug repurposing is a potential strategy to overcome the huge economic expenses of wound healing products. This work aims to develop a topical gel of piroxicam encapsulated into a nanospanlastics vesicular system as an effective, dermal wound dressing. Firstly, piroxicam was entrapped into nanospanlastics formulations and optimized utilizing 23 full factorial experimental designs. The scrutinized factors were Span 60: Edge activator ratio, edge activator type, and permeation enhancer type. The measured responses were vesicle size (VS), polydispersity index (PDI), and% entrapment efficiency (EE). The optimized formula was further adopted into an alginate-pectin gel matrix to maximize adherence to the skin. The rheology and in-vitro release were studied for the developed nanospanlastics gel. Cytotoxicity and wound healing potential using scratch assay were assessed on human adult dermal fibroblast cells. The optimal piroxicam nanospanlastics formula demonstrated a VS of 124.1 ± 1.3 nm, PDI of 0.21 ± 0.01, and EE% of 97.27±0.21%. About 70.0 ± 0.9% and 57.4 ± 0.1% of piroxicam were released from nanospanlastics dispersion and gel within 24 h, respectively. Nanospanlastics gel of piroxicam flowed in a non-Newtonian pseudoplastic shear thinning pattern. It was also biocompatible with the human dermal fibroblast cells and significantly promoted their migration rate which suggests an auspicious cutaneous wound healing aptitude.

Asunto(s)

Reposicionamiento de Medicamentos , Piroxicam , Cicatrización de Heridas , Piroxicam/administración & dosificación , Piroxicam/química , Piroxicam/farmacología , Cicatrización de Heridas/efectos de los fármacos , Humanos , Reposicionamiento de Medicamentos/métodos , Piel/efectos de los fármacos , Piel/metabolismo , Fibroblastos/efectos de los fármacos , Nanopartículas/química , Geles/química , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Administración Cutánea , Vendajes , Liberación de Fármacos , Alginatos/química

RESUMEN

Up to date, there were no approved drugs against coronavirus (COVID-19) disease that dangerously affects global health and the economy. Repurposing the existing drugs would be a promising approach for COVID-19 management. The antidepressant drugs, selective serotonin reuptake inhibitors (SSRIs) class, have antiviral, anti-inflammatory, and anticoagulant effects, which makes them auspicious drugs for COVID 19 treatment. Therefore, this study aimed to predict the possible therapeutic activity of SSRIs against COVID-19. Firstly, molecular docking studies were performed to hypothesize the possible interaction of SSRIs to the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-COV-2) main protease. Secondly, the candidate drug was loaded in lipid polymer hybrid (LPH) nanoparticles to enhance its activity. The studied SSRIs were Fluoxetine hydrochloride (FH), Atomoxteine, Paroxetine, Nisoxteine, Repoxteine RR, and Repoxteine SS. Interestingly, FH could effectively bind with SARS-COV-2 main protease via hydrogen bond formation with low binding energy (-6.7 kcal/mol). Moreover, the optimization of FH-LPH formulation achieved 65.1 ± 2.7% encapsulation efficiency, 10.3 ± 0.4% loading efficiency, 98.5 ± 3.5 nm particle size, and -10.5 ± 0.45 mV zeta potential. Additionally, it improved cellular internalization in a time-dependent manner with good biocompatibility on Human lung fibroblast (CCD-19Lu) cells. Therefore, the study suggested the potential activity of FH-LPH nanoparticles against the COVID-19 pandemic.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , Nanopartículas , Reposicionamiento de Medicamentos , Fluoxetina , Humanos , Lípidos , Simulación del Acoplamiento Molecular , Pandemias , Polímeros , SARS-CoV-2

RESUMEN

The aim of this study was to investigate the feasibility of hexosomes (HEXs) as competent platforms for fluoxetine hydrochloride (FH) repurposing against HepG2 hepatocellular carcinoma. Different FH-loaded HEX formulations were prepared and optimized by the hot emulsification method. The HEX features such as particle size, ζ potential, and drug entrapment efficiency (EE%) can be tailored by tuning HEX components and fabrication conditions. The composition of the optimized FH hexosome (OFH-HEX) was composed of 3.1, 1.4, 0.5, 0.2, and 94.8% for glyceryl monooleate, oleic acid, pluronic F127, FH, and deionized water, respectively. The anionic OFH-HEX with a particle size of 145.5 ± 2.5 nm and drug EE% of 45.4 ± 1.2% was able to prolong the in vitro FH release, where only 19.5 ± 2.3% released in phosphate-buffered saline (PBS) pH 7.4 after 24 h. Contrarily, HEX rapidly released FH in acetate buffer pH 5.5 and achieved a 90.5 ± 4.7% release after 24 h. The obtained HEX showed an improved cellular internalization in a time-dependent manner and enhanced the cytotoxicity (2-fold higher than FH solution). The current study suggests the potential of FH-HEX as a possible anticancer agent against hepatocellular carcinoma.