Chitosan-coated Alginate (CCA) Nanoparticles for Augmentation of Topical Antihistaminic Activity of Diphenhydramine: In-Vitro Optimization, Skin Histopathology and Pharmacodynamic Studies with in Vitro/in Vivo Correlation.

ObjectiveThe aim of the present study was to formulate chitosan-coated alginate nanoparticles containing the drug diphenhydramine hydrochloride (DHH).SignificanceDiphenhydramine hydrochloride (DHH) is the prototype of H-1-antihistaminic drugs. It is a lipophilic drug, that easily crosses the blood-brain barrier when taken orally causing decrements in alertness and performance. Multiple applications of topical drug products are required. Thus, drug incorporation in nanocarriers would increase the skin penetration powers increasing the drug efficacy.MethodsChitosan-coated alginate (CCA) nanoparticles were prepared via polyelectrolyte complex technique adopting 2(3) full factorial designs. Three factors, namely, alginate concentration, drug-to-alginate ratio and CaCl2 volume, each in two levels were studied. The prepared formulae were evaluated utilizing entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and in vitro release. The characterization process was then followed by optimization.ResultsAt alginate conc. of 1%, drug to alginate ratio of 2:1 and CaCl2 volume of 4 mL, NP8 was chosen as a candidate formula. Histopathological examination on shaved rat dorsal skin disclosed the safety of NP8 with no signs of necrosis or even inflammation. The enhanced topical delivery of diphenhydramine hydrochloride enclosed in the developed nanoparticles was further proved by induction of allergic reaction using intradermal histamine injection. The results revealed the superior ability of NP8 to decrease the diameter of the formed wheal in comparison to the marketed DHH product.ConclusionThus, CCA nanoparticles are considered candidate nanocarriers for fortifying the topical antihistaminic activity of DHH.