Xin Che

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.

The effect of surface charge of glycerol monooleate-based nanoparticles on the round window membrane permeability and cochlear distribution

Abstract The aim of this study is to elucidate the impact of surface charge of glycerol monooleate-based nanoparticles (NPs) on the cellular uptake and its distribution in the cochlea. These NPs are modified using varied concentration of anionic or cationic lipid. Upon dilution, these lipid mixtures self-assemble to form a series of cubic NPs with various surface charges, but with similar particle size. Positively charged NPs exhibited dose-dependent cytotoxicities against L929 cells proportional to the concentration of cationic lipid; whereas negatively charged NPs did not show obvious cytotoxic properties as compared to unmodified NPs. Meanwhile, confocal microscopy and flow cytometry results suggested that NPs with high positive surface charge were taken up more efficiently by L929 cells. The permeability of round window membrane (RWM) was high for highly positively charged NPs, which is likely due to their highly cellular uptake efficiency and consequently high concentration gradient between RWM and cochlear fluid. More importantly, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) modified NPs greatly facilitated broadly distribution in cochlea, favoring the treatment of hearing loss of low frequencies. Taken together, these findings about charge-dependent of NPs on RWM permeability and cochlear distribution could serve as guideline in the rational design of NP for drug and gene delivery to inner ear.

Improved initial burst of estradiol organogel as long-term in situ drug delivery implant: formulation, in vitro and in vivo characterization

Objective: The present investigation was aimed at optimizing of estradiol (E2) loaded l-amino acid derivatives organogel formulations resulting in improved the high initial release problems and sustained release of E2. Methods: The visco-elastic properties of blank organogels were measured by rheometer. The E2 organogel formulations were optimized using a central composite design. Also, the effect of gelator structure and composition of the gel formulations on release behavior (in vitro and in vivo) had been studied. Results: The change of the gelator structure could affect significantly the stiffness of the implants. The release behavior of gel without N-Methyl-2-pyrrolidinone (NMP) was controlled by gel corrosion only. While the drug release of the gel with NMP was controlled by both corrosion and diffusion. The high initial release problems of the organogels were improved by optimizing the formulations. The system consisting by N-Lauroyl l-lysine methyl ester (LLM) derivative in the oil indicated the lowest initial drug release, showed a much lower blood drug level and maintained a steady state for nearly 1 month. Conclusion: Organogels based on l-lysine methyl ester derivative were ideal carriers for long-term parenteral administration of E2.

Xanthoceraside hollow gold nanoparticles, green pharmaceutics preparation for poorly water-soluble natural anti-AD medicine

In order to increase the solubility of poorly water-soluble natural product, xanthoceraside, an effective anti-AD compound from Xanthoceras sorbifolia Bunge, and maintain its natural property, the xanthoceraside hollow gold nanoparticles were successively prepared by green ultrasonic method with silica spheres as templates and HF solution as selective etching solvent. Hollow gold nanoparticles and drug-loaded hollow gold nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The solubilities of xanthoceraside loaded on hollow gold nanoparticles were increased obviously from 3.0μg/ml and 2.5μg/ml to 12.7μg/ml and 10.7μg/ml at 25°C and 37°C, respectively. The results of XRD and DSC indicated that the reason for this increase was mainly due to the amorphous state of xanthoceraside loaded on the hollow gold nanoparticles. In summary, the method of loading xanthoceraside onto hollow gold nanoparticles was a green and useful strategy to improve the solubility and dissolution of poorly water-soluble natural products and worth to applying to other natural products.

Loading and Release of Amine Drugs by Ion-Exchange Fibers: Role of Amine Type

With more production and application of ion-exchange fibers (IEFs), it becomes necessary to understand the interaction between IEFs and amine compounds, an important group of organic drugs and structural components of large organic molecules in biological systems. However, so far few experimental studies have been conducted to systematically investigate the exchanging mechanism of amine compounds to IEFs. Therefore, 15 amine drugs were selected to investigate the effect of amine type on the loading and release of them from the related IEFs. Loading affinity of these drugs by IEFs decreased in the order of secondary, tertiary, and primary. The following items: basicity, aromaticity, molar volume, rotatability, and so on, were emphatically discussed to address the underlying mechanism of drug loading and releasing extent and rate of IEFs. It was evident that strong alkaline drugs strengthened the ionic bond between the amine groups and IEFs, and thus the loading affinity. These results will advance the understanding of the exchanging behavior of IEFs in the drug delivery system.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

A green and facile preparation approach, licochalcone A capped on hollow gold nanoparticles, for improving the solubility and dissolution of anticancer natural product

This study described a valuable drug delivery system for poorly water-soluble anticancer naturalproduct, licochalcone A, isolated from Glycyrrhiza inflata, loaded on hollow gold nanoparticles by green method to improve solubility and dissolution and maintain its natural pharmacological property. Briefly, the formation of hollow gold nanoparticles involves three steps: preparing of silica nanospheres by Stober method, forming of a thick gold shell around the silica templates and etching of silica particles by HF solution. Hollow gold nanoparticles (HGNPs) and drug loaded hollow gold nanoparticles (L-HGNPs) displayed spherical structure and approximately 200nm in size observed by SEM, XRD, EDS and DSC analysis showed that HGNPs were gold hollow structure and crystalline form. The solubility in aqueous solution of licochalcone A was increased obviously to 488.9 μg/ml, compared with free drugs of 136.1 μg/ml. Another interesting finding is that near-infrared (NIR) irradiation increased the speed of solubility of licochalcone A in aqueous solutions, rather than quantity. In short, the method of nano-delivery system combined with poorly water-soluble drug to improve its solubility and dissolution is worth applying to other natural products in order to increase their opportunities in clinical applications.

Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer

Abstract In order to overcome the low compliance due to the frequent bladder perfusion of anti-cancer drugs in the treatment of bladder cancer, a long-term control-release of the anticancer drug in the bladder, the floating intravesical preparation was developed. 5-fluorouracil was used as model drug. The floating preparations were prepared by tableting (mini-tablets) and melting (mini-pellets) method. The proportion of 5-fluorouracil and glyceryl tristearate (GTS) was altered among formulations. Dissolution test, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) were used to investigate the in vitro properties of the formulations. The in vivo evaluation was carried out in beagle dogs. The control-release property of the preparation was not only related to the content of 5-fluorouracil but also related to the preparing method. The releasing time of the mini-tablets was nearly several days, whereas that of the mini-pellets was almost several weeks. DSC and XRPD showed that GTS had polymorphic conversion in the preparing process, therefore, the stabilization procedure was necessary at the end of preparing. In vivo evaluation showed that the prepared long-term floating preparations could maintain an effective 5-fluorouracil concentration in the bladder for about one month, furthermore, in this period the 5-fluorouracil concentration in blood was always far less than that in urine.