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

Abstract

Objective

The aim of the present study was to formulate chitosan-coated alginate nanoparticles containing the drug diphenhydramine hydrochloride (DHH).

Significance

Diphenhydramine hydrochloride (DHH) is the prototype of H₁-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.

Methods

Chitosan-coated alginate (CCA) nanoparticles were prepared via polyelectrolyte complex technique adopting 2³ 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.

Results

At 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.

Conclusion

Thus, CCA nanoparticles are considered candidate nanocarriers for fortifying the topical antihistaminic activity of DHH.