چكيده به لاتين
Providing a safe drug delivery system of chitosan, as a natural polymer, and cyanocobalamin with the least amount of additives and in compliance with the biological system to improve the oral administration of drugs with low solubility and permeability was the purpose of this study.
Ciprofloxacin and ticagrelor are two of the drugs in group IV of the biopharmaceutical classification system that have been studied in this project. In order to achieve this goal, the following activities have been performed, respectively:
In order to better drug delivery in the biological system, low molecular weight chitosan was prepared from high molecular weight chitosan using the ultrasonic method, and it was investigated using Fourier-transform infrared spectroscopy, X-ray diffraction, and dynamic light scattering methods.
Due to the inherent advantages of low molecular weight chitosan and cyanocobalamin, and in order to achieve the goal of enhancing drug bioavailability, a conjugate of low molecular weight chitosan and cyanocobalamin was fabricated as a drug carrier and investigated using Fourier-transform infrared spectroscopy, X-ray diffraction, UV-visible, field-emission scanning electron microscopy, and dynamic light scattering methods. The average particle size of the carrier was obtained 81.3 nm and has a zeta potential of +63.4 mV.
In this study, after preparing the drug carrier, ciprofloxacin was loaded on the drug carrier, and the drug loading efficiency was investigated via experimental design using Design-Expert® software and the central composite design method.
Three factors, including the drug carrier concentration, ciprofloxacin concentration, and reaction time, were studied on drug loading efficiency in experimental design. It was obtained that the optimal conditions were 1.5 and 2.5 mg/ml concentrations for the drug carrier and ciprofloxacin, respectively, at 16.25 hours as the reaction time at the constant stirring speed of 350 rpm. Ciprofloxacin loading efficiency in optimal conditions was obtained 57%.
The ciprofloxacin release behavior in two different dissolution media containing phosphate buffer saline (pH=7.4) and hydrochloric acid 0.1 N (pH=1) was investigated. It was observed that the release of ciprofloxacin in both dissolution media was almost similar without any burst release. Ciprofloxacin was completely released within 420 and 600 min, respectively, in 0.1 N HCl and phosphate buffer saline.
The functionalized ciprofloxacin-loaded carrier showed a particle size of about 86.1 nm and zeta potential of +52.9 mV, in which both parameters being useful in drug delivery. Also, in cytotoxicity studies, the ciprofloxacin-loaded carrier showed cytotoxicity of 35, 17, and 23 percent at 100, 10, and 1 μg/ml concentrations, respectively.
In the next step, ticagrelor was loaded on the drug carrier, and chemical and physical specifications of the drug-loaded carrier were investigated. Cytotoxicity of the ticagrelor-loaded carrier was obtained 26, 20, and 11 percent at 100, 10, and 1 μg/ml concentrations, respectively.
Low solubility and permeability are limitations that could restrict the use of different oral dosage forms of ticagrelor, and this formulation was prepared to improve the oral bioavailability of ticagrelor. The ticagrelor-loaded carrier exhibited a high drug loading efficiency that was obtained 80 percent.
The in-vitro release of the ticagrelor-loaded carrier was accomplished in a dissolution medium containing 0.2% w/v polysorbate 80 in deionized water. There isn’t observed any burst release in the drug release assessment, and a controlled drug release pattern was obtained 84.5% within 420 minutes. The particle size of the ticagrelor-loaded carrier was obtained 671 nm using the dynamic light scattering method, and zeta potential of that particles was obtained +54.7 mV.
The results showed that the conjugate of low molecular weight chitosan and cyanocobalamin can be a suitable drug carrier for drug delivery due to the inherent features of the carrier components as well as the desirable properties it has acquired and can be considered as a potential carrier for ciprofloxacin and ticagrelor drug molecules as the drug models.
