Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system

Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization.     

Characterization and evaluation of a self-microemulsifying drug delivery system containing tectorigenin,an isoflavone with low aqueous solubility and poor permeability

The purpose of this study was to characterize and evaluate tectorigenin-loaded self-microemulsifying drug delivery system (TG-SMEDDS), a previously studied preparation, and further confirm the improvement of TG in solubility and bioavailability. The appearance of TG-SMEDDS was clear and transparent, with good mobility. The microemulsion formed by TG-SMEDDS was globular, edge smooth, clear-cut, and distribution homogeneous under transmission electron microscope. The stability studies revealed that TG-SMEDDS remained stable at room temperature for at least 3 months. TG-SMEDDS showed excellent dissolution behavior that more than 90% of TG was released in only 5?min. The in situ intestinal perfusion studies indicated enhancement of absorption in four tested intestinal segments, and the main absorption site of TG was changed to duodenum. In addition, TG-SMEDDS showed significantly higher C_max and AUC values (11-fold and 5-fold higher values, respectively; P?AUC_0-t of crude TG and TG-SMEDDS in bile duct non-ligation rats were 6.05 and 2.80 times, respectively, than that in bile duct ligation rats, indicating the existence of enterohepatic circulation and the secretion of bile could significantly affect the absorption of TG. Further studies showed that even the bile duct was ligation, TG-SMEDDS can still keep a better oral bioavailability (179.67%, compared with crude TG in the bile duct non-ligation rats). Therefore, our study implies that SMEDDS containing TG could be an effective strategy for the oral administration of TG.     

Gels and liposomes in optimized ocular drug delivery: studies on ciprofloxacin formulations

Ciprofloxacin (CPFX) containing therapeutic systems were developed using gel- and liposome-based formulations to minimize tear-driven dilution in the conjunctival sac, a long-pursued objective in ophthalmology. Physicochemical properties (pH, osmolarity, viscosity, expansivity, membrane fluidity and in vitro CPFX release rate) of the preparations were studied by the appropriate methods. For gel preparation, the bio-adhesive poly(vinyl alcohol) and polymethacrylic acid derivatives were applied in various concentrations. In our liposome-supported carrier systems, multilamellar vesicles from lecithin and alpha-L-dipalmithoyl-phosphatidylcholine provided the encapsulating agent. Electron paramagnetic resonance (EPR) spectroscopy was applied to study the molecular interactions in the ophthalmic formulations. The polymer hydrogels used in our preparations ensured a steady and prolonged active ingredient release. In addition, encapsulation of the CPFX into liposomes prolonged the in vitro release of the antibacterial agent depending on the lipid composition of the vesicles.     

眼部的给药屏障和给药途径

近年来,眼部药物递送系统越来越受到重视,本文综述了目前眼部给药的主要屏障包括角膜、结膜屏障,血房水屏障、血视网膜屏障等,以及一些新的给药途径和给药方法如结膜下、巩膜给药和离子电渗疗法等。以环孢素A为例介绍了一些克服眼部屏障的给药方法。尽管眼部给药系统目前已取得了进展,但药物递送到眼的后段仍有较大的难度,需要进一步开发更有效的眼部药物递送系统。     

Ion- and pH-activated novel in-situ gel system for sustained ocular drug delivery

Poor bioavailability (<1%) of drugs from conventional eye drops is mainly due to the various precorneal loss factors which include rapid tear turnover, systemic drug absorption through naso-lachrymal duct, transient residence time of the drug solution in the cul-de-sac and the relative impermeability of the drugs to corneal epithelial membrane. The present study describes the formulation and evaluation of chitosan and gellan gum based novel in-situ gel system activated by dual physiological mechanisms. Chitosan (a pH-sensitive polymer) in combination with gellan gum (an ion-activated polymer) were used as gelling agent. Timolol maleate, the drug which is frequently used for glaucoma therapy was used as model drug to check the efficacy of the formulation. The developed formulation was characterized for various in vitro parameters, for example, clarity, gelation pH, isotonicity, sterility, viscosity, transcorneal permeation profile, and ocular irritation. Ocular retention was studied by gamma scintigraphy and a significant increase in retention time was observed. The formulation was also found to be nonirritant and well tolerable. The developed system can be a viable alternative to conventional eye drops for the treatment of various ocular diseases and is suitable for clinical application.     

智能药物传输系统的研究进展

智能药物传输系统是指系统自身具有传感、处理及响应释药、停止释药的"自动"药物传输体系。各种智能药物传输系统实现了药物的定点、定时及定量释放。简要介绍了智能药物传输系统的发展近况,并从pH值敏感型、温度敏感型、葡萄糖敏感型以及其他敏感型给药系统角度阐述了智能药物传输系统的研究现状及未来展望。     

Design and characterization of colon-specific drug delivery system containing paracetamol microsponges

The present work was aimed at designing microsponge based colon specific drug delivery system containing paracetamol. Eudragit S-100 based microsponges containing drug in varying amounts were prepared using quasi-emulsion solvent diffusion method. The microsponges were prepared by optimizing various process parameters. DSC and FTIR studies indicated compatibility of the drug in various formulations. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies and the results were evaluated kinetically and statistically. The in vitro release data showed a bi-phasic pattern with an initial burst effect. In the first hour drug release from microsponges was found to be between 18-30%. The cumulative percent release at the end of 12(th) hour was noted to be between 74-98%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion. The colon specific tablets were prepared by compressing the microsponges followed by coating with pectin: hydroxypropylmethyl cellulose (HPMC) mixture. In vitro release studies exhibited that compression coated colon specific tablet formulations started releasing the drug at 6(th) hour corresponding to the arrival time at proximal colon. The study presents a new approach for colon specific drug delivery.     

脂质体经皮给药研究进展

目的:分析总结近年来国外脂质体经皮或黏膜给药研究的特点和应用进展。方法:对近年来脂质体药物特点,主要对在皮肤疾病和美容方面,对局部伤口的治疗,在皮肤损伤和保护中的应用,在眼科疾病中的应用进行综述。结果与结论:脂质体是一种很好的定向药物载体,它的应用范围将越来越广     

Preparation,characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system

This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(ζ )-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive ζ -potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components.     

Evaluation of powder mixtures and hydrophilic gastroretentive drug delivery systems containing zinc acetate and sodium bicarbonate

The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated.     

Pluronic F127-based ocular delivery system containing biodegradable polyisobutylcyanoacrylate nanocapsules of pilocarpine

The objectives of our study were to prepare a biodegradable polyisobutylcyanoacrylate (PIBCA) colloidal particulate system of pilocarpine, to incorporate it into a Pluronic F127(PF127)-based gel delivery system, and to evaluate its ability to prolong the release of pilocarpine. Polyisobutylcyanoacrylate nanocapsules (PIBCA-NC) of pilocarpine were prepared by interfacial polymerization. Physicochemical characterization of the colloidal dispersion of PIBCA-NC of pilocarpine was performed by measuring drug loading, particle size analysis, and scanning electron microscopy. Results indicated that approximately 13.5% of pilocarpine was loaded onto the PIBCA-NC, the nanocapsules ranged from 370 to 460 nm, the distribution was narrow, and there was no significant effect of stirring speed on particle size. The PIBCA-NC dispersion of 1% pilocarpine alone (I) and after incorporation into the Pluronic F127 gel delivery system (II) were compared against 1% pilocarpine incorporated into a PF127 gel containing 5% methylcellulose (PF127MC) alone (III) by measuring the miotic response in the albino rabbit eye. Statistical analysis indicated a rank-order for both the duration and intensity of miosis of II > III > I, with all differences being significant (p < 0.05). Thus, it appears that II increases the contact time of pilocarpine with the absorbing tissue in the eye, thereby improving ocular bioavailability. The PIBCA-NC of pilocarpine dispersed in the PF127MC gel delivery system has considerable potential for achieving a prolonged delivery for such drugs as pilocarpine and other more hydrophobic drugs.     

Design and evaluation of colon specific drug delivery system containing flurbiprofen microsponges

The purpose of this study was to design novel colon specific drug delivery system containing flurbiprofen (FLB) microsponges. Microsponges containing FLB and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. Additionally, FLB was entrapped into a commercial Microsponge 5640 system using entrapment method. Afterwards, the effects of drug:polymer ratio, inner phase solvent amount, stirring time and speed and stirrer type on the physical characteristics of microsponges were investigated. The thermal behaviour, surface morphology, particle size and pore structure of microsponges were examined. The colon specific formulations were prepared by compression coating and also pore plugging of microsponges with pectin:hydroxypropylmethyl cellulose (HPMC) mixture followed by tabletting. In vitro dissolution studies were done on all formulations and the results were kinetically and statistically evaluated. The microsponges were spherical in shape, between 30.7 and 94.5microm in diameter and showed high porosity values (61-72%). The pore shapes of microsponges prepared by quasi-emulsion solvent diffusion method and entrapment method were found as spherical and cylindrical holes, respectively. Mechanically strong tablets prepared for colon specific drug delivery were obtained owing to the plastic deformation of sponge-like structure of microsponges. In vitro studies exhibited that compression coated colon specific tablet formulations started to release the drug at the 8th hour corresponding to the proximal colon arrival time due to the addition of enzyme, following a modified release pattern while the drug release from the colon specific formulations prepared by pore plugging the microsponges showed an increase at the 8th hour which was the time point that the enzyme addition made. This study presents a new approach based on microsponges for colon specific drug delivery.     

Self nano-emulsifying drug delivery system for Embelin: Design,characterization and in-vitro studies

CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90), X2 (amount of surfactant; Acrysol EL 135) and X3 (amount of co-surfactant; PEG 400). Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS) by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.     

Challenges and obstacles of ocular pharmacokinetics and drug delivery

Modern biological research has produced increasing number of promising therapeutic possibilities for medical treatment. These include for example growth factors, monoclonal antibodies, gene knockdown methods, gene therapy, surgical transplantations and tissue engineering. Ocular application of these possibilities involves drug delivery in many forms. Ocular drug delivery is hampered by the barriers protecting the eye. This review presents an overview of the essential factors in ocular pharmacokinetics and selected pharmacological future challenges in ophthalmology.     

口服生物黏附微粒释药系统的研究现状

口服生物黏附微粒释药系统是通过黏附聚合物的使用,使各种药物存留在上皮细胞膜上的时间延长从而提高生物利用度.本文就生物黏附微粒系统的材料、制备方法、性能评价等方面进行综述.     

Formualtion and evaluation of floating drug delivery system containing clarithromycin for Helicobacter pylori

Floating matrix tablets are designed to prolong the gastric residence time after oral administration, at a particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. With this objective, floating dosage form containing clarithromycin as drug was designed for the treatment of Helicobacter pylori. Tablets containing hydroxypropylmethylcellulose (HPMC), drug and different additives were compressed using wet granulation and D-optimal design technique. The study shows that tablet composition and mechanical strength have great influence on the floating properties and drug release. Incorporation of gas-generating agent together with polymer improved drug release, besides optimal floating (floating lag time < 30 s; total floating time > 10 h). The drug release was sufficiently sustained (more than 8 h) and anomalous diffusion as well as zero-order was confirmed. Optimization of the evaluating parameters with 'design expert' software was employed to get final optimized formulation. The optimized formulation was obtained using 62.5% clarithromycin, 4.95% HPMC K15M, 18.09% HPMC K4M, 12.96% sodium bicarbonate which gave floating lag time < 30 s with a total floating time > 10 h, in vitro release profile very near to the target in vitro release profile and follows anomalous diffusion as well as zero order pattern of release.     

Low molecular weight chitosan-coated liposomes for ocular drug delivery: in vitro and in vivo studies

In this study, low molecular weight chitosan coated liposomes (LCHL) were designed and prepared for ocular drug delivery, the coating mechanism was studied, and in vitro and in vivo characterization was conducted. The effects of molecular weight and concentration of low molecular weight chitosan on the liposomal coating were studied. The numeric relations between coating variables and coating efficiency were established using a mathematical model. Morphology of LCHL was examined by transmission electron microscopy (TEM). Cytotoxicity and cell internalization of FITC-BSA labeled LCHL in a rabbit conjunctival epithelium (RCE) cell line were studied. Cyclosporin A (CsA) was encapsulated as a model drug, and in vitro drug release and in vivo drug absorption were investigated. LCHL demonstrated low toxicity to RCE cells. In vitro drug release measurement showed that LCHL had a delayed release profile compared with non-coated liposomes. In vivo study in rabbits showed that the concentrations of CsA in cornea, conjunctiva, and sclera were remarkably increased by LCHL. In conclusion, LCHL might be a potential ocular drug carrier with characteristics such as prolonged drug retention, enhanced drug permeation, and biocompatibility.