Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment.

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson's disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

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Purpose We created and evaluated an enhanced topical delivery system featuring a combination of highly skin-permeable growth factors (GFs), quercetin (QCN), and oxygen; these synergistically accelerated re-epithelialization and granulation tissue formation of/in diabetic wounds by increasing the levels of GFs and antioxidants, and the oxygen partial pressure, at the wound site. Methods To enhance the therapeutic effects of exogenous administration of GFs for the treatment of diabetic wounds, we prepared highly skin-permeable GF complexes comprised of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF), genetically attached, via the N-termini, to a low-molecular-weight protamine (LMWP) to form LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and LMWP-bFGF, respectively. Furthermore, quercetin (QCN)- and oxygen-carrying 1-bromoperfluorooctane (PFOB)-loaded nanoemulsions (QCN-NE and OXY-PFOB-NE) were developed to improve the topical delivery of QCN and oxygen, respectively. After confirming the enhanced penetration of LMWP-GFs, QCN-NE, and oxygen delivered from OXY-PFOB-NE across human epidermis, we evaluated the effects of combining LMWP-GFs, QCN-NE, and OXY-PFOB-NE on proliferation of keratinocytes and fibroblasts, and the chronic wound closure rate of a diabetic mouse model. Results The optimal ratios of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, LMWP-bFGF, QCN-NE, and OXY-PFOB-NE were 1, 1, 0.02, 0.02, 0.2, and 60, respectively. Moreover, a Carbopol hydrogel containing LMWP-GFs, QCN-NE, and OXY-PFOB-NE (LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL) significantly improved scratch-wound recovery of keratinocytes and fibroblasts in vitro compared to that afforded by hydrogels containing each component alone. LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL significantly accelerated wound-healing in a diabetic mouse model, decreasing wound size by 54 and 35% compared to the vehicle and LMWP-GFs, respectively. Conclusion LMWP-GFs/QCN-NE/OXY-PFOB-NE-GEL synergistically accelerated the healing of chronic wounds, exerting both rapid and prolonged effects.

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ObjectiveThe current study sought to design an oral delivery system of pemetrexed (PMX), a multitargeted antifolate antimetabolite, by enhancing its intestinal membrane permeability.Materials and methodsPMX was ionically complexed with a permeation enhancer such as Nα-deoxycholyl-l-lysyl-methylester (DCK) and prepared as an amorphous solid dispersion by mixing with dispersants such as 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and poloxamer 188 (P188), forming an HP-beta-CD/PMX/DCK/P188; the complex was incorporated into multiple water-in-oil-in-water nanoemulsions in a supersaturated state (HP-beta-CD/PMX/DCK/P188-NE).ResultsAfter complex formation, the partition coefficient and in vitro membrane permeability of PMX were markedly increased, but it showed similar cytotoxic and inhibitory effects on cancer cell proliferation/migration. Furthermore, the intestinal membrane permeability and epithelial cell uptake of PMX were synergistically improved after HP-beta-CD/PMX/DCK/P188 was incorporated into a nanoemulsion with a size of 14.5±0.45 nm. The in vitro permeability of HP-beta-CD/PMX/DCK/P188-NE across a Caco-2 cell monolayer was 9.82-fold greater than that of free PMX, which might be attributable to the partitioning of PMX to the epithelial cells being facilitated via specific interaction of DCK with bile acid transporters, as well as the enhanced lipophilicity accompanied by surfactant-induced changes in the intestinal membrane structure and fluidity. Therefore, the oral bioavailability of HP-beta-CD/PMX/DCK/P188-NE in rats was evaluated as 26.8%±2.98% which was 223% higher than that of oral PMX. Moreover, oral HP-beta-CD/PMX/DCK/P188-NE significantly suppressed tumor growth in Lewis lung carcinoma cell-bearing mice, and the tumor volume was maximally inhibited by 61% compared with that in the control group.ConclusionThese results imply that HP-beta-CD/PMX/DCK/P188-NE is an effective and promising delivery system for enhancing the oral absorption of PMX. Thus, there is the potential for new medical applications, including applications in metronomic cancer treatment.

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