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. 2021 Jun 11;14(6):557.
doi: 10.3390/ph14060557.

Optimization of Novel Naproxen-Loaded Chitosan/Carrageenan Nanocarrier-Based Gel for Topical Delivery: Ex Vivo, Histopathological, and In Vivo Evaluation

Sobia Noreen  1 , Fahad Pervaiz  1 , Akram Ashames  2   3 , Manal Buabeid  3   4 , Khairi Fahelelbom  5 , Hina Shoukat  1 , Irsah Maqbool  1 , Ghulam Murtaza  6
Affiliations

Optimization of Novel Naproxen-Loaded Chitosan/Carrageenan Nanocarrier-Based Gel for Topical Delivery: Ex Vivo, Histopathological, and In Vivo Evaluation

Sobia Noreen et al. Pharmaceuticals (Basel). .

Abstract

Naproxen (NAP) is commonly used for pain, inflammation, and stiffness associated with arthritis. However, systemic administration is linked with several gastrointestinal tract (GIT) side effects. The present work aims to prepare and evaluate NAP nanoparticulate shells of chitosan (CS) and carrageenan (CRG) loaded into a Carbopol 940 (Ca-940) gel system with unique features of sustained drug delivery as well as improved permeation through a topical route. Moreover, this study aims to evaluate its ex vivo, histopathological, and in vivo anti-inflammatory activity in albino Wistar rats. The percentage of ex vivo drug permeation patterns in the optimized formulation (No) was higher (88.66%) than the control gel (36.195%). Oral toxicity studies of developed nanoparticles in albino rabbits showed that the NAP-loaded CS/CRG are non-toxic and, upon histopathological evaluation, no sign of incompatibility was observed compared to the control group. A In Vivo study showed that the optimized gel formulation (No) was more effective than the control gel (Nc) in treating arthritis-associated inflammation. The sustained permeation and the absence of skin irritation make this novel NAP nanoparticle-loaded gel based on CS/CRG a suitable drug delivery system for topical application and has the potential for improved patient compliance and reduced GIT-related side effects in arthritis.

Keywords: Ca-940 gel; anti-inflammatory; carrageenan; chitosan; nanocarriers; naproxen; polyelectrolyte complexation; toxicity study.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a,c) SEM microphotographs of N11 and optimized No naproxen-loaded CS/CRG nanoparticle formulation liquid dispersion; (b,d) lyophilized; (e) and particle size and PDI of N15 formulation.
Figure 2
Figure 2
(a) FTIR spectra of naproxen, (b) chitosan, (c) carrageenan, (d) physical mixture, and (e) optimized formulation.
Figure 3
Figure 3
XRD spectra of naproxen, carrageenan, chitosan, physical mixture, and optimized formulation.
Figure 4
Figure 4
(a) Influence of polymer concentration and drug concentration on entrapment efficiency and (b) influence of polymer concentration and stirring speed on entrapment efficiency.
Figure 5
Figure 5
(a) Influence of polymer concentration and drug concentration on particle size and (b) influence of drug concentration and speed on particle size.
Figure 6
Figure 6
(a) Drug permeation percentage of formulation with 0.05% of carrageenan; (b) with 0.06% carrageenan; (c) with 0.07% carrageenan; (d) optimized formulation (No) containing Carbopol 940 gel and control formulation (Nc) containing Carbopol 940 gel through FT rat skin.
Figure 7
Figure 7
(a) Influence of polymer concentration and stirring speed on drug permeation percentage. (b) Effect of drug concentration and stirring speed on drug permeation percentage.
Figure 8
Figure 8
Histopathological examination of different organs of Group I (control group) and Group II (treatment group) of rabbits.
Figure 9
Figure 9
(a) Photograph of control animal rat paw; (b) photograph of formalin-induced rat paw; (c) photograph of NAP-gel-treated rat paw; (d) photograph of control-gel-treated rat paw.
Figure 10
Figure 10
Histopathological study of rat paw tissue; (A) control paw tissue showed normal epidermis, deep dermis, and subcutaneous tissues; (B) (a) group treated with formalin alone showed marked hyperkeratosis of skin with epithelial proliferation. (b) Under dermis loosens and is edematous. (c) Deep dermis and subcutaneous tissues show moderate inflammatory cell infiltration. (d) edema, and proliferation of collagenous tissue. (C) (c) FIE + control-gel-treated group shows deep dermis and subcutaneous tissues with mild inflammatory cell infiltration, (d) edema, and proliferation of collagenous tissue. (D) FIE + NAP-gel-treated group showed a marked reduction in the injury to paw tissue. Most of the histological changes were minimized and found negligible as compared to the group treated with formalin alone. (FIE = formalin-induced edema).
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