Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

Department of Basic Medical Sciences Shifa College of Pharmaceutical Sciences Shifa Tameer e Millat University Islamabad Pakistan

Department of Pharmacognosy College of Pharmacy King Saud University Riyadh Saudi Arabia

Department of Pharmacy Faculty of Medical and Health Sciences University of Poonch Rawalakot Azad Kashmir Pakistan

Department of Social and Clinical Pharmacy Faculty of Pharmacy in Hradec Králové Charles University Prague Prague Czech Republic

Department of Surgery College of Medicine King Saud University Riyadh Kingdom of Saudi Arabia

Faculty of Health Sciences Equator University of Science and Technology Masaka Uganda

Faculty of Pharmacy The University of Lahore Lahore Pakistan

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Soares GA, de Castro AD, Cury BS, Evangelista RC. Blends of cross-linked high amylose starch/pectin loaded with diclofenac. Carbohydrate Polymers. 2013;91(1):135–42. doi: 10.1016/j.carbpol.2012.08.014 PubMed DOI

Malaterre V, Metz H, Ogorka J, Gurny R, Loggia N, Mäder K. Benchtop-magnetic resonance imaging (BT-MRI) characterization of push–pull osmotic controlled release systems. Journal of Controlled Release. 2009;133(1):31–6. doi: 10.1016/j.jconrel.2008.09.007 PubMed DOI

Tao SL, Desai TA. Microfabricated drug delivery systems: from particles to pores. Advanced drug delivery reviews. 2003;55(3):315–28. doi: 10.1016/s0169-409x(02)00227-2 PubMed DOI

Freiberg S, Zhu X. Polymer microspheres for controlled drug release. International journal of pharmaceutics. 2004;282(1):1–18. doi: 10.1016/j.ijpharm.2004.04.013 PubMed DOI

Van Tomme SR, Storm G, Hennink WE. In situ gelling hydrogels for pharmaceutical and biomedical applications. International journal of pharmaceutics. 2008;355(1):1–18. doi: 10.1016/j.ijpharm.2008.01.057 PubMed DOI

Ahmed EM. Hydrogel: preparation, characterization, and applications. Journal of advanced research. 2015;6:105–21. PubMed PMC

Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug discovery today. 2002;7(10):569–79. doi: 10.1016/s1359-6446(02)02255-9 PubMed DOI

Soares PA, de Seixas JRC, Albuquerque PB, Santos GR, Mourão PA, Barros W, et al.. Development and characterization of a new hydrogel based on galactomannan and κ-carrageenan. Carbohydrate polymers. 2015;134:673–9. PubMed

Chen I-C, Su C-Y, Chen P-Y, Hoang TC, Tsou Y-S, Fang H-W. Investigation and Characterization of Factors Affecting Rheological Properties of Poloxamer-Based Thermo-Sensitive Hydrogel. Polymers. 2022;14(24):5353. doi: 10.3390/polym14245353 PubMed DOI PMC

Peppas N, Bures P, Leobandung W, Ichikawa H. Hydrogels in pharmaceutical formulations. European journal of pharmaceutics and biopharmaceutics. 2000;50(1):27–46. doi: 10.1016/s0939-6411(00)00090-4 PubMed DOI

Sohail M, Ahmad M, Minhas MU, Liaqat A, Munir A, Khalid I. Synthesis and characterization of graft PVA composites for controlled delivery of valsartan. Lat Am J Pharm. 2014;33(8):1237–44.

Ganji F, Vasheghani-Farahani E. Hydrogels in controlled drug delivery systems. Iran Polym J. 2009;18(1):63–88.

Anwar H, Ahmad M, Minhas MU, Rehmani S. Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization. Carbohydrate Polymers. 2017;166:183–94. doi: 10.1016/j.carbpol.2017.02.080 PubMed DOI

Elliott JE, Macdonald M, Nie J, Bowman CN. Structure and swelling of poly (acrylic acid) hydrogels: effect of pH, ionic strength, and dilution on the crosslinked polymer structure. Polymer. 2004;45(5):1503–10.

Escobar-Chávez JJ, López-Cervantes M, Naik A, Kalia Y, Quintanar-Guerrero D, Ganem-Quintanar A. Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. Journal of Pharmacy & Pharmaceutical Sciences. 2006;9(3):339–58. PubMed

Chun KW, Lee JB, Kim SH, Park TG. Controlled release of plasmid DNA from photo-cross-linked pluronic hydrogels. Biomaterials. 2005;26(16):3319–26. doi: 10.1016/j.biomaterials.2004.07.055 PubMed DOI

Karavasili C, Komnenou A, Katsamenis OL, Charalampidou G, Kofidou E, Andreadis D, et al.. Self-Assembling Peptide Nanofiber Hydrogels for Controlled Ocular Delivery of Timolol Maleate. ACS Biomaterials Science & Engineering. 2017;3(12):3386–94. PubMed

Design Lall D., characterization and evaluation of hydrogel based Timolol formulation for effective treatment of Glaucoma. Asian Journal of Pharmacy and Pharmacology. 2020;6(4):231–8.

Anwar F, Mahmood E, Sharif S, Shah R, Jamgochian M, Ouellette S, et al.. Topical Application of 0.5% Timolol Maleate Hydrogel for the Treatment of Superficial Infantile Hemangiomas. Journal of drugs in dermatology: JDD. 2023;22(6):594–8. doi: 10.36849/JDD.7054 PubMed DOI

Yuan Xiong X, Chiu Tam K, Huat Gan L. Synthesis and thermally responsive properties of novel pluronic F87/polycaprolactone (PCL) block copolymers with short PCL blocks. Journal of applied polymer science. 2006;100(5):4163–72.

Bromberg L. Polyether-modified poly (acrylic acid): synthesis and applications. Industrial & engineering chemistry research. 1998;37(11):4267–74.

Rafique N, Ahmad M, Minhas MU, Badshah SF, Malik NS, Khan KU. Designing gelatin-based swellable hydrogels system for controlled delivery of salbutamol sulphate: Characterization and toxicity evaluation. Polym Bull. 2022;79(7):4535–61.

Liaqat H, Badshah SF, Minhas MU, Barkat K, Khan SA, Hussain MD, et al.. pH-Sensitive Hydrogels Fabricated with Hyaluronic Acid as a Polymer for Site-Specific Delivery of Mesalamine. ACS Omega. 2024. doi: 10.1021/acsomega.4c03240 PubMed DOI PMC

Badshah SF, Minhas MU, Khan KU, Barkat K, Abdullah O, Munir A, et al.. Structural and in-vitro characterization of highly swellable β-cyclodextrin polymeric nanogels fabricated by free radical polymerization for solubility enhancement of rosuvastatin. Particulate Science and Technology. 2023;41(8):1131–45.

Popa L, Ghica MV, Dinu-Pirvu C. Hydrogels: Smart materials for biomedical applications: BoD–Books on Demand; 2019.

Badshah SF, Akhtar N, Minhas MU, Khan KU, Khan S, Abdullah O, et al.. Porous and highly responsive cross-linked β-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption. Life Sciences. 2021;267:118931. PubMed

Akkari AC, Papini JZB, Garcia GK, Franco MKD, Cavalcanti LP, Gasperini A, et al.. Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation. Materials Science and Engineering: C. 2016;68:299–307. doi: 10.1016/j.msec.2016.05.088 PubMed DOI

Masteikova R, Chalupova Z, Sklubalova Z. Stimuli-sensitive hydrogels in controlled and sustained drug delivery. Medicina. 2003;39(2):19–24. PubMed

Lo Y-L, Hsu C-Y, Lin H-R. pH-and thermo-sensitive pluronic/poly (acrylic acid) in situ hydrogels for sustained release of an anticancer drug. Journal of Drug Targeting. 2013;21(1):54–66. doi: 10.3109/1061186X.2012.725406 PubMed DOI

Pascoal A, da Silva P, Pinheiro MC. Drug dissolution profiles from polymeric matrices: Data versus numerical solution of the diffusion problem and kinetic models. International Communications in Heat and Mass Transfer. 2015;61:118–27.

Ali M, Horikawa S, Venkatesh S, Saha J, Hong JW, Byrne ME. Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow. Journal of Controlled Release. 2007;124(3):154–62. doi: 10.1016/j.jconrel.2007.09.006 PubMed DOI

Grindel JM, Jaworski T, Emanuele RM, Culbreth P. Pharmacokinetics of a novel surface‐active agent, purified poloxamer 188, in rat, rabbit, dog and man. Biopharmaceutics & drug disposition. 2002;23(3):87–103. doi: 10.1002/bdd.297 PubMed DOI

Moharram M, Allam MA. Study of the interaction of poly (acrylic acid) and poly (acrylic acid‐poly acrylamide) complex with bone powders and hydroxyapatite by using TGA and DSC. Journal of applied polymer science. 2007;105(6):3220–7.

Alexandridis P, Holzwarth JF. Differential scanning calorimetry investigation of the effect of salts on aqueous solution properties of an amphiphilic block copolymer (Poloxamer). Langmuir. 1997;13(23):6074–82.

Che Ani N, Jamari SS, Wan Yaacob WSN, editors. Effect of cross-linker concentration on the synthesis and swelling behaviour of superabsorbent polymers (SAP) using graft polymerization techniques. Key Engineering Materials; 2017: Trans Tech Publ.

Fulgêncio GdO Viana FAB, Ribeiro RR Yoshida MI, Faraco AG Cunha-Júnior AdS. New mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate: in vivo evaluation. Journal of Ocular Pharmacology and therapeutics. 2012;28(4):350–8. doi: 10.1089/jop.2011.0174 PubMed DOI

Newa M, Bhandari KH, Li DX, Kwon T-H, Kim JA, Yoo BK, et al.. Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. International journal of pharmaceutics. 2007;343(1–2):228–37. doi: 10.1016/j.ijpharm.2007.05.031 PubMed DOI

Nanaki S, Eleftheriou RM, Barmpalexis P, Kostoglou M, Karavas E, Bikiaris D. Evaluation of dissolution enhancement of aprepitant drug in ternary pharmaceutical solid dispersions with Soluplus® and Poloxamer 188 prepared by melt mixing. Sci. 2019;1(2):48.

Mehta P, Al-Kinani AA, Arshad MS, Chang M-W, Alany RG, Ahmad Z. Development and characterisation of electrospun timolol maleate-loaded polymeric contact lens coatings containing various permeation enhancers. International journal of pharmaceutics. 2017;532(1):408–20. doi: 10.1016/j.ijpharm.2017.09.029 PubMed DOI

Passerini N, Albertini B, González-Rodríguez ML, Cavallari C, Rodriguez L. Preparation and characterisation of ibuprofen–poloxamer 188 granules obtained by melt granulation. European Journal of Pharmaceutical Sciences. 2002;15(1):71–8. doi: 10.1016/s0928-0987(01)00210-x PubMed DOI

Roy H, Nayak BS, Nandi S. Poloxamer based Urapidil Loaded Chitosan Microparticle in Approach to Improve the Mechanical Strength by Tensile Strength and Entrapment Determination. Current Drug Therapy. 2022;17(1):56–70.

Shah AV, Serajuddin AT. Development of solid self-emulsifying drug delivery system (SEDDS) I: use of poloxamer 188 as both solidifying and emulsifying agent for lipids. Pharmaceutical research. 2012;29:2817–32. doi: 10.1007/s11095-012-0704-x PubMed DOI

Aytimur A, Koçyiğit S, Uslu İ. Synthesis and characterization of poly (vinyl alcohol)/poly (vinyl pyrrolidone)-iodine nanofibers with poloxamer 188 and chitosan. Polymer-Plastics Technology and Engineering. 2013;52(7):661–6.

Roy H, Nayak BS, Nandi S. In Silico; Factorial Screening and Optimization of Chitosan Based Gel for Urapidil Loaded Microparticle using Reduced Factorial Design. Combinatorial Chemistry & High Throughput Screening. 2020;23(10):1049–63. PubMed

Magami SM, Williams RL. Gelation studies on acrylic acid‐based hydrogels via in situ photo‐crosslinking and rheology. Journal of Applied Polymer Science. 2018;135(38):46691.

Bukhari SMH, Khan S, Rehanullah M, Ranjha NM. Synthesis and characterization of chemically cross-linked acrylic acid/gelatin hydrogels: effect of pH and composition on swelling and drug release. International Journal of Polymer Science. 2015;2015.

Samanta HS, Ray SK. Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide. Carbohydrate polymers. 2014;99:666–78. doi: 10.1016/j.carbpol.2013.09.004 PubMed DOI

Devi DR, Sandhya P, Hari BV. Poloxamer: a novel functional molecule for drug delivery and gene therapy. Journal of Pharmaceutical Sciences and Research. 2013;5(8):159.

Nesrinne S, Djamel A. Synthesis, characterization and rheological behavior of pH sensitive poly (acrylamide-co-acrylic acid) hydrogels. Arabian Journal of Chemistry. 2017;10(4):539–47.

Barkat K, Ahmad M, Minhas MU, Khalid I. Oxaliplatin‐loaded crosslinked polymeric network of chondroitin sulfate‐co‐poly (methacrylic acid) for colorectal cancer: its toxicological evaluation. Journal of Applied Polymer Science. 2017;134(38):45312.

Kulkarni SP, Amin PD. Stability indicating HPTLC determination of timolol maleate as bulk drug and in pharmaceutical preparations. Journal of pharmaceutical and biomedical analysis. 2000;23(6):983–7. doi: 10.1016/s0731-7085(00)00389-7 PubMed DOI

Hiratani H, Alvarez-Lorenzo C. The nature of backbone monomers determines the performance of imprinted soft contact lenses as timolol drug delivery systems. Biomaterials. 2004;25(6):1105–13. doi: 10.1016/s0142-9612(03)00622-7 PubMed DOI

Law T, Whateley T, Florence A. Some chemically modified poloxamer hydrogels: preparation, morphology and swelling properties. International journal of pharmaceutics. 1984;21(3):277–87.

Stanojević M, Krušić MK, Filipović J, Parojčić J, Stupar M. An investigation into the influence of hydrogel composition on swelling behavior and drug release from poly (acrylamide-co-itaconic acid) hydrogels in various media. Drug delivery. 2006;13(1):1–7. doi: 10.1080/10717540500313034 PubMed DOI

Korsmeyer RW, Von Meerwall E, Peppas NA. Solute and penetrant diffusion in swellable polymers. II. Verification of theoretical models. Journal of Polymer Science Part B: Polymer Physics. 1986;24(2):409–34.