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The epoch of nanotechnology has authorized novel investigation strategies in the area of drug delivery. Liposomes are attractive biomimetic nanocarriers characterized by their biocompatibility, high loading capacity, and their ability to reduce encapsulated drug toxicity. Nevertheless, various limitations including physical instability, lack of site specificity, and low targeting abilities have impeded the use of solo liposomes. Metal nanocarriers are emerging moieties that can enhance the therapeutic activity of many drugs with improved release and targeted potential, yet numerous barriers, such as colloidal instability, cellular toxicity, and poor cellular uptake, restrain their applicability in vivo. The empire of nanohybrid systems has shelled to overcome these curbs and to combine the criteria of liposomes and metal nanocarriers for successful theranostic delivery. Metallic moieties can be embedded or functionalized on the liposomal systems. The current review sheds light on different liposomal-metal nanohybrid systems that were designed as cellular bearers for therapeutic agents, delivering them to their targeted terminus to combat one of the most widely recognized diseases, cancer.
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INTRODUCTION: Triple negative breast cancer is an aggressive disorder which accounts for at least 15% of breast cancer diagnosis and a high percentage of breast cancer morbidity, hence intensive research efforts are focused on the development of effective therapies to overcome the disease. Thymoquinone (TQ), the bioactive constituent of Nigella sativa, exhibits anticancer activity, yet its translation to the clinic is hindered by its poor bioavailability and lack of quantification method in blood and tissues. To overcome these limitations, cubosomes were utilized for the encapsulation and delivery of this anticancer molecule. METHODS: Thymoquinone loaded cubosomes were prepared through the emulsification homogenization method. The physicochemical characteristics, including particle size, zeta potential, morphology and entrapment efficiency, were studied. Moreover, the in vitro antitumor activity was tested on breast cancer cell lines (MCF-7 and MDA-MB-231) and compared to non-tumorigenic cell line (MCF-10A). Subcellular localization, cellular uptake and apoptotic effects of the formulations were assessed. RESULTS: The results revealed that the TQ loaded cubosomal formulation exhibited a mean particle size of 98.0 ± 4.10 nm with narrow unimodal distribution. The high entrapment efficiency (96.60 ± 3.58%) and zeta potential (31.50 ±4.20 mV) conceived the effectiveness of this nanosystem for TQ encapsulation. Cell viability in both breast cancer cell lines demonstrated a dose-dependent decrease in response to treatment with free TQ or TQ-loaded cubosomes, with enhanced antitumor activity upon treating with the latter formulation. A significant increase in apoptotic bodies and cleaved caspase 3 was observed upon treatment of MDA-MB-231 cells with either TQ or TQ-loaded cubosomes. Localization and trafficking studies unveiled that cubosomes accumulate in the cytoplasm of the studied breast cancer cell lines. DISCUSSION: Our results show that thymoquinone encapsulation in cubosomal nanoparticles provides a promising anticancer drug delivery system with the ability to label, detect and subsequently trace it within the human cells.
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Antineoplásicos Fitogénicos/farmacología , Benzoquinonas/farmacología , Nanopartículas/química , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Benzoquinonas/administración & dosificación , Benzoquinonas/química , Benzoquinonas/farmacocinética , Neoplasias de la Mama/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Células MCF-7 , Nanopartículas/administración & dosificación , Tamaño de la PartículaRESUMEN
The topical delivery of nanotherapeutics at the injury site for skin regeneration has received increasing attention as a strategy for wound treatment. This study aimed to investigate the preparation of spray dried tadalafil loaded pro-nanoliposomes powder as a novel system to accelerate wound healing process. The optimization was carried out employing 32 factorial design based on phospholipid and cholesterol concentrations. The physicochemical characterizations, in vitro cellular assessment and in vivo performance were evaluated. The results obtained pointed out that phospholipid concentration presented a positive effect on the entrapment efficacy and particle size, while cholesterol hindered the entrapment efficacy yet presented a prominent influence on particle size. Moreover, the optimized formulation showed a sustained release, high zeta potential and uniform spherical particles indicating entrapment of tadalafil in its amorphous state as demonstrated by FTIR and XPRD results. Cell viability and in vitro scratch assay demonstrated no cytotoxicity on human fibroblast cell lines and the ability of the drug and optimized formulation to promote cell migration. In vivo wound healing studies revealed significantly higher wound closure rates for areas treated with optimized loaded-formulation (65.95±6.47%) compared to unloaded formulation (29.78±9.65%), free drug (38.87±11.44%) and sham group (10.22±5.11%). In the in vivo study, histopathological specimens supported the previous results with presentation of cascade of healing elements via the angiogenetic activity of tadalafil. These outcomes provide an insight of a novel and emerging therapeutic drug system for wound treatment in clinical practice.
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Portadores de Fármacos , Cicatrización de Heridas , Humanos , Tamaño de la Partícula , Polvos , TadalafiloRESUMEN
The limited solubility of BCS class II drugs diminishes their dissolution and thus reduces their bioavailability. Our aim in this study was to develop and optimize a spray dried emulsion containing indomethacin as a model for Class II drugs, Labrasol®/Transuctol® mixture as the oily phase, and maltodextrin as a solid carrier. The optimization was carried out using a 2(3) full factorial design based on two independent variables, the percentage of carrier and concentration of Poloxamer® 188. The effect of the studied parameters on the spray dried yield, loading efficiency and in vitro release were thoroughly investigated. Furthermore, physicochemical characterization of the optimized formulation was performed. In vivo bioavailability, ulcerogenic capability and histopathological features were assessed. The results obtained pointed out that poloxamer 188 concentration in the formulation was the predominant factor affecting the dissolution release, whereas the drug loading was driven by the carrier concentration added. Moreover, the yield demonstrated a drawback by increasing both independent variables studied. The optimized formulation presented a complete release within two minutes thus suggesting an immediate release pattern as well, the formulation revealed to be uniform spherical particles with an average size of 7.5µm entrapping the drug in its molecular state as demonstrated by the DSC and FTIR studies. The in vivo evaluation, demonstrated a 10-fold enhancement in bioavailability of the optimized formulation, with absence of ulcerogenic side effect compared to the marketed product. The results provided an evidence for the significance of spray dried emulsion as a leading strategy for improving the solubility and enhancing the bioavailability of class II drugs.