https://onlinelibrary.wiley.com/doi/pdf/10.1002/app.50376

Synthetic hydrogels: Synthesis, novel trends, and applications

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.

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Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer

Synthetic polymers, biopolymers, and their nanocomposites are being studied, and some of them are already used in different medical areas. Among the synthetic ones that can be mentioned are polyolefins, fluorinated polymers, polyesters, silicones, and others. Biopolymers such as polysaccharides (chitosan, hyaluronic acid, starch, cellulose, alginates) and proteins (silk, fibroin) have also become widely used and investigated for applications in medicine. Besides synthetic polymers and biopolymers, their nanocomposites, which are hybrids formed by a macromolecular matrix and a nanofiller (mineral or organic), have attracted great attention in the last decades in medicine and in other fields due to their outstanding properties. This review covers studies done recently using the polymers, biopolymers, nanocomposites, polymer micelles, nanomicelles, polymer hydrogels, nanogels, polymersomes, and liposomes used in medicine as drugs or drug carriers for cancer therapy and underlines their responses to internal and external stimuli able to make them more active and efficient. They are able to replace conventional cancer drug carriers, with better results.

Polymers and Polymer Nanocomposites for Cancer Therapy

Current study is focused to enhance the solubility of poorly soluble drug olanzapine (OLZ) by nanogels drug delivery system, as improved solubility is one of the most important applications of nanosystems. Poor solubility is a major issue, and 40% of marketed and about 75% of new active pharmaceutical ingredients are poorly water soluble which significantly affect the bioavailability and therapeutic effects of these drugs. In this study, nanogels, a promising system for solubility enhancement, were developed by free-radical polymerization technique. Different formulations were synthesized in which poloxamer-407 was cross-linked with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with the help of cross-linker methylene bisacrylamide (MBA). The chemically cross-linked nanogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermos gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta size, swelling, sol-gel analysis, drug loading, solubility, and in vitro drug release studies. In order to determine the biocompatibility and cytotoxicity of nanogels to biological system, toxicity study on rabbits was also carried out. It was confirmed that the developed nanogels was thermally stable, safe, effective, and compatible to biological system, and the solubility of olanzapine (OLZ) was enhanced up to 38 folds as compared with reference product.

Poloxamer-407-Co-Poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Nanogels for Solubility Enhancement of Olanzapine: Synthesis, Characterization, and Toxicity Evaluation

We have developed a dual-sensitive composite hydrogel network from guar gum grafted polyacrylamidoglycolic acid (graft polymer) using sodium borohydride, which induces cross-linking and growth of silver nuclei by reduction reaction through a fast and easy route. The cross-linked graft polymer (GGAA) and its silver nanocomposite (GGAA@SNC) hydrogels have been successfully utilized to explore sustained release of 5-fluorouracil (5-FU), an anticancer drug, and antibacterial activity was evaluated. The composite hydrogels exhibit sol-gel behavior due to pH and temperature effect. To identify the functional interactions of pure guar gum (GG), graft polymer, 5-FU loaded GGAA and GGAA@SNC hydrogels, the synthesized materials are characterized by FTIR, DSC, and XRD analysis. In addition, the growth of silver nanoparticles (SNPs), its size, and stability in the hydrogel network were verified by UV-vis spectra, FE-TEM, and TGA-DTA analysis. Additionally, the structural morphology and porosity of polymer structures were observed by FE-SEM analysis. The different polymer network parameters (Mc, χ, 휉 and ϕ) and diffusion constant (D) were calculated by using swelling data and evaluated to assess the drug release profile. The diffusion exponents (n) were determined by studying 5-FU release behavior of the composite hydrogels in phosphate buffer solution (pH = 1.2 & 7.4); in vitro release data indicated that, maximum 5-FU release was significantly achieved in pH 7.4 rather than pH 1.2. The GGAA@SNC hydrogels showed excellent antibacterial activity towards Bacillus subtilis and Salmonella ebony using zone of inhibition test. A versatile strategy has been developed to prepare GGAA@SNC hydrogels to enhance 5-FU release over 16 h for its effective anticancer drug release applications.

Guar gum graft polymer-based silver nanocomposite hydrogels: synthesis, characterization and its biomedical applications

Chemical cross-linking of monomers methacrylic acid (MAA) and itaconic acid (IA) through ethylene glycol dimethacrylate (EGDMA) was carried out for synthesizing robust hydrogel system for oral administration and tuned for targeted release of 5-fluorouracil (5-FU) and leucovorin calcium (LV) at colonic site.
 Aqueous-based free radical polymerization method was optimized first, and then a series of batches were prepared. Various in vitro tests were performed to probe the characteristics of synthesized hydrogels such as the presence of functional groups, surface morphology, crystalline/amorphous properties and thermal stability which confirms the cross-linking and stability of hydrogels. Swelling, drug loading and drug release evaluations were carried out at two different pH levels of 1.2 and pH 7.4. pH responsiveness was observed in synthesized hydrogels. Co-polymeric hydrogels exhibited higher swelling and release at higher pH 7.4 as compared to lower pH 1.2. Moreover, an increased trend in swelling and drug release was observed for formulations with higher content of IA. Co-polymeric hydrogels were biocompatible and non-toxic to biological system as investigated by acute oral toxicity study on rabbits.

Synthesis of hydrogels for combinatorial delivery of 5-fluorouracil and leucovorin calcium in colon cancer: optimization, in vitro characterization and its toxicological evaluation

Synthesis, optimization, and evaluation of polyvinyl alcohol‐based hydrogels as controlled combinatorial drug delivery system for colon cancer

Current study aimed to develop and evaluate interpenetrating polymer network (IPN) nanogels for transdermal delivery of ondansetron (OND) using combination of natural and synthetic polymers. Owing ...

Chitosan-PVA-co-poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Hybrid IPN-Nanogels for Transdermal Delivery of Ondansetron; Synthesis, Characterization and Toxicological Evaluation

Aousaf Ahmad

Papers

Synthesis of hydrogels for combinatorial delivery of 5-fluorouracil and leucovorin calcium in colon cancer: optimization, in vitro characterization and its toxicological evaluation

Synthesis, optimization, and evaluation of polyvinyl alcohol‐based hydrogels as controlled combinatorial drug delivery system for colon cancer

Chitosan-PVA-co-poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Hybrid IPN-Nanogels for Transdermal Delivery of Ondansetron; Synthesis, Characterization and Toxicological Evaluation