Fei Han

Preparation, characteristics and assessment of a novel gelatin–chitosan sponge scaffold as skin tissue engineering material

In order to develop a skin tissue engineering material for wound dressing application, a novel gelatin-chitosan sponge scaffold was designed and studied. The effect of chitosan and gelatin ratio on the morphology, pore size, porosity, water uptake capacity, water retention capacity and the degradation behavior were evaluated. Biocompatibility was investigated by both MTT method and AO/EB staining method. Antibacterial assessment and in vivo pharmacodynamic was also studied to evaluate the potential for wound healing. Results showed the sponge scaffold have uniform porous structure with pore size range between 120 and 140 μm, high porosity (>90%), high water uptake capacity (>1500%), high water retention capacity (>400%), and degradation percent in 28 days between 38.3 and 53.9%. Biocompatibility results showed that the activity of cells could not be affected by the nature of the sponge and it was suitable for cell adhesion and proliferation for 21 days. In vivo evaluation indicated that the sponge scaffold could offer effective support and attachment to cells for skin wound healing. In conclusion, the developed sponge scaffold was a potential skin tissue engineering material with appropriate physical properties and good biocompatibility.

Nanostructured lipid carriers (NLC) based topical gel of flurbiprofen: Design, characterization and in vivo evaluation

Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44 μg/ml and 2.49 μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP.

Bicontinuous Water-AOT/Tween85-Isopropyl Myristate Microemulsion: A New Vehicle for Transdermal Delivery of Cyclosporin A

ABSTRACT The purpose of this study was to investigate the influence of structure and composition of microemulsions (AOT/Tween85/isopropyl myristate/water) on their transdermal delivery potential of a lipophilic model drug (Cyclosporin A), and to compare the drug delivery potential of microemulsion to the suspension of drug in normal saline containing 20% ethanol. Their type and structure were examined by measuring surface tension, density, viscometry, and electric conductivity; the degree of agreement between the techniques was assessed. Transdermal flux of Cyclosporin A through rat skin was determined in vitro using Franz-type diffusion cells. Results of conducting, viscosity, and surface tension measurement confirmed the prediction transition to a bicontinuous structure. The microemulsions increased transdermal drug delivery of Cyclosporin A up to 10 times compared to the suspension. The increased transdermal delivery was found to be due mainly to water concentration and appeared to be dependent on the structure of the microemulsions.

Cloud point extraction-HPLC method for determination and pharmacokinetic study of flurbiprofen in rat plasma after oral and transdermal administration

A method based on cloud-point extraction (CPE) was developed for the determination of flurbiprofen (FP) in rat plasma after oral and transdermal administration by high-performance liquid chromatography coupled with UV detection (HPLC-UV). The non-ionic surfactant Genapol X-080 was chosen as the extract solvent. Variables parameter affecting the CPE efficiency were evaluated and optimized. Chromatography separation was performed on a Diamond C(18) column (4.6 mm i.d. x 250 mm, 10 microm particle size) by isocratic elution with UV detection at 254 nm. The assay was linear over the range of 0.2-50 and 0.1-10 microg/ml for oral and transdermal administration, respectively, and the lower limit of quantification (LLOQ) was 0.1 microg/ml. The extraction recoveries were more than 84.5%, the accuracies were within +/-3.8%, and the intra- and inter-day precisions were less than 10.1% in all cases. After strict validation, the method indicated good performance in terms of reproducibility, specificity, linearity, precision and accuracy, and it was successfully applied to the pharmacokinetic study of flurbiprofen in rats after oral and transdermal administration.

Investigation of Nanostructured Lipid Carriers for Transdermal Delivery of Flurbiprofen

The aim of this study was to develop nanostructured lipid carriers (NLC) for transdermal delivery of Flurbiprofen (FP). The physical stability of FP-NLC and its in vitro permeation profile were investigated. After three months of storage at 4°C, 20°C, and 40°C, no significant differences between the evaluated parameters, such as pH value, the entrapment efficiency, particle size, and zeta potential were observed. In in vitro permeation studies, the cumulative permeated amounts and the release rate from FP-NLC were 412.53 ± 21.37 μg/cm2 and 35.25 μg/cm2/h after 12 h (n = 6), respectively, while from saturated FP-PBS (pH = 7.4) were 90.83 ± 8.67 μg/cm2 and 6.99 μg/cm2/h, respectively. These results indicated that the FP-NLC were with good physical stability and were able to improve the permeated amounts and the release rate of FP. It could potentially be exploited as a carrier with improved drug entrapment efficiency and permeated amount in the transdermal delivery of FP.

Self-assembled L-alanine derivative organogel as in situ drug delivery implant: characterization, biodegradability, and biocompatibility.

Objective: The purpose of this work is to prepare and characterize the novel in situ forming implants, obtained through self-assembling of N-stearoyl-L-alanine methyl ester (SAM) in pharmaceutical oils, and to evaluate the biodegradability and biocompatibility of this organogel system. Methods: Minimum gelation concentration was used to measure the gelling ability of gelator SAM in different oils to select the optimal oil for further research. Phase transition temperatures of SAM/soybean oil organogels were determined by differential scanning calorimetry. Comparative studies on the in vitro degradation and in vivo degradation of SAM/soybean oil organogels in mice were investigated. Cytotoxicity tests and histological analysis of SAM/soybean oil organogels were studied by using mouse fibrosarcoma cells and mouse, respectively. Results: As an organogelator, SAM could gel a variety of oils at different minimum gelation concentration. Among them, it had the best-gelling ability in soybean oil, and the SAM/soybean oil organogel could be turned into gels abruptly at body temperature when the concentration of SAM was higher than 5% (w/v) to be used as an injectable system. The in vitro degradation rate of organogel was inversely proportional to the organogelator concentration, whereas the degradation rate in vivo was much higher than in vitro, and gels were almost disappeared after 6 weeks. The selected formulation showed excellent biocompatibility as tested by in vitro cytotoxicity and in vivo histological evaluation. Conclusion: SAM/soybean oil organogel has excellent biodegradability and biocompatibility, which indicates that it has a great potential for safe in situ forming drug delivery.

Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation

Abstract Context: Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery. Objective: An organogel system based on l-lysine derivatives was designed and prepared to induce a thermal sensitive implant with higher transition temperature, better mechanical strength, and shorter gelation time. Materials and methods: The organogel was prepared by injectable soybean oil and methyl (S)-2,5-ditetradecanamidopentanoate (MDP), which was synthesized for the first time. Candesartan cilexetil (CC) was chosen as model drug. Different formulations were designed and optimized by response surface method. Thermal, rheology properties, and gelation kinetics of the optimized formulation had been characterized. The release behaviors in vitro, as well as in vivo were evaluated in comparison with the oily solution of drugs. Finally, the local inflammation response of in situ organogel was assessed by histological analysis. Results and discussion: Results showed that the synthesized gelator, MDP, had a good gelation ability and the organogels obtained via the self-assembly of gelators in vegetable oils exhibited great thermal and rheology properties, which guaranteed their state in body. In vivo pharmacokinetic demonstrated that the organogel formulation could extend the drug release and maintain a therapeutically effective plasma concentration at least 10 d. In addition, this implant showed acceptable moderate inflammation. Conclusion: The in situ forming l-lysine-derivative-based organogel could be a promising matrix for sustained drug delivery of the drugs with low solubility.

Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

Abstract In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle–plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

Studies on the in vitro and in vivo degradation behavior of amino acid derivative-based organogels

Abstract The in vitro degradation behavior of organogel with different gelators based on amino acid was investigated in detail. Two methods were applied in this research: weighting method and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) method, which was established for the first time. Their degradation behaviors in vivo were investigated by varying the kind and concentration of gelators via subcutaneous implantation. The results showed that the stronger the gelation ability or the higher the gelator concentration, the slower the degradation rate of organogel. Moreover, the organogel prepared by oils with longer alkyl length degraded slower than that of the shorter ones, which also decreased in thermal stability and mechanical strength. The investigation on degradation process showed that the degradation rate was mainly controlled by the collapse of network structure formed by gelators. In conclusion, organogel had a tunable degradation rate through altering the gelator type, oil type and the gelator concentration. It remains a promising candidate for subcutaneous in-situ implant as drug delivery vehicle.