Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug.

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.

Hybrid polymeric microspheres for enhancing the encapsulation of phenylethyl resorcinol.

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release.

Houttuynia cordata (H. cordata) has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs) were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin) were 92.9-95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.

Ethosomes and Transfersomes for Topical Delivery of Ginsenoside Rhl from Red Ginseng: Characterization and In Vitro Evaluation.

Red ginseng (the steamed root of Panax ginseng C. A. Mayer), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Ginsenoside Rhl, a bacterial metabolite of ginsenoside Rgl, is a protopanaxatriol type of ginsenosides. Liposomes do not deeply penetrate the skin and remain confined to the stratum corneum.Thus, new vesicular colloidal carriers such as ethosomes and transfersomes have been developed as an enhanced type of liposomes, recently. The aim of this study was to improve the topical delivery of ginsenoside Rhl isolated from red ginseng employing new vesicular system of ethosomes and transfersomes compared to conventional liposome. Characterization of ginsenoside Rhl-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (% EE), and transmission electron microscopy (TEM) studies. In addition, skin permeation profile was obtained using frantz diffusion cells and rat dorsal skin treated with ethosome and transfersome compared with conventional iposome. The size of vesicles range from 108.5 to 322.9 nm, and negatively charged from -20.95 to -31.37 mV. The % EE of ginsenoside Rh1 was obtained between 45.0 to 65.0%. Transfersomes provided a significantly higher skin permeation of ginsenoside Rhl compared to ethosome and conventional liposome. Therefore, based on the current study, ginsenoside Rhl-loaded transfersomes can act as a topical therapeutic effects potential.

Enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on Eudragit® e.

The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 µg/mL within 0.5 h that gradually decreased to 173.4 µg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.

Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA Particles.

It is known that allergic people was potentially vulnerable to bee venom (BV), which can induce an anaphylactic shock, eventually leading to death. Up until recently, this kind of allergy was treated only by venom immunotherapy (VIT) and its efficacy has been recognized worldwide. This treatment is practiced by subcutaneous injections that gradually increase the doses of the allergen. This is inconvenient for patients due to frequent injections. Poly (D,L-lactide-co-glycolide) (PLGA) has been broadly studied as a carrier for drug delivery systems (DDS) of proteins and peptides. PLGA particles usually induce a sustained release. In this study, the physicochemical properties of BV were examined prior to the preparation of BV-loaded PLGA nanoparticles NPs). The content of melittin, the main component of BV, was 53.3%. When protected from the light BV was stable at 4 °C in distilled water, during 8 weeks. BV-loaded PLGA particles were prepared using dichloromethane as the most suitable organic solvent and two min of ultrasonic emulsification time. This study has characterized the physicochemical properties of BV for the preparation BV-loaded PLGA NPs in order to design and optimize a suitable sustained release system in the future.

Surface-modified gemcitabine with mucoadhesive polymer for oral delivery.

Gemcitabine microparticles were prepared using chitosan, polyethylene oxide or carbopol as the mucoadhesive polymer and eudragit L100-55 as the enteric polymer by a double emulsion method. The particle size and zeta potential changed from 1338.3 ± 254.1 nm to 2459.4 ± 103.6 nm and -5.16 ± 1.62 mV to 2.84 ± 0.65 mV, respectively, with increasing chitosan to gemcitabine weight ratio from 0.25 to 1. The gemcitabine-loaded microparticles without mucoadhesive polymer (F50) showed the particle size and zeta potential of 671.3 ± 58.3 nm and - 16.7 ± 1.82 mV, respectively. The cellular uptake of gemcitabine into Caco-2 cells from gemcitabine-loaded microparticles with chitosan increased with increasing incubation time in Caco-2 cells compared to that of gemcitabine-loaded microparticles with polyethylene oxide or carbopol, suggesting that chitosan might be the optimal mucoadhesive polymer. Gemcitabine microparticles will be tested to identify whether the oral absorption could be increased in the future.

Mannosylated poly(acrylic acid)-coated mesoporous silica nanoparticles for anticancer therapy.

Although mesoporous silica nanoparticles (MSNs) are widely used as anticancer drug carriers, unmodified MSNs induce off-target effects and at high doses, there are adverse effects of hemolysis because of the interaction with the silanol group on the surface and cells. In this study, we developed doxorubicin (DOX)-loaded MSNs coated with mannose grafted poly (acrylic acid) copolymer (DOX@MSNs-man-g-PAA) to enhance the hemocompatibility and target efficacy to cancer cells. This uniform nanosized DOX@MSNs-man-g-PAA showed sustained and pH-dependent drug release with improved hemocompatibility over the bare MSNs. The uptake of the DOX@MSN-man-g-PAA in breast cancer cells was significantly improved by mannose receptor-mediated endocytosis, which showed significant increasing intracellular ROS and changes in mitochondrial membrane potential. This formulation exhibited superior tumor-suppressing activity in the MDA-MB-231 cells inoculated mice. Overall, the present study suggested the possibility of the copolymer-coated MSNs as drug carriers for cancer therapy.

Enhanced local anesthetic action of mepivacaine from the bioadhesive gels.

Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain. Among the many drug delivery systems, transdermal drug delivery has some advantages, as it provides controlled drug delivery for an extended period of time. To develop new gel formulations that have suitable bioadhesion, the bioadhesive force of hydroxypropyl methylcellulose (HPMC) was assessed using an auto-peeling tester. The effect of drug concentration on drug release from 2% HPMC gel was studied using synthetic cellulose membrane at 37±0.5°C. The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and 42°C. To increase the skin permeation of mepivacaine from HPMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug permeation was then examined in the modified Keshary-Chien cell. For the efficacy study, the anesthetic action of the formulated mepivacaine gel containing enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive forces increased. Increasing the drug concentration or temperature increased the drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancement of permeation. Based on the area under the efficacy curve of the rat tail flick test curve, mepivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased local anesthetic action compared to the control. For bioadhesive mepivacaine gels with enhanced local anesthetic action, mepivacaine gels containing penetration enhancer and vasoconstrictor could be developed with the bioadhesive polymer, HPMC.

Novel self-floating tablet for enhanced oral bioavailability of metformin based on cellulose.

Metformin has several problems such as low bioavailability, short half-life, and narrow absorption window, sustained and site-specific drug delivery system is required. Floating drug delivery systems are very useful to achieve these purposes. However, conventional floating systems have several limitations; lag time, a high proportion of excipient in the tablet, using non-biocompatible excipient, and requirement of a complicated procedure. To overcome these obstacles, we developed a hollow-core floating tablet (HCFT). The HCFT immediately floated in pH 1.2, 4.0, 6.8 medium, and even distilled water. The floating duration time of HCFT was>24 h. From the in vitro release study, it was confirmed that HCFT showed the sustain release profile of metformin for 12 h. Water uptake and matrix erosion were evaluated for predicting the buoyancy and drug release kinetics of HCFT in the body. Factor analysis was applied to optimize the formulation. There were significant (p < 0.05) differences in metformin plasma concentration of 4 h and 6 h between two groups. Compared with Glucophage® XR, the relative bioavailability of metformin HCFT was 123.81 ± 3.52%. The X-ray imaging of optimized formulation revealed that HCFT was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention for>6 h. Consequently, all the findings indicate that HCFT could be an effective gastric retention system and applied extensively to other drugs with narrow absorption windows.

Development and evaluation of TPGS/PVA-based nanosuspension for enhancing dissolution and oral bioavailability of ticagrelor.

In this study, we developed ticagrelor-dispersed nanosuspension (TCG-NSP) to enhance the dissolution and oral bioavailability of ticagrelor (TCG) through a statistical design approach. TCG, a reversible P2Y12 receptor antagonist, is classified as a biopharmaceutics classification system (BCS) class IV drug with low solubility and permeability, resulting in low oral bioavailability. Nanosuspension (NSP) is an efficient pharmaceutical technique for overcoming the disadvantages. First, we optimized TCG-NSP consisting of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl alcohol (PVA), which exhibited homogeneously dispersed TCG particle (233 nm) and low precipitation (3%). Characterization studies demonstrated that TCG-NSP provided amorphous TCG particles and supersaturation effect, resulting in higher dissolution than a commercial product. In addition, everted gut sac and pharmacokinetic studies confirmed that TCG-NSP improved the gastrointestinal permeation of TCG by 2.8-fold compared to commercial product, thereby enhancing the oral bioavailability (2.2-fold). These results suggested that TCG-NSP could be successfully used as an efficient pharmaceutical formulation to achieve the enhanced dissolution and oral bioavailability of TCG.

Enhanced transdermal absorption and pharmacokinetic evaluation of pranoprofen-ethylene-vinyl acetate matrix containing penetration enhancer in rats.

To increase the skin permeation of pranoprofen from the ethylene-vinyl acetate (EVA) matrix, different types of enhancers were added to an EVA matrix containing 2% pranoprofen. The pharmacokinetics and bioavailability of pranoprofen, an anti-inflammatory drug, were examined to determine the feasibility of an enhanced transdermal delivery system for pranoprofen from an EVA matrix containing caprylic acid as the enhancer in rats. The effects of the enhancers on the level of pranoprofen permeation through the skin were evaluated using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, including the fatty acids (saturated, unsaturated), the glycols, the glycerides, and the pyrrolidones, caprylic acid showed the best enhancement. A pranoprofen-EVA matrix system was formulated containing caprylic acid as an enhancer. The pranoprofen-EVA matrix system (8 mg/kg) was applied to the abdominal skin of rats. The blood samples were collected through the femoral artery for 24 h and the plasma concentrations of pranoprofen were determined by HPLC. The pharmacokinetic parameters were calculated using the MULTI computer program. The area under the curve (AUC) was significantly higher in the enhancer group (55.49 +/- 13.87 ng/mL.h) than in the control group (22.48 +/- 5.63 ng/mL.h), which was treated transdermally without the enhancer, showing about 246% increased bioavailability (p<0.05). As the pranoprofen-EVA matrix containing caprylic acid as an enhancer was administered to rats via the transdermal routes, the relative bioavailability increased about 2.46-fold compared to the control group, showing a relatively constant, sustained blood concentration. These results show that a pranoprofen-EVA matrix containing a permeation enhancer could be developed as a transdermal delivery system to provide a sustained plasma concentration.

Statistical approach for solidifying ticagrelor loaded self-microemulsifying drug delivery system with enhanced dissolution and oral bioavailability.

The aim of this study was to solidify a ticagrelor loaded self-microemulsifying drug delivery system (TCG-SM) with enhanced dissolution and bioavailability of ticagrelor (TCG) for developing TCG-SM granules and tablets. TCG was dissolved in the self-microemulsifying drug delivery system (SMEDDS) and TCG-SM was solidified by adsorption to the optimized adsorbent through statistical design. In order to select an appropriate adsorbent, the physical properties (bulk density, tapped density, angle of repose, and liquid adsorption capacity) of silica-based adsorbents (Neusilin US2, Florite R, Aerosil 200, and Florite PS-10) and non silica-based adsorbents (Avicel PH102, Pharmatose 100M, Pearlitol 200, LH-11, and Emcompress) were investigated. Neusilin US2 and Florite R were selected as suitable adsorbents and their mixing ratios were optimized using statistical experimental design. The predicted values of physical properties by statistical design showed the error percentage of <10% compared to actual values. As a result of the statistical approach, TCG-SM (490 mg) was successfully solidified with Nesulin US2 (167.8 mg) and Florite R (82.2 mg), which showed good powder properties and improved dissolution of TCG. The solidified TCG-SM (Sol-TCG-SM), disintegrant (croscarmellose sodium), diluent (microcrystalline cellulose), binder (polyvinylpyrrolidone), and lubricant (magnesium stearate) were mixed to prepare granules. And, the granules with total weight of 900 mg were tableted using 16 mm oval-shape punch. The prepared Sol-TCG-SM tablet showed good tablet properties and maintained self-microemulsifying ability, such as microemulsion formation and enhanced dissolution of TCG. In vivo pharmacokinetic study, the relative bioavailability of Sol-TCG-SM exhibited 108.1% and 632.7% compared to TCG-SM and raw TCG powder, respectively. In conclusion, we successfully solidified SMEDDS with improved oral bioavailability of insoluble drugs such as TCG through a statistical design. This suggests a new approach that can be utilized in the production of solidified SMEDDS.

Surface modification of paclitaxel-loaded liposomes using d-α-tocopheryl polyethylene glycol 1000 succinate: Enhanced cellular uptake and cytotoxicity in multidrug resistant breast cancer cells.

Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer drug for the treatment of various cancers. However, paclitaxel has a solubility of 0.5 mg/L in water and a low bioavailability of 6.5%. Moreover, paclitaxel is a substrate for p-glycoprotein, which shows a decreased accumulation of drug within the cancer cell expressed by a p-glycoprotein. Therefore, the purpose of this study is to prepare a paclitaxel-loaded liposome and evaluate the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an inhibitor of p-glycoprotein on the paclitaxel-loaded liposome. The paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome had spherical vesicles, with mean particle size 184.9 ±â€¯18.45 nm with PDI 0.324 ±â€¯0.018 and 282.6 ±â€¯20.41 nm with PDI 0.269 ±â€¯0.013, respectively. Paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome showed a controlled and sustained release of PTX over 72 h. The cellular uptake of paclitaxel from TPGS coated paclitaxel-loaded liposome was a 3.56-fold increase for 2 h and 5.75-fold increase for 4 h compared to that from paclitaxel-loaded liposome in MCF-7/ADR cells, resulting in improved cytotoxicity against MCF-7/ADR cells. Western blot assay revealed the P-gp inhibitory effect of TPGS-coated PTX-liposome. In conclusion, TPGS coated liposome with a sustained releasing capability and the inhibitory effect of p-glycoprotein may be a promising carrier for future applications in cancer therapy.

Physicochemical characteristics of quinupramine in the EVA matrix.

Ethylene-vinyl acetate (EVA) is widely used as a membrane or matrix for transdermal drug delivery systems. In an attempt to determine the state of a drug in the EVA matrix, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermal analysis of the quinupramine-EVA matrix were carried out and the results were compared with those of a physical mixture of quinupramine and EVA at the same ratio. The 1:2 matrix of quinupramine with EVA was prepared using the casting method. The XRD pattern of the quinupramine test preparations revealed that the pure quinupramine was crystalline in nature, whereas the quinupramine in the EVA matrix was an amorphous form, which leads to increased drug release. The FT-IR spectra of quinupramine in the physical mixture showed absorption bands at around 3000-3050 cm(-1) whereas these absorption bands were not observed in the quinupramine-EVA matrix. The thermal studies of quinupramine in the physical mixture showed an endothermic peak at 154-156 degrees C, which is the melting point of the drug, but there was no such endothermic peak observed in the EVA matrix. In conclusion, the physicochemical interactions between quinupramine and EVA, might occur at the molecular level, and that quinupramine was not crystalline in the EVA matrix.

Release characteristics of quinupramine from the ethylene-vinyl acetate matrix.

An ethylene-vinyl acetate (EVA) matrix containing quinupramine was prepared in an attempt to develop a controlled delivery system for quinupramine. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of quinupramine from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, membrane thickness, drug concentration, temperature, and plasticizer on drug release rate were investigated. The drug release rate from the EVA matrix increased with increasing PEG 400 volume fraction, temperature and drug loading dose. The activation energy for drug release was 5.91, 5.39, 4.68 and 4.52 kcal/mol for a loading dose of 0.5%, 1%, 1.5%, and 2%, respectively. Among the plasticizers used, diethyl phthalate showed the best results. The release of quinupramine from the EVA matrix follows a diffusion-controlled model, where the quantity released per unit area is proportional to the square root of time. The controlled release of quinupramine was achieved using the EVA polymer including a plasticizer.

Enhanced transdermal delivery of pranoprofen from the bioadhesive gels.

Percutaneous delivery of NSAIDs has advantages of avoiding hepatic first pass effect and delivering the drug for extended period of time at a sustained, concentrated level at the inflammation site that mainly acts at the joint and the related regions. To develop the new topical formulations of pranoprofen that have suitable bioadhesion, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer 407. The effects of temperature on drug release was performed at 32 degrees C, 37 degrees C and 42 degrees C according to drug concentration of 0.04%, 0.08%, 0.12%, 0.16%, and 0.2% (w/w) using synthetic cellulose membrane at 37+/-0.5 degrees C. The increase of temperature showed the increased drug release. The activation energy (Ea), which were calculated from the slope of lop P versus 1000/T plots was 11.22 kcal/ mol for 0.04%, 10.79 kcal/mol for 0.08%, 10.41 kcal/mol for 0.12% and 8.88 kcal/mol for 0.16% loading dose from the pranoprofen gel. To increase the drug permeation, some kinds of penetration enhancers such as the ethylene glycols, the propylene glycols, the glycerides, the non-ionic surfactants and the fatty acids were incorporated in the gel formulation. Among the various enhancers used, propylene glycol mono laurate showed the highest enhancing effects with the enhancement factor of 2.74. The results of this study suggest that development of topical gel formulation of pranoprofen containing an enhancer is feasible.

Transdermal delivery of tadalafil using a novel formulation.

The aim of this work was to investigate the transdermal gel loaded with tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5) in order to improve the solubility and bioavailability. The solubility of tadalafil in mixed solution of hydroxypropyl-ß-cyclodextrin (HPCD), polyethylene glycol (PEG) 400 and tween 80 (T2 solution) was 260.8 ± 4.3 µg/mL and that of tadalafil in modified T2 (M-T2) solution, which tadalafil was dissolved in 20% (w/v) HPCD at first and then mixture solutions of PEG 400 and tween 80 were added, was increased to 344.9 ± 30.6 µg/mL. Four gel formulae were prepared, subsequently in vitro and in vivo skin permeation studies were carried out. Interestingly, tadalafil gel in M-T2 and oleic acid (OA) (F3) could promote the percutaneous absorption of tadalafil by 179.4% in vitro and increase AUC by 223% in vivo compared with tadalafil gel in the absence of M-T2 and OA (F1). Also, there was a finding that tadalafil gel in M-T2 and OA did not cause dermal irritations in an experimental animal.

Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local intestinal immune responses in weaned pigs.

Nasal delivery is a convenient and acceptable route for drug administration, and has been shown to elicit a much more potent local and systemic response compared with other drug delivery routes. We previously demonstrated that rectal administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV) could enhance systemic Th 1-specific immune responses. We therefore synthesized chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of nasally administered CP-HBV on systemic and local intestinal immunity compared with non-chitosan-coated P-HBV. The nasally delivered CP-HBV effectively enhanced Th 1-specific responses, eliciting a significant increase in the CD3(+)CD4(+)CD8(-) Th cell population, lymphocyte proliferation capacity, and expression of Th 1 cytokines (IFN-γ, IL-12, and IL-2) in peripheral blood mononuclear cells. Furthermore, these immune-boosting effects persisted up to 21days post CP-HBV administration. Nasal administration of CP-HBV also led to an increase of not only the CD4(+) Th 1 and IFN-γ secreting CD4(+) Th 1 cell population but also Th 1-specific cytokines and transcription factors, including IL-12, IFN-γ, STAT4, and T-bet, in isolated mononuclear cells from the spleen and ileum.