RESUMO
Nanoemulgel (NEG) pharmaceutical formulations are gaining popularity because of their ability to serve both as a nanoemulsion and as a gel. These products are well-known for their ease of use, spreadability, controlled release, and ability to hydrate dry skin. Natural essential oils have been shown to promote the cutaneous permeability of topical formulations, enhancing medication safety and efficacy. Herein, we developed NEG for the enhanced permeation of ketoconazole against candidiasis using clove oil (clove-oil-NEG) or eucalyptus oil (eucalyptus-oil-NEG), using the gelling agents carbopol 943 and hydroxypropyl methylcellulose (HPMC). We tested various excipients to increase the solubility of ketoconazole and formulate a nanoemulsion (NE). We measured the NE droplet particle size, shape, entrapment efficiency, and drug release. Furthermore, the physicochemical properties of the optimized nanoemulsion formulation were characterized by techniques such as Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. The NEs were loaded into gels to form NEGs. NEGs were characterized for drug content, homogeneity, rheology, spreadability, and antifungal activity against Candida albicans, both in vitro and in vivo. Optimized ketoconazole NEG preparations consisted of either 15% clove oil or 20% eucalyptus oil. Droplet sizes in the optimized NEs were <100 nm, and the polydispersity indexes were 0.24 and 0.26. The percentages of ketoconazole released after 24 h from the clove-oil-NEG and eucalyptus-oil-NEGs were 91 ± 4.5 and 89 ± 7%, respectively. Scanning electron microscopy (SEM) showed that the NEGs had a smooth, uniform, and consistent shape and internal structural organization. The drug contents in the clove-oil-NEG and eucalyptus-oil-NEG were 98.5 ± 2.2 and 98.8 ± 3.4%, respectively. Permeation values of ketoconazole from clove-oil-NEG and eucalyptus-oil-NEG were 117 ± 7 and 108.34 ± 6 µg cm-2, respectively. The ketoconazole NEG formulations also had higher levels of fungal growth inhibition than a marketed formulation. Finally, in vivo studies showed that the NEGs do not irritate the skin. Ketoconazole NEG with either 15% clove oil or 20% eucalyptus oil is stable with better efficacy than ketoconazole alone due to excellent dispersion, drug dissolution, and permeability and thus might be recommended for the effective and safe treatment of candidiasis.
RESUMO
The plain 5-fluorouracil (5FU) formulations available in the market are associated with adverse effects such as skin irritation, pruritus, redness, blisters, allergy, and dryness on the site of application. The objective of the present study was to develop a liposomal emulgel of 5FU with increased skin permeability and efficacy using clove oil and eucalyptus oil along with pharmaceutically acceptable carriers, excipients, stabilizers, binders, and additives. A series of seven formulations were developed and evaluated for their entrapment efficiency, in vitro release profile, and cumulative drug release profile. The compatibility of drugs and excipients, as confirmed by FTIR (fourier-transform infrared spectroscopy) and DSC (differential scanning calorimetry) as well as SEM (scanning electron microscopy) and TEM (transmission electron microscopy) studies, revealed that the size and shape of liposomes are smooth and spherical, and the liposomes are non-aggregated. To understand their efficacy, the optimized formulations were evaluated for cytotoxicity using B16-F10 mouse skin melanoma cells. The eucalyptus oil and clove oil-containing preparation significantly produced a cytotoxic effect against a melanoma cell line. The addition of clove oil and eucalyptus oil increased the efficacy of the formulation by improving skin permeability and reducing the dose required for the anti-skin cancer activity.
RESUMO
The purpose of this study was to prepare and characterize levocetirizine hydrochloride loaded liposome of by film hydration technique followed by sonication. Sorbitol was added to facilitate the hydration of dried liposome into vesicles or to prepare rehydration system. The liposomes were characterized for size, shape, entrapment efficiency, in vitro drug release and stability. The morphology of liposomes was characterized through a phase-contrast microscope and transmission electron microscope. The percent entrapment efficiency and particle size varied between 55.6 ± 0.21 to 81.2 ± 0.52 and 15.73 ± 0.99 to 24.52 ± 0.97 µm, respectively. The drug release increased at higher concentration of phospholipids. On the other hand, the drug release was decreased at higher concentration of cholesterol. The preliminary results of this study suggest that the developed multi-lamellar vesicles containing levocetirizine hydrochloride could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.