Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels.

Munir Ahmad Khan,Mohamed Kamel,Asif Nawaz,Md Habibur Rahman,Mohamed M Abdel-Daim,Roua S Baty,Muhammad Akhlaq,Abul Kalam Azad,Attalla F El-Kott,Pijush Paul,Simona G Bungau,Muhammad Safdar,Md Kamal Hossain

doi:10.3390/gels8010047

Abstract

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation’s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug’s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

Highlights

The worldwide prevalence of colonic disease is increasing with over one hundred thousand colorectal cancer patients newly diagnosed every year [1]
The mechanism of polymerization of acrylic acid and acrylamide in the presence of glutaraldehyde (GA) cross-linker was adapted from Wang et al and partially modified the synthesis reaction mechanism shown in Scheme 1
The cross-linker glutaraldehyde (5) was added after polymerization finished in order to avoid the crosslinking reaction of Poly(acrylic acid-co-acrylamide) (4) during polymerization

Summary

Introduction

The worldwide prevalence of colonic disease is increasing with over one hundred thousand colorectal cancer patients newly diagnosed every year [1]. Colon-targeted drug delivery systems for the local treatment of colonic diseases are urgently sought [3]. It is important to take into consideration the area neighboring the disease site(s) as well as the colon physiology, since the GI tract experiences constant changes in motility, fluid composition, pH from the small to the large intestine, and enzymatic activity [5]. Numerous formulation strategies have been investigated to develop colonic drug delivery (i.e., enzyme-sensitive systems, magnetically triggered systems, and pH-responsive systems) [6]. Several types of pH-responsive hydrogels have been investigated for site specific drug delivery owing to significant pH variations in the GI tract, where the drug release characteristics change with the variations in the medium pH because of relaxation of the chain [11]

Objectives

Results

Conclusion