<p>Novel chitosan oligosaccharide-based nanoparticles for gastric mucosal administration of the phytochemical “apocynin”</p>

Abstract

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NP s ) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul’s index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NP s formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NP s provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NP s could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.

Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies

“…PDI, based on its value ranging from 0 to 1, has an influence on the therapeutic performance and the pharmacokinetic parameters of the medicated NPs formulations. Both of which are two substantial indicias for estimating size stability of a colloidal dosage form upon storage 2 , 17 .…”

“…On the other hand, positively-charged NPs favour adhesion to the cell mucosa which are normally negatively-charged, hence can be used as mucoadhesive drug delivery systems. As a rule of thumb, absolute ZP values above + 30 mV or below − 30 mV provide very good stability in the dispersion medium 2 , 17 , 48 .…”

“…On the contrary, the amorphous nature of CS (ii) was noticed 59 . STPP (iii) crystallinity was manifested by characteristic peaks at 2θ of 18.826, 19.397, 24.816, 29.664, 33.312, 34.118, and 34.555° 2 . The physical mixture (iv) shows the peaks of CS with clear absence of both ALL and STPP peaks due to their comparatively small amounts.…”

“…The adherence ability of these PNPs to the mucosa and/or their ability to cross the mucosal barrier directly represents an imperative step before the translocation process of particles. From such standpoint, bioadhesion has a pivotal role to play in delivering the loaded drugs across the epithelia, averting presystemic metabolism as well as enzymatic degradation in the GIT 1 , 2 .…”

“…However, several side effects, limited efficacy and elevated incidence of recurrence limited their application and subsequently motivated the search for new safe and effective anti-ulcer therapies. Since gastric ulceration is a multi-etiological disorder, identification of biologically active phytochemicals that possess natural anti-ulcer properties such as the ability to reinforce the defensive endogenous capacity of the gastric mucosa, besides reduction of inflammation and gastric acid secretion may be beneficial in the amelioration of gastric ulcers 2 , 5 .…”