طراحی و بررسی خواص فیزیکال فارماسی نانو ذرات آزیترومایسین و کلاریترومایسین

Abstract

The need for intracellular chemotherapy has been recognized for many years. Despite the discovery of new antibiotics, the treatment of intracellular infections often fails completely to eradicate the pathogens. Indeed, the challenge is to design the means of carrying an antibiotic in a form that is able to be endocytosed by phagocytic cells and then release it into these cells. By loading antibiotics into the nanoparticles, one can expect improved delivery to infected cells. The objective of the present study was to prepare Azithromycin and clarithromycin loaded biodegradable nanoparticles, NPS, with a view to investigate the physicochemical properties and anti bacterial activity. PLGA was used as a biodegradable polymer and the particles were prepared by nano-precipitation method in 3 different drug to polymer ratios. Evaluation of the physicochemical properties of the prepared nanoparticles was performed using encapsulation efficiency and dissolution studies, Particle size analysis, zeta potential determination, Differential Scanning Calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffractometry. The antimicrobial activities of azithromycin nanoparticles against Salmonella typhi and clarithromycin nanoparticles against Staphylococcus aureus was determined using serial dilution technique to achieve the Minimum Inhibitory Concentration, MIC, of NPs. The results showed that physicochemical properties of NPs were affected by drug to polymer ratio. The particles were between 189-280nm in size with narrow size distribution, spherical shape and 50.5- 80.2% entrapment efficiency. Zeta () potential of the NPs was fairly negative. The DSC thermograms and X-ray diffraction patterns revealed reduction in crystallinity of drug in the NPs. FT-IR spectroscopy demonstrated no detectable covalent interactions between the drug and polymer. In vitro release study showed two phases an initial burst for 4 hours followed by a plateau during a period of 24 hrs. The NPs were more effective than intact drugs against S. Typhi and S. aureus so that the former showed equal antibacterial effect at 1/8 concentration of the intact drug. In conclusion, the prepared nanoparticles are more potent against the bacterias with improved MICs and appropriate physicochemical properties that may be useful for other susceptible microorganisms and could be an appropriate candidate for intravenous, ocular and oral, administrations. In this study also a novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nanoformulations with total 336 data, gathered from literature. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws.