Influence of sonophoresis on transdermal drug delivery of hydrophilic compound-loaded lipid nanocarriers.

The effect of sonophoresis on the transdermal drug delivery of sodium fluorescein (NaFI)-loaded lipid nanocarriers such as liposomes (LI), niosomes (NI) and solid lipid nanoparticles (SLN) was investigated by confocal laser scanning microscopy (CLSM), fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that SN decreased the skin penetration of NaFI-loaded SLN (6.32-fold) and NI (1.79-fold), while it increased the penetration of NaFI-loaded LI (5.36-fold). CLSM images showed the red fluorescence of the LI and NI bilayer on the superficial layer of the stratum corneum. However, the red fluorescent probe of the SLN was not visualized in the skin. FTIR results of the LI and NI with SN showed no effect on lipid stratum corneum ordering, suggesting that the fragment of bilayer vesicles might repair the damaged skin. For SLN, the strengthening of stratum corneum by covering the disrupted skin with solid lipids was shown. SEM images show disrupted carriers of all the formulations adsorbed onto the damaged skin. In conclusion, the SN changed the properties of both the skin surface and lipid nanocarrier, demonstrating that disrupted skin might be repaired by a disrupted nanocarrier.

Development, Characterization and Skin Interaction of Capsaicin-Loaded Microemulsion-Based Nonionic Surfactant.

The aim of this study was to develop novel microemulsions (MEs) for the transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants consisting of isopropyl myristate as the oil phase, various nonionic surfactants as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and reverse osmosis water as the aqueous phase were formulated. Based on the optimal ME obtained from Design Expert, MEs containing a fixed concentration of oil, water or surfactant were prepared while varying the amounts of the other two fractions. The results indicated that the skin permeation flux of low dose capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the commercial product and capsaicin in ethanol (control) by approximately two- and four-fold, respectively. We successfully demonstrated the feasibility of the transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic surfactant and ethanol. Moreover, the optimization using computer program helped to simplify the development of a pharmaceutical product.

Fabrication and evaluation of cationic exchange nanofibers for controlled drug delivery systems.

The number of ion exchange fibers in development has increased over the last several years. However, few studies have reported the use ion-exchange fibers in drug delivery system. In this study polystyrene nanofiber ion exchangers (PSNIE) were fabricated by electrospinning techniques, crosslinking and sulfonation. The degree of crosslinking and the ion exchange capacity (IEC) were determined. The morphology and diameter of the nanofiber mats were analyzed using scanning electron microscopy (SEM). Five cationic model drugs (dextromethorphan, chlorpheniramine, diphenhydramine, propranolol and salbutamol) were loaded into PSNIE. The loading capacity, release and release kinetics of the exchangers were investigated. PSNIE were successfully prepared by electrospinning and were allowed to crosslink for 10 min, resulting in a maximum IEC of 2.86±0.1 meq/g dry PSNIE. The diameter of the fibers after sulfonation was 464±35 nm. Dextromethorphan provided the highest loading in PSNIE while diphenhydramine gave the highest percentage release in both simulated gastric and intestinal fluid (SGF and SIF). The release kinetics of all drugs in SGF and SIF provided the best fit with the particle diffusion model. Our results showed that the development of a PSNIE-based drug delivery system was successful, and PSNIE were able to control drug release.

Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen.

The aim of this study was to prepare novel microemulsion for transdermal drug delivery of ketoprofen (KP). The microemulsion composed of ketoprofen as model drug, isopropyl myristate (IPM) as oil phase, surfactant mixture consisting of polyoxyl 40 hydrogenated castor oil (Cremophor RH40) as surfactant and polyethylene glycol 400 (PEG400) as co-surfactant at the ratio 1:1, and water were prepared. The viscosity, droplet size, pH, conductivity of microemulsions, and skin permeation of KP through shed snake skin were evaluated. The particle size, pH, viscosity and conductivity of microemulsions were in the range of 114-210 nm, 6.3-6.8, 124-799 cPs and 1-45 µS/cm, respectively. The ratio of IPM, and surfactant mixture played the important role in the skin permeation of KP microemulsions. As the amount of surfactant mixture and IPM increased, the skin permeation of KP decreased. The formulation composed of 30% IPM, 45% surfactant mixture and 25% water showed the highest skin permeation flux. The incorporation of terpenes in the 2.5% KP microemulsions resulted in significant enhancement in skin permeation of KP. The rank order of enhancement ratio for skin permeation enhancement of terpenes was α-pinene > limonene > menthone. The results suggested that the novel microemulsion system containing IPM, water, Cremophor RH40:PEG400 and terpenes can be applied for using as a transdermal drug delivery carrier.

Preparation and evaluation of taste-masked dextromethorphan oral disintegrating tablet.

This study was aimed at preparing and evaluating oral disintegrating tablets (ODTs) using a strongly cationic resin, Amberlite(®) IRP-69, to mask the bitter taste of a delivered drug, i..e. dextromethorphan hydrobromide. The drug was loaded into the resin (referred to as resinate) or physically mixed with the resin (referred to as physical mixture), and was then incorporated into ODTs by direct compression. A variety of formulae was developed to acquire the optimal formulations of taste-masked ODTs that had acceptable hardness and mouth feel (grittiness). The optimized ODTs were further evaluated for thickness, diameter, weight, friability, disintegration time, wetting time, wetting rate, drug content, drug release and degree of bitter taste, respectively. The thickness, diameter, weight and friability of the tablet with resinate were slightly higher than those with physical mixture. The tablet with resinate had a longer disintegration time, corresponding with its slower wetting time and rate. Both tablets with resinate and physical mixture provided a sustained pattern of drug release. However, only tablets with resinate successfully masked the bitter taste of the drug. In conclusion, the combination of drug and ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs.

Electrospun poly(vinyl alcohol) fiber mats as carriers for extracts from the fruit hull of mangosteen.

Electrospinning is a process used to produce ultrafine fibers with diameters in the nanometer range. Electrospun fiber mats have high potentials for biomedical uses, due to their high surface area and ease of drug incorporation into the fibers. They can be used as carriers for drug delivery and can enhance drug release and skin permeability. The aim of this study was to prepare electrospun fiber mats and to incorporate extracts from the fruit hull of mangosteen. Antioxidant activity and extract release were determined and compared between the extract incorporated in the electrospun fiber mats and in the cast films. Poly(vinyl alcohol) (PVA) was selected as the polymer matrix. Extracts in the amount of 2.5%, 5%, and 10% w/w, based on the weight of PVA, were incorporated with 10% w/w PVA to finally obtain electrospun fiber mats and cast films. The extract content was evaluated by antioxidative activity using the 2,2-diphenyl-1-picryhydrazyl (DPPH) method. The morphology of the electrospun fiber mats was analyzed using a scanning electron microscope (SEM). The results showed that the diameters of the fibers were in nanoscales and that no crystal of the extract was found at any concentration of the extract. The extract contents in the electrospun fiber mats prepared at 2.5%, 5%, and 10% w/w of the extract were 9.6%, 9.7%, and 10.8% of the initial loading concentration, respectively, whereas, those in the cast films were 23.9%, 14.5%, and 21.0%, respectively. The release of the extract from the electrospun fiber mats prepared at 2.5%, 5%, and 10% w/w of the extract at 120 min were 73.2%, 83.6%, and 81.3% w/w, respectively. However, much slower release from the cast films was observed (i.e., 4.3%, 29.1%, and 40.8% w/w, respectively).

Evaluation of simultaneous permeation and metabolism of methyl nicotinate in human, snake, and shed snake skin.

The transdermal permeation and metabolic characteristics of methyl nicotinate (MN) in stratum corneum and split-thickness human skin and three species of shed snake and snake skin (Elaphae obsoleta, Naja kaouthia, and Python molurus bivittatus) were evaluated. In vitro skin transport using excised skin and hydrolysis experiments using skin homogenate were carried out. The flux of MN, a metabolite, nicotinic acid (NA), and the total (MN+NA), as well as kinetic parameters (V(max) and K(m)) for hydrolysis of MN were determined and compared among various skin types. The total flux from MN-saturated solution through human skin was not significantly different from that through snake and shed snake skin of Elaphae obsoleta, Naja kaouthia but was significantly higher than that through snake and shed snake skin of Naja kaouthia (p < 0.05). A great difference in skin esterase activity was observed between human and snake in both snake skin and shed snake skin of all species. In all skins except the stratum corneum of human skin, NA flux increased with an increase in MN donor concentration and reached a plateau, suggesting that metabolic saturation was taking place in the skin. NA flux at the plateau and MN donor concentrations at which the NA flux reached a plateau also varied by species. These findings indicated that the discrepancy in transdermal profiles of MN among skins tested was predominantly due to the difference in the esterase activity in the skin.

Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies.

Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day(-1)) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P > 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P > 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R(2) > 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies.

Production of monoclonal antibodies against partially purified surface tegument antigens of Fasciola gigantica.

Monoclonal antibodies (MAbs) were produced by the in vitro fusion of Balb/C mice spleen cells immunized with partially purified surface tegument antigens of Fasciola gigantica. The surface membrane and tegument antigens were purified by using gel filtration chromatography. SDS-PAGE performed on the processed proteins demonstrated that the proteins had molecular weights of 20 to 97 kDa. In this study, fifteen monoclonal antibody clones were selected from the hybridoma clones, namely: 1B7, 1B11, 1B12, 1C9, 1D4, 1G2, 1H7, 2B6, 2C3, 2C9, 2D11, 2F11, 2G2, 2G5, and 2G11. They were evaluated by immunoblot assay and were differentiated into two groups. In the first group were found 60 and 38 kDa proteins; in the second group were found 66, 60, and 38 kDa proteins. All were found to secrete IgM, kappa light-chain antibodies. These MAbs were tested for their cross-reactivity with other trematodes commonly found to infect cattle and man. All of these MAbs showed some degree of cross-reactivity with other trematode species.