Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization, Pharmacodynamics, and Pharmacokinetic Studies
| Autor: | Faisal A. Torad, Nevine Shawky Abdelmalk, Randa latif Aziz, Reham Waheed Hammad, Rania Abdel Baset Sanad |
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| Rok vydání: | 2018 |
| Předmět: |
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medicine.medical_treatment Morpholines Prokinetic agent Pharmaceutical Science Biological Availability 02 engineering and technology Aquatic Science Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo Drug Discovery medicine Animals Particle Size Ecology Evolution Behavior and Systematics Administration Intranasal Drug Carriers Sheep Ecology Gastric emptying Chemistry General Medicine 021001 nanoscience & nanotechnology medicine.disease Mosapride Lipids Bioavailability Nanostructures Nasal Mucosa Gastric Emptying Pharmacodynamics Benzamides GERD Gastroesophageal Reflux Rabbits 0210 nano-technology Agronomy and Crop Science medicine.drug |
| Zdroj: | AAPS PharmSciTech. 19(8) |
| ISSN: | 1530-9932 |
| Popis: | Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Yet, its low solubility and bioavailability due to extensive first-pass metabolism limits its applications. This study aimed to formulate MOS nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its bioavailability. Melt–emulsification low temperature–solidification technique using 23 full factorial design was adopted to formulate MOS-NLCs. Eight formulae were prepared and assessed in terms of entrapment efficiency (%EE), particle size, and in vitro release. Glycerol addition significantly reduced the particle sizes and improved %EE and %drug released. Surface modification using chitosan was applied. The optimized MOS surface-modified nanostructured lipid carriers (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan) showed low particle size 413.8 nm ± 11.46 nm and high %EE 90.19% ± 0.06% and a threefold increase in permeation of MOS with respect to the drug suspension. MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug suspension and commercial product. Statistical analysis revealed a significant increase in gastric emptying rate to be 21.54 ± 1.88 contractions/min compared with10.02 ± 0.62 contractions/min and 8.9 ± 0.72 contractions/min for drug suspension and oral marketed product respectively. Pharmacokinetic studies showed 2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as compared to the oral marketed product. In vitro/in vivo studies proven to level A correlation between in vitro permeation through sheep nasal mucosa and in vivo absorption. Therefore, MOS-SMNLCs could be considered a step forward towards enhancing the clinical efficacy of Mosapride. |
| Databáze: | OpenAIRE |
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