Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of...

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.