期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 45, 期 7, 页码 1130-1139出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/03639045.2019.1597105
关键词
Benign prostatic hyperplasia; chitosan; doxazosin mesylate; Plackett-Burman design; ionic gelation; hypertension
资金
- Deanship of Scientific Research, King Abdulaziz University, Jeddah [G-465-166-38]
- Deanship of Scientific Research
Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Methods: Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X-1), chitosan percentage (X-2), tripolyphosphate sodium (TPP) percentage (X-3), poloxamer percentage (X-4), homogenization speed (X-5), homogenization time (X-6) and TPP addition rate (X-7). The prepared DM-loaded NPs have been fully evaluated for particle size (Y-1), Zeta potential (Y-2), production yield (Y-3), entrapment efficiency (Y-4), loading capacity (Y-5), initial burst (Y-6), and cumulative drug release (Y-7). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis. Results: The combination of variables showed variability of Y-1, Y-2, and Y-3 equal to 122-710nm, 3.49-23.63 mV, and 47.31-92.96%, respectively. While Y-4 and Y-5, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X-2, X-3, and X-4 are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72 h compared to 4.7 h of drug suspension. Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.
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