Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding  and  cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on  and  models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

Statistical optimization of oral vancomycin-eudragit RS nanoparticles using response surface methodology

A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin [VCM] nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM [X1], amount of emulsifier [X2], stirring rate [X3], volume of organic phase [X4] and volume of aqueous phase [X5], on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 [%w/w] amount of emulsifier, 25 mL [volume of organic phase], 25 mL [volume of aqueous phase], 3 min [time of stirring] and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading [R2 = 90.82]. The highest entrapment efficiency was obtained when the ratio of drug to polymer was 1:3. Zeta [zeta] potential of the nanoparticles was fairly positive in molecular level. In vitro release study showed two phases: an initial burst for 0.5 h followed by a very slow release pattern during a period of 24 h. The release of VCM was influenced by the drug to polymer ratio and particle size and was found to be diffusion controlled. The best-fit release kinetic was achieved with Peppas model. In conclusion, the VCM nanoparticle preparations showed optimize formulation, which can be useful for oral administrations

Preparation and evaluation of poly [epsilon-caprolactone] nanoparticles-in-microparticles by W/O/W emulsion method

Theophylline, a xanthenes derivative, is still widely used as an effective bronchodilator in the management of asthmatic patients. It is used both as a prophylactic drug and to prevent acute exacerbations of asthma. The aim of study was to formulate and evaluate effect of the microencapsulation of theophylline loaded nanoparticles on the reduction of burst release. Microparticles [simple and composite] and nanoparticles were prepared by using water-in-oil-in-water [W[1]/O/W[2] double-emulsion solvent diffusion/evaporation method], taking different ratios of drug/polymer. Solvent systems consist of ethyl acetate and dichloromethane for microspheres and nanospheres, respectively. In the current study formulations were characterized by loading efficiency, yield, particle size, zeta potential, X-ray diffraction [XRD] and differential scanning calorimetry [DSC]. In microparticles, the best drug to polymer ratio was 0.8:1 [F[3]]. F[3] formulation had minimum burst effect [37.81%], high loading efficiency [95.88%]. In nanoparticles, F[4] formulation [0.4:1 drug/polymer ratio] showed high production yield [40.8%], loading efficiency [99.05%], low particle size [756 nm] and minimum burst effect compared with other nanoparticle formulations. The drug loaded composite microspheres [F[9]] showed minimum burst effect, acceptable release and mean particle size 17.696 micro m. The XRD and DSC showed stable character of theophylline in the drug loaded microspheres. The drug release was found to be diffusion and erosion controlled. The burst was significantly lower with composite microparticles and may be explained by lower diffusion of the drug from double polymeric wall formed by the nanoparticles matrix followed by another diffusion step through the microparticle polymeric wall