A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform

The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was chosen as the model drug. BN –NLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH-and thermo-sensitive hydrogel composed of carboxymethyl chitosan(CMCS) and poloxamer 407(F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin(GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH-and thermo-sensitive. The results of in vitro release suggested BN –NLC gel can prolong the release of baicalin comparing with BN eye drops and BN –NLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient(Papp) of BN –NLC gel was much higher(4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BN –NLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLCbased hydrogel has a promising potential for application in ocular drug delivery.

Influence of hydroxypropyl methylcellulose,methylcellulose, gelatin, poloxamer 407 and poloxamer 188 on the formation and stability of soybean oil-in-water emulsions

Macromolecules of polysaccharides, proteins and poloxamers have a hydrophobic portion and a hydrophilic one that can be used as emulsifiers. Parts of these emulsifiers are safe pharmaceutical excipients, which can replace the irritant low molecular weight surfactants to formulate emulsions for the pharmaceutical field. This project focused on preparing O/W emulsions stabilized with polymers for pharmaceuticals such as polysaccharides, proteins and poloxamers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC),gelatin, poloxamer 407 (F127) and poloxamer 188 (F68). Emulsion physical stability was assessed by centrifugation, autoclaving sterilization and droplet size measurements. The stabilization mechanisms of emulsions were determined by interfacial tension and rheological measurements. Results stated that the efficacy of these polymers for pharmaceuticals stabilized emulsions was sorted in the order: F127 > F68 > HPMC > MC > Gelatin.

Current sustained delivery strategies for the design of local neurotrophic factors in treatment of neurological disorders

Although therapeutic potential of neurotrophic factors(NTFs)has been well recognized for over two decades,attempts to translate that potential to the clinic have been disappointing,largely due to significant obstacles in delivery,including inadequate protein dose/kinetics released at target sites.Considerable efforts have been made to improve the therapeutic performance of NTFs.This articles reviews recent developments in localized delivery systems of NTFs for the neurological disorders treatments with a main focus on sustained delivery strategies.Different non-covalent binding approaches have been employed to immobilize proteins in hydrogels,microspheres,electrospun nanofibers,and their combined systems,which serve as depots for sustained local release of NTFs.The challenges associated with current NTFs delivery systems and how these systems can be applied to neurological diseases and disorders have been discussed in the review.In conclusion,optimal delivery systems for NTFs will be needed for reliable and meaningful clinical benefits;ideally,delivering a time and dose-controlled release of bioactive multiNTFs at different individual optimal kinetics to achieve multi-functions in target tissues is significant preferred.

Association between the physical stability of flurbiprofen suspension and the interaction of HPMC/SDS

The anionic surfactant sodium dodecylsulfate(SDS) has improved the physical stability of flurbiprofen(FBP) suspension, which was suspended by 0.2%(w/v) hydroxypropylmethyl cellulose(HPMC, K4 M). Therefore, the physical stability of FBP suspensions and the interaction of HPMC/SDS were studied, and a certain association between them was revealed. The antisolvent precipitation method was used to prepare suspensions. The apparent drug concentration from different sites was evaluated to get the dispersion of drug actually. The process of flocculation and deflocculation with the addition of SDS was caught by analyzing the morphology of the suspended particles. The physical stability of the FBP suspensions was characterized mainly by measuring the re-dispersion time, the zeta potential and particle size. Meanwhile, conductivity measurements were carried out to obtain the characteristic concentrations of SDS in HPMC/SDS system. The viscosities, the abilities for improving the solubility and wettability of FBP in the separate and mixed HPMC/SDS solutions were also contrasted respectively. The suspensions prepared with HPMC/SDS possessed better physical stability. The suspensions were uniform when the concentration of SDS was between the critical adsorption concentration(CAC) and the polymer saturation point(PSP). After PSP, the uniformity became worse and worse until the SDS was enough to form a deflocculation state. Besides, the re-dispersion time of FBP suspensions was longest when the concentration of SDS around CAC and shorter by shorter after the critical micelle concentration(CMC). The article provided a new sight on the relation between the interaction of excipient matrix and pharmaceutical preparations.

Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws(CMSWs) with ideal topological structures(e.g., small section area, relative rough surface,screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bioadhesion, mucus-penetration and cellular uptake(contributed by the macropinocytosis and caveolaemediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres(CMSSs)and chiral mesoporous silica nanorods(CMSRs), achieving extended retention duration in the gastrointestinal(GI) tract and superior adsorption in the blood circulation(up to 2.61-and 5.65-times in AUC).After doxorubicin(DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier(IEB), and resulted in satisfactory oral bioavailability of DOX(up to 348%).CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.

Preparation and application of mesoporous core-shell nanosilica using leucine derivative as template in effective drug delivery

Core-shell structured mesoporous silica nanoparticles have been firstly synthesized with the new template from L-leucine methyl ester hydrochloride(H-Leu-OMe·HCl).LMSNs were characterized by transmission electron microscopy(TEM),nitrogen adsorption/desorption,and small-angle X-ray diffraction(SAXRD),demonstrating a well-ordered mesostructure.After loading doxorubicin hydrochloride(Dox) into pores,considerable loading capacity of 30.5% and favorable cumulative release amount were obtained.MTT assay suggested that Dox-loaded LMSNs demonstrated great promise to anti-tumor.The use of MSNs with the synthesized template,as a drug delivery carrier,will exte nd the pharmaceutical applications of silica materials.