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.

Fabrication and in-vitro evaluation of ketotifen fumarate-loaded PLGA nanoparticles as a sustained delivery system

Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle [NP] drug delivery system containing ketoftifen, using poly [D,L lactide-co-glycolide] acid [PLGA]. Biodegradable NPs were prepared using 50: 50 PLGA by a water in-oil-in-water [w/o/w] double emulsion-solvent evaporation procedure and characterized for drug content, DSC [differential scanning calorimetry, XRD [X-ray diffractionl], FTIR [Fourier transform spectroscopy], particle size, surface morphology using scanning electron microscopy, and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer [10 mg/mL, 754.6 nm]. Increasing the external organic phase volume [primary emulsion] resulted in larger particles with higher encapsulation efficiency [55%]. The best drug to polymer ratio in the NP was F[3] [1:10 ratio] which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer [1:5] F[1] formulation showed faster dissolution rate than those with high drug to polymer ratio [1:10] F[3] formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h [73.67-90.05%] were obtained

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