Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63–75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen–Crowell’s kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.

[1]  Z. Hussain,et al.  Development and Evaluation of Sodium Alginate/Carbopol 934P-Co-Poly (Methacrylate) Hydrogels for Localized Drug Delivery , 2023, Polymers.

[2]  M. Zaman,et al.  Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine , 2023, Gels.

[3]  M. Zaman,et al.  Novel Black Seed Polysaccharide Extract-g-Poly (Acrylate) pH-Responsive Hydrogel Nanocomposites for Safe Oral Insulin Delivery: Development, In Vitro, In Vivo and Toxicological Evaluation , 2022, Pharmaceutics.

[4]  E. Taha,et al.  Development and Optimization of Tamarind Gum-β-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir , 2022, Pharmaceuticals.

[5]  Cihangir Boztepe,et al.  Modeling the Effect of Physical Crosslinking Degree of pH and Temperature Responsive Poly(NIPAAm-Co-VSA)/Alginate IPN Hydrogels on Drug Release Behavior , 2022, SSRN Electronic Journal.

[6]  M. Chorilli,et al.  Solid dipersions included in poloxamer hydrogels have favorable rheological properties for topical application and enhance the in vivo antiinflammatory effect of ursolic acid , 2022, Journal of Drug Delivery Science and Technology.

[7]  W. Aman,et al.  Development of Statistically Optimized Chemically Cross-Linked Hydrogel for the Sustained-Release Delivery of Favipiravir , 2022, Polymers.

[8]  Mohammed S. Alqahtani,et al.  pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation , 2022, Pharmaceutics.

[9]  Lina Zheng,et al.  Development of Gelatin Methacryloyl Hydrogel loaded ZnS Nanoparticles Patches for In vivo wound healing care, In vitro drug release and free radical scavenging evaluations , 2022, Journal of Drug Delivery Science and Technology.

[10]  Jaemin Kim,et al.  Novel acyclovir-loaded film-forming gel with enhanced mechanical properties and skin permeability , 2022, Journal of Drug Delivery Science and Technology.

[11]  S. Bashir,et al.  Fenugreek seed mucilage grafted poly methacrylate pH-responsive hydrogel: A promising tool to enhance the oral bioavailability of methotrexate. , 2022, International journal of biological macromolecules.

[12]  Vivek Dave,et al.  Biomedical applications of hydrogels in drug delivery system: An update , 2021, Journal of Drug Delivery Science and Technology.

[13]  A. Mahmood,et al.  Chitosan/Agarose‐g‐poly (methacrylate) pH responsive polymeric blend: A dais for controlled delivery of Capecitabine , 2021 .

[14]  M. Al-Tabakha,et al.  Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir , 2021, Pharmaceuticals.

[15]  Huaping Tan,et al.  A facile injectable carbon dot/oxidative polysaccharide hydrogel with potent self-healing and high antibacterial activity. , 2021, Carbohydrate polymers.

[16]  Bilal Ahmad Lodhi,et al.  Basil (Ocimum basilicum L.) seeds engender a smart material for intelligent drug delivery: On-Off switching and real-time swelling, in vivo transit detection, and mechanistic studies , 2020 .

[17]  I. Hussain,et al.  A smart drug delivery system based on Artemisia vulgaris hydrogel: Design, on-off switching, and real-time swelling, transit detection, and mechanistic studies , 2020 .

[18]  F. Aouada,et al.  On the preparation and physicochemical properties of pH-responsive hydrogel nanocomposite based on poly(acid methacrylic)/laponite RDS , 2020, Materials Today Communications.

[19]  S. Vaezifar,et al.  Preparation and characterization of sodium alginate/polyvinyl alcohol hydrogel containing drug-loaded chitosan nanoparticles as a drug delivery system , 2020, Journal of Drug Delivery Science and Technology.

[20]  Gautam Sen,et al.  Gum ghatti based hydrogel: Microwave synthesis, characterization, 5-Fluorouracil encapsulation and 'in vitro' drug release evaluation. , 2019, Carbohydrate polymers.

[21]  Hasan Zuhudi Abdullah,et al.  Electrophoretic deposition of chitosan-based composite coatings for biomedical applications: A review , 2019, Progress in Materials Science.

[22]  E. Çakal,et al.  The Swelling Behaviors of poly(2-acrylamido-2-methyl-1-propane sulfonic acid co-1-vinyl-2-pyrrolidone) Hydrogels , 2018 .

[23]  S. Bashir,et al.  Quince seed hydrogel (glucuronoxylan): Evaluation of stimuli responsive sustained release oral drug delivery system and biomedical properties , 2018, Journal of Drug Delivery Science and Technology.

[24]  P. Ma,et al.  Injectable antibacterial conductive hydrogels with dual response to an electric field and pH for localized "smart" drug release. , 2018, Acta biomaterialia.

[25]  Mahmood Ahmad,et al.  Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir , 2017, PloS one.

[26]  S. Bashir,et al.  A superporous and superabsorbent glucuronoxylan hydrogel from quince (Cydonia oblanga): Stimuli responsive swelling, on-off switching and drug release. , 2017, International journal of biological macromolecules.

[27]  M. Minhas,et al.  β-CD based hydrogel microparticulate system to improve the solubility of acyclovir: Optimization through in-vitro, in-vivo and toxicological evaluation , 2016 .

[28]  N. M. Ranjha,et al.  The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium , 2016, Designed monomers and polymers.

[29]  Wei Zhou,et al.  Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing. , 2016, International journal of biological macromolecules.

[30]  M. F. Akhtar,et al.  Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH–sensitive acrylic acid–polyvinyl alcohol hydrogel , 2015, DARU Journal of Pharmaceutical Sciences.

[31]  M. Sohail,et al.  Controlled delivery of valsartan by cross-linked polymeric matrices: Synthesis, in vitro and in vivo evaluation. , 2015, International journal of pharmaceutics.

[32]  V. Khutoryanskiy,et al.  Biomedical applications of hydrogels: A review of patents and commercial products , 2015 .

[33]  Xian Jun Loh,et al.  Advances in hydrogel delivery systems for tissue regeneration. , 2014, Materials science & engineering. C, Materials for biological applications.

[34]  Ullrich Scherf,et al.  Conjugated polymer-assisted dispersion of single-wall carbon nanotubes: the power of polymer wrapping. , 2014, Accounts of chemical research.

[35]  S. Ray,et al.  Controlled release of tinidazole and theophylline from chitosan based composite hydrogels. , 2014, Carbohydrate polymers.

[36]  Jing Zhu,et al.  Click synthesis by Diels-Alder reaction and characterisation of hydroxypropyl methylcellulose-based hydrogels , 2014, Chemical Papers.

[37]  M. Sohail,et al.  Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; a potential graft-polymeric carrier for oral delivery of 5-fluorouracil , 2013, DARU Journal of Pharmaceutical Sciences.

[38]  Yuquan Wei,et al.  Synthesis and characterization of poly(methoxyl ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate) pH-sensitive hydrogel for delivery of dexamethasone. , 2010, International journal of pharmaceutics.

[39]  Miqin Zhang,et al.  Chitosan-based hydrogels for controlled, localized drug delivery. , 2010, Advanced drug delivery reviews.

[40]  S. Erramilli,et al.  Rheology of gastric mucin exhibits a pH-dependent sol-gel transition. , 2007, Biomacromolecules.

[41]  J. Filipović,et al.  Copolymer hydrogels based on N-isopropylacrylamide and itaconic acid , 2006 .

[42]  Lin Li,et al.  Release of theophylline from polymer blend hydrogels. , 2005, International journal of pharmaceutics.

[43]  N A Peppas,et al.  Mathematical modeling of controlled drug delivery. , 2001, Advanced drug delivery reviews.

[44]  M. Vignon,et al.  Isolation, 1H and 13C NMR studies of (4-O-methyl-d-glucurono)-d-xylans from luffa fruit fibres, jute bast fibres and mucilage of quince tree seeds , 1998 .

[45]  Nicholas A. Peppas,et al.  A simple equation for description of solute release II. Fickian and anomalous release from swellable devices , 1987 .

[46]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[47]  J. Wagner Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. , 1969, Journal of pharmaceutical sciences.

[48]  T. Higuchi MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[49]  A. W. Hixson,et al.  Dependence of Reaction Velocity upon surface and Agitation , 1931 .

[50]  M. Minhas,et al.  Synthesis and Characterization of Poly(hydroxyethyl methacrylate-co-methacrylic acid) Cross Linked Polymeric Network for the Delivery of Analgesic Agent , 2015 .

[51]  Xin-feng Cheng,et al.  Oxidation- and thermo-responsive poly(N-isopropylacrylamide-co-2-hydroxyethyl acrylate) hydrogels cross-linked via diselenides for controlled drug delivery , 2015 .

[52]  Z. Zafar,et al.  Effect of Cross Linker Concentration on Swelling Kinetics of a Synthesized Ternary Co-Polymer System , 2012 .

[53]  Sac-fry Stages,et al.  OECD GUIDELINE FOR TESTING OF CHEMICALS , 2002 .

[54]  G. Phillips,et al.  Interaction of Univalent and Divalent Cations with Carrageenans in Aqueous Solution , 1977 .