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. 2023 May 9:11:1173883.
doi: 10.3389/fbioe.2023.1173883. eCollection 2023.

Development and evaluation of pH sensitive semi-interpenetrating networks: assessing the impact of itaconic acid and aloe vera on network swelling and cetirizine release

Nyla Ajaz  1   2 , Munnaza Bukhsh  3 , Yousaf Kamal  4 , Fauzia Rehman  1   2 , Muhammad Irfan  1 , Syed Haroon Khalid  1 , Sajid Asghar  1 , Waleed Y Rizg  5   6 , Sahar M Bukhary  7 , Khaled M Hosny  6 , Mohammed Alissa  8 , Awaji Y Safhi  9 , Fahad Y Sabei  9 , Ikram Ullah Khan  1
Affiliations

Development and evaluation of pH sensitive semi-interpenetrating networks: assessing the impact of itaconic acid and aloe vera on network swelling and cetirizine release

Nyla Ajaz et al. Front Bioeng Biotechnol. .

Abstract

Hydrogels are crosslinked three-dimensional networks, and their properties can be easily tuned to target the various segments of the gastrointestinal tract (GIT). Cetirizine HCl (CTZ HCl) is an antihistaminic drug, which when given orally can upset the stomach. Moreover, this molecule has shown maximum absorption in the intestine. To address these issues, we developed a pH-responsive semi-interpenetrating polymer network (semi-IPN) for the delivery of CTZ HCl to the lower part of the GIT. Initially, 10 different formulations of itaconic acid-grafted-poly (acrylamide)/aloe vera [IA-g-poly (AAm)/aloe vera] semi-IPN were developed by varying the concentration of IA and aloe vera using the free radical polymerization technique. Based on swelling and sol-gel analysis, formulation F5 containing 0.3%w/w aloe vera and 6%w/w IA was chosen as the optimum formulation. The solid-state characterization of the optimized formulation (F5) revealed a successful incorporation of CTZ HCl in semi-IPN without any drug-destabilizing interaction. The in vitro drug release from F5 showed limited release in acidic media followed by a controlled release in the intestinal environment for over 72 h. Furthermore, during the in vivo evaluation, formulation F5 did not affect the hematological parameters, kidney, and liver functions. Clinical observations did not reveal any signs of illness in rabbits treated with hydrogels. Histopathological images of vital organs of treated animals showed normal cellular architecture. Thus, the results suggest a non-toxic nature and overall potential of the developed formulation as a targeted drug carrier.

Keywords: aloe vera; itaconic acid; pH sensitive; semi-interpenetrating network; sustainability of natural resources.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The graphical presentation of the initial ingredients, possible structure, and loading of CTZ HCl in IA-g-poly (AAm)/aloe vera semi-IPN hydrogel.
FIGURE 2
FIGURE 2
The optical images of dry and swollen hydrogels at pH 1.2 and 7.4.
FIGURE 3
FIGURE 3
The effect of increasing concentrations of aloe vera (A) and IA (B) on the swelling ratio (g/g) of semi-IPN hydrogels.
FIGURE 4
FIGURE 4
FTIR spectra of pure drug, blank, and drug-loaded semi-IPN hydrogels (F5).
FIGURE 5
FIGURE 5
The SEM micrograph of (A) CTZ HCl, (B) blank, and (C) drug-loaded semi-IPN hydrogels (F5).
FIGURE 6
FIGURE 6
DSC thermograms of blank, F5, and blank semi-IPN hydrogels.
FIGURE 7
FIGURE 7
TGA thermograms of pure drug, blank, and CTZ HCl-loaded semi-IPN hydrogels.
FIGURE 8
FIGURE 8
XRD of pure drug, blank, and CTZ HCl-loaded hydrogel (F5).
FIGURE 9
FIGURE 9
In vitro CTZ HCl release from semi-IPN hydrogel (F5). The release curve shows the Korsmeyer Peppas model on the first 60% release (Shown by the red line).
FIGURE 10
FIGURE 10
Histopathological images of vital organs. All images were acquired at 40x on a Tinocular microscope, Accu-Scope 3,001 fitted with a five-megapixel camera. Here, the alphabets represent, G: glomerulus, B: bronchiole, A: alveolus, CV: central vein, and C: cardiac muscles.
See this image and copyright information in PMC

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Grants and funding

The Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, Saudi Arabia, funded this project under grant no (RG-2-166-43).