Hybrid crosslinked hydrogel-based drug delivery systems can deliver therapeutically beneficial drug release effects through controlled release on a temporal and spatial scale. Due to their tuneable physicochemical properties and the ability to prevent drug degradation, these systems facilitate different physicochemical interactions that control drug release. This research aims to synthesize a potent pH-sensitive crosslinked chitosan/polyvinylpyrrolidone hydrogel using different ratios of both the polymers and varying the glutaraldehyde crosslinking agent amount by the solution casting technique for controlled amoxicillin-release properties to mitigate gastrointestinal tract bacterial infection. The effect of polymer ratios and glutaraldehyde amount is investigated by the developing porosity, gel fraction, and extent of swelling in simulated physiological fluids of pH 1.2, 6.8, and 7.4 and in vitro biodegradation at pH 7.4. Interaction between the polymers with the formation of crosslinked structures, good stability, amorphous phase nature, and honeycomb-like structures of the hydrogels is revealed by Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. Based on these properties, a chitosan/polyvinylpyrrolidone hydrogel (ratio of 60:40) crosslinked with 600 μL glutaraldehyde in 8 g of the polymers displaying adequate swelling in acidic to basic pH and in vitro biodegradation at pH 7.4 is chosen for the in situ loading of 200 mg of the drug amoxicillin. The cumulative drug release in simulated physiological fluids and the drug release kinetics using different models show that the best-fit Korsmeyer-Peppas model suggests amoxicillin release from the matrix follows diffusion and swelling-controlled time-dependent non-Fickian transport related to hydrogel erosion. This composition displays excellent antimicrobial activity against Streptococcus pyogenes and Escherichia coli.
GibsonDJWardMGRentschC, et al. Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease. Aliment Pharmacol Ther2020; 51: 612–628.
2.
MalikNSAhmadMAlqahtaniMS, et al. β-Cyclodextrin chitosan-based hydrogels with tunable pH-responsive properties for controlled release of acyclovir: design, characterization, safety, and pharmacokinetic evaluation. Drug Deliv2021; 28: 1093–1108.
3.
JafariHHassanpourMAkbariA, et al. Characterization of pH-sensitive chitosan/hydroxypropyl methylcellulose composite nanoparticles for delivery of melatonin in cancer therapy. Mater Lett2021; 282: 128818.
4.
DasSSBharadwajPBilalM, et al. Stimuli-responsive polymeric nanocarriers for drug delivery, imaging, and theragnosis. Polymers2020; 12: 1397.
5.
OsornoLBrandleyAMaldonadoD, et al. Review of contemporary self-assembled systems for the controlled delivery of therapeutics in medicine. Nanomater2021; 11: 278.
OnaciuAMunteanuRAMoldovanAI, et al. Hydrogels based drug delivery synthesis, characterization and administration. Pharmaceutics2019; 11: 432.
8.
Bustamante-TorresMRomero-FierroDArcentales-VeraB, et al. Hydrogels classification according to the physical or chemical interactions and as stimuli-sensitive materials. Gels2021; 7: 182.
9.
WangS.Synthesis and characterisation of stimuli-responsive amino acid-based polymeric materials for drug delivery. PhD Thesis, Imperial College Press, London, 2018.
10.
GullNKhanSMButtOM, et al. Inflammation targeted chitosan-based hydrogel for controlled release of diclofenac sodium. Int J Biol Macromol2020; 162: 175–187.
11.
ChatterjeeSHuiPCSiuWS, et al. Influence of pH-responsive compounds synthesized from chitosan and hyaluronic acid on dual-responsive (pH/temperature) hydrogel drug delivery systems of Cortex Moutan. Int J Biol Macromol2021; 168: 163–174.
12.
AdhaNErvinaIAgusnarH.The effectiveness of metronidazole gel based chitosan inhibits the growth of bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum (In vitro). Int J Appl Dent Sci2017; 3: 30–37.
13.
PervaizFSaleemMAshamesA, et al. Development and ex-vivo skin permeation studies of finasteride–poly(lactic acid-co-glycolic acid) and minoxidil–chitosan nanoparticulate systems. J Bioact Compat Polym2020; 35: 77–91.
14.
SethiAAhmadMHumaT, et al. Evaluation of low molecular weight cross linked chitosan nanoparticles, to enhance the bioavailability of 5-flourouracil. Dose Response2021; 19(2): 15593258211025353.
15.
ArchanaDSinghBKDuttaJ, et al. In vivo evaluation of chitosan-PVP-titanium dioxide nanocomposite as wound dressing material. Carbohydr Polym2013; 95: 530–539.
16.
PereiraAKDSReisDTBarbosaKM, et al. Antibacterial effects and ibuprofen release potential using chitosan microspheres loaded with silver nanoparticles. Carbohydr Res2020; 488: 107891.
17.
Saeedi GarakaniSDavachiSMBagherZ, et al. Fabrication of chitosan/polyvinylpyrrolidone hydrogel scaffolds containing PLGA microparticles loaded with dexamethasone for biomedical applications. Int J Biol Macromol2020; 164: 356–370.
18.
GullNKhanSMKhalidS, et al. Designing of biocompatible and biodegradable chitosan based crosslinked hydrogel for in vitro release of encapsulated povidone-iodine: a clinical translation. Int J Biol Macromol2020; 164: 4370–4380.
19.
GullNKhanSMZahid ButtMT, et al. In vitro study of chitosan-based multi-responsive hydrogels as drug release vehicles: a preclinical study. RSC Adv2019; 9: 31078–31091.
20.
RasoolAAtaSIslamA.Stimuli responsive biopolymer (chitosan) based blend hydrogels for wound healing application. Carbohydr Polym2019; 203: 423–429.
21.
QasimSSBNogueriaLPFawzyAS, et al. The effect of crosslinking efficiency of drug-loaded novel freeze gelated chitosan templates for periodontal tissue regeneration. AAPS PharmSciTech2020; 21: 173.
22.
IslamNDmourITahaMO.Degradability of chitosan micro/nanoparticles for pulmonary drug delivery. Heliyon2019; 5: e01684.
23.
BallantyneBJordanSL.Toxicological, medical, and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures. J Appl Toxicol2001; 21: 131–151.
24.
TakigawaTEndoY.Effects of glutaraldehyde exposure on human health. J Occup Health2006; 48: 75–87.
25.
HuttnerABielickiJClementsMN, et al. Oral amoxicillin and amoxicillin-clavulanic acid: properties, indications and usage. Clin Microbiol Infect2020; 26: 871–879.
26.
MartínezJSBGonzálezASLópezMC, et al. Electrochemical degradation of amoxicillin in acidic aqueous medium using tioo(2)-based electrodes modified by oxides of transition metals.-based electrodes modified by oxides of transition metals. Environ Sci Pollut Res2022; 29: 42130–42145.
27.
RisbudMVHardikarAABhatSV, et al. PH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. J Control Release2000; 68: 23–30.
28.
MarquesMRCLoebenbergRAlmukainziM.Simulated biological fluids with possible application in dissolution testing. Diss Technol2011; 18: 15–28.
29.
AvellaAMinchevaRRaquezJM, et al. Substantial effect of water on radical melt crosslinking and rheological properties of poly(ε-caprolactone). Polymers2021; 13: 491.
30.
RadePPGiramPSShitoleAA, et al. Physicochemical and in vitro antibacterial evaluation of metronidazole loaded eudragit S-100 nanofibrous mats for the intestinal drug delivery. adv Fiber mater2022; 4: 76–88.
31.
GullNKhanSMButtMTZ, et al. Hybrid cross-linked hydrogels as a technology platform forinvitrorelease of cephradine. Polym Adv Technol2019; 30: 2414–2424.
32.
KhurmaJRRohindraDRNandAV.Swelling and thermal characteristics of genipin crosslinked chitosan and poly(vinyl pyrrolidone) hydrogels. Polym Bull2005; 54: 195–204.
33.
El AchabyMEssamlaliYEl MiriN, et al. Graphene oxide reinforced chitosan/polyvinylpyrrolidone polymer bio-nanocomposites. J Appl Polym Sci2014; 131: 41042.
34.
NematollahiEPourmadadiMYazdianF, et al. Synthesis and characterization of chitosan/polyvinylpyrrolidone coated nanoporous γ-alumina as a pH-sensitive carrier for controlled release of quercetin. Int J Biol Macromol2021; 183: 600–613.
35.
BudiantoEAmaliaA.Swelling behavior and mechanical properties of chitosan-poly(N-vinyl-pyrrolidone) hydrogels. J Polym Eng2020; 40: 551–560.
36.
AfrianiKSutanti BudikaniaT.Synthesis and characterization of hydrogel of Chitosan-poly (N-vinyl-2-pirrolidone) (PVP)- alginate for ibuprofen release. J Pure Appl Chem Res2020; 9: 201–211.
BeppuMMVieiraRSAimoliCG, et al. Crosslinking of chitosan membranes using glutaraldehyde: effect on ion permeability and water absorption. J Membr Sci2007; 301: 126–130.
39.
AkakuruOUIsiukuBO. Chitosan hydrogels and their glutaraldehyde-crosslinked counterparts as potential drug release and tissue engineering systems-synthesis, characterization, swelling kinetics and mechanism. J Phys Chem Biophys2017; 7: 256.
40.
MogilevskayaELAkopovaTAZelenetskiiAN, et al. The crystal structure of chitin and chitosan. Polym Sci Ser A2006; 48: 116–123.
41.
KocyigitAYilmazMAydoganS, et al. The performance of chitosan layer in Au/n-Si sandwich structures as a barrier modifier. Polym Test2020; 89: 106546.
42.
LewandowskaK.Miscibility and interactions in chitosan acetate/poly(N-vinylpyrrolidone) blends. Thermochim Acta2011; 517: 90–97.
43.
BajpaiSKShahFFBajpaiM, et al. Dynamic release of amoxicillin from orally dissolving film (ODF) composed of casein and sodium alginate. J Drug Res Dev2017; 3: 2470–1009.
44.
ArchanaDSinghBKDuttaJ, et al. Chitosan-PVP-nano silver oxide wound dressing: in vitro and in vivo evaluation. Int J Biol Macromol2015; 73: 49–57.
45.
PoonguzhaliRBashaSKKumariVS.Synthesis and characterization of chitosan-PVP-nanocellulose composites for in-vitro wound dressing application. Int J Biol Macromol2017; 105: 111–120.
46.
MondalRKDubeyKAKumarJ, et al. Carbon nanotube functionalization and radiation induced enhancements in the sensitivity of standalone chemiresistors for sensing volatile organic compounds. ACS appl Nano mater2018; 1: 5470–5482.
47.
Najaf OshaniBDavachiSMHejaziI, et al. Enhanced compatibility of starch with poly(lactic acid) and poly(ε-caprolactone) by incorporation of POSS nanoparticles: study on thermal properties. Int J Biol Macromol2019; 141: 578–584.
48.
XiongWZhangQYinF, et al. Auricularia auricular polysaccharide-low molecular weight chitosan polyelectrolyte complex nanoparticles: preparation and characterization. Asian J Pharm Sci2016; 11: 439–448.
49.
DuceacIAVerestiucLDimitriuCD, et al. Design and preparation of new multifunctional hydrogels based on chitosan/acrylic polymers for drug delivery and wound dressing applications. Polymers2020; 12: 1473.
50.
Fei LiuXLin GuanYZhi YangD, et al. Antibacterial action of chitosan and carboxymethylated chitosan. J Appl Polym Sci2001; 79: 1324–1335.
51.
ParkPJJeJYByunHG, et al. Antimicrobial activity of hetero-chitosans and their oligosaccharides with different molecular weights. J Microbiol Biotechnol2004; 14: 317–323.
52.
SudarshanNRHooverDGKnorrD.Antibacterial action of chitosan. Food Biotechnol1992; 6: 257–272.
