Formulation and Characterization of Chitosan-Decorated Multiple Nanoemulsion for Topical Delivery In Vitro and Ex Vivo.

In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the stratum corneum, which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.

Innovative multiple nanoemulsion (W/O/W) based on Chilean honeybee pollen improves their permeability, antioxidant and antibacterial activity.

Beehive derivatives, including honeybee pollen (HBP), have been extensively studied for their beneficial health properties and potential therapeutic use. Its high polyphenol content gives it excellent antioxidant and antibacterial properties. Today its use is limited due to poor organoleptic properties, low solubility, stability, and permeability under physiological conditions. A novel edible multiple W/O/W nanoemulsion (BP-MNE) to encapsulate the HBP extract was designed and optimized to overcome these limitations. The new BP-MNE has a small size (∼100 nm), a zeta potential greater than +30 mV, and efficiently encapsulated phenolic compounds (∼82%). BP-MNE stability was measured under simulated physiological conditions and storage conditions (4 months); in both cases, stability was promoted. The formulation's antioxidant and antibacterial (Streptococcus pyogenes) activity was analyzed, obtaining a higher effect than the non-encapsulated compounds in both cases. In vitro permeability was tested, observing a high permeability of the phenolic compounds when they are nanoencapsulated. With these results, we propose our BP-MNE as an innovative solution to encapsulate complex matrices, such as HBP extract, as a platform to develop functional foods.

A novel 5-Fluorocuracil multiple-nanoemulsion used for the enhancement of oral bioavailability in the treatment of colorectal cancer.

5-Fluorouracil (5-FU) is a drug of choice for colorectal-cancer. But oral therapeutic efficacy of 5-FU is restricted due to their very little bioavailability because of poor membrane permeability and GIT-absorption. We have developed a multiple nanoemulsion (w/o/w i.e. 5-FU-MNE) in which 5-FU incorporated to improve their oral-absorption. Globule-size of opt-5-FU-MNE was 51.64 ±â€¯2.61 nm with PDI and ZP 0.101 ±â€¯0.001 and -5.59 ±â€¯0.94, respectively. In vitro 5-FU-release and ex vivo permeation studies exhibited 99.71% release and 83.64% of 5-FU from opt-nanoformulation. Cytotoxic in vitro studies-exhibited that 5-FU in opt-5-FU-MNE was 5-times more potent than 5-FU-S on human-colon-cancer-cell-lines (HT-29). The enhanced Cmax with AUC0-8h with opt-5-FU-MNE was shown extremely significant (p < 0.001) in wistar rat's plasma in the comparison of oral and i.v. treated group of 5-FU-S by PK-observations. Furthermore, opt-5-FU-MNE was showed much more significant (p < 0.001) results as compared to 5-FU-S (free) on cell lines for human colon cancer (HT-29).

Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin.

Co-administration of conventional and natural chemotherapeutics offers synergistic anticancer efficacy while minimizing adverse effects. In this study, an oral co-delivery system for pemetrexed (PMX) and quercetin (QCN) was designed based on water-in-oil-in-water nanoemulsion (NE), which is highly absorbable because it enhances the intestinal membrane permeability of PMX and aqueous solubility of QCN. To create this system, an ion-pairing complex of PMX with Nα-deoxycholyl-l-lysyl-methylester (DCK) was formed and further incorporated with QCN into the NE, yielding PMX/DCK-QCN-NE. The results revealed synergistic inhibitory effects on human lung carcinoma (A549) cell proliferation and migration after combined treatment with PMX/DCK and QCN. The intestinal membrane permeability and cellular uptake of PMX/DCK and QCN from the NE were significantly improved via facilitated transport of PMX by the interaction of DCK with bile acid transporters, as well as NE formulation-mediated alterations in the membrane structure and fluidity, which resulted in 4.51- and 23.9-fold greater oral bioavailability of PMX and QCN, respectively, than each free drug. Tumor growth in A549 cell-bearing mice was also maximally suppressed by 62.7% after daily oral administration of PMX/DCK-QCN-NE compared with controls. Thus, PMX/DCK-QCN-NE is a promising oral nanocarrier of PMX and QCN for synergistic anticancer efficacy and long-term chemotherapy.

Physicochemical Property and Oxidative Stability of Whey Protein Concentrate Multiple Nanoemulsion Containing Fish Oil.

The objectives of this research were to produce whey protein concentrate (WPC) multiple nanoemulsion (MNE) and to study how whey protein concentration level and antioxidant type affected the physicochemical properties and oxidative stability of fish oil in MNE. The morphological and physicochemical characteristics of MNE were investigated by using transmission electron microscopy and particle size analyzer, respectively. The oxidative stability of fish oil in MNEs was assessed by measuring peroxide value (PV), p-anisidine value, and volatile compounds. The spherical forms of emulsions with size ranging from 190 to 210 nm were observed indicating the successful production of MNE. Compared with free fish oil, fish oil in MNE exhibited lower PV, p-anisidine value, and formation of maker of oxidation of fish oil indicating the oxidative stability of fish oil in MNE was enhanced. PV, p-anisidine value, and makers of oxidation of fish oil were decreased with increased WPC concentration level. The combined use of Vitamin C and E in MNE resulted in a reduction in PV and p-anisidine value, and development of maker of oxidation. In conclusion, WPC concentration level and antioxidant type are key factors affecting the droplet size of MNE and oxidative stability of fish oil.