DESIGN, CHARACTERIZATION AND BIOCOMPATIBILITY EVALUATION OF POLYMERIC NETWORKS AS CARRIERS FOR INDOMETHACIN MODIFIED RELEASE
Abstract
Pharmaceutical nanotechnology's progression expands drug versatility, utilizing carrier systems to efficiently deliver active ingredients to targeted tissues for controlled release within effective concentrations. Integrating nonsteroidal anti-inflammatory drugs (NSAIDs) into nano-systems holds potential for enhancing pharmacokinetic properties and diminishing adverse effects. Aim: Our study concentrated on formulating nanoparticles embedding indomethacin (IND), characterizing them, exploring drug release dynamics, and assessing their biocompatibility in rats. Materials and methods: IND was loaded within copolymeric networks comprising poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane) and poly(aspartic acid) (PAS) as a protective colloid, employing a dispersion polymerization approach. Fourier transform infrared spectroscopy (FT-IR) characterized the copolymeric matrices, and spectrophotometric analysis via dissolution method evaluated in vitro IND release. In vivo biocompatibility was gauged by monitoring hematological, biochemical, and immune parameters in rats. Results: Our developed nano-systems effectively loaded IND within polymeric matrices. The kinetics of IND release were influenced by copolymer composition, with lower comonomer concentrations extending release duration. The investigated copolymer networks incorporating IND did not elicit significant hematological, biochemical, or immune changes when administered to rats. Conclusions: the studied polymer samples exhibited promising in vivo biocompatibility, positioning them as potential candidates for IND modified-release systems with prospective biomedical applications.
References
2. Patil S, Chandrasekaran R. Biogenic nanoparticles: a comprehensive perspective in synthesis, charac-terization, application and its challenges. J Genet Eng Biotechnol 2020; 18(1): 67.
3. Birsan M, Dragan M, Stan CD, et al. A. Patient satisfaction regarding compounded pharmaceutical products and implications on pharmaceutical practice management. Farmacia 2021; 69(4): 806-12.
4. Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: a review of the implication of nanoparticles' physicochemical properties on responses in bio-logical systems. Polymers (Basel) 2023; 15(7): 1596.
5. Kulkarni D, Sherkar R, Shirsathe C et al. Biofabrication of nanoparticles: sources, synthesis, and biomedical applications. Front Bioeng Biotechnol 2023; 11: 1159193.
6. Shi S, Russell TP. Nanoparticle assembly at liquid-liquid interfaces: from the nanoscale to mesoscale. Adv Mater 2018; 30(44): e1800714.
7. Panchal NK, Prince Sabina E. Non-steroidal anti-inflammatory drugs (NSAIDs): A current insight into its molecular mechanism eliciting organ toxicities. Food Chem Toxicol 2023; 172: 113598.
8. Ghlichloo I, Gerriets V. Nonsteroidal anti-inflammatory drugs (NSAIDs) [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Accesed 10.06.2024.
9. Brusini R, Varna M, Couvreur P. Advanced nanomedicines for the treatment of inflammatory diseases. Adv Drug Deliv Rev 2020; 157: 161-178.
10. Abbasi R, Shineh G, Mobaraki M, Doughty S, Tayebi L. Structural parameters of nanoparticles af-fecting their toxicity for biomedical applications: a review. J Nanopart Res 2023; 25(3): 43.
11. Ravikumar C, Jagadeesh SS, Shridhar NB et al. An overview of NSAID loaded nanomaterials. J Pharm Innov 2023; 12(4): 43-58.
12. Pauna AR, Mititelu Tartau L, Bogdan M, et al. Synthesis, characterization and biocompatibility eval-uation of novel chitosan lipid micro-systems for modified release of diclofenac sodium. Biomedicines 2023; 11(2): 453.
13. Nita LE, Chiriac AP, Rusu AG et al. New self-healing hydrogels based on reversible physical interac-tions and their potential applications. Eur Polym J 2019; 118: 176-185.
14. Chiriac AP, Nita LE, Diaconu A et al. Hybrid gels by conjugation of hyaluronic acid with poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)undecane) copolymers. Int J Biol Macromol 2017; 98: 407-418.
15. Munjal A, Allam AE. Indomethacin. 2023 Jan 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. Accesed 15.06.2024.
16. Lichtenberger LM, Bhattarai D, Phan TM, Dial EJ, Uray K. Suppression of contractile activity in the small intestine by indomethacin and omeprazole. Am J Physiol Gastrointest Liver Physiol 2015; 308(9): G785-93.
17. Won KJ, Sanders KM, Ward SM. Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc Natl Acad Sci U S A 2005; 102(41): 14913-14918.
18. Rusu MC, Poalelungi CV, Vrapciu AD, Păduraru L, Didilescu AC, Stan CI. Anoctamin 1 positive esophageal interstitial Cajal cells in late stage human embryos. Anat Rec (Hoboken) 2014; 297(2): 301-307.
19. Fazio S, Bellavite P. Early multi-target treatment of mild-to-moderate covid-19, particularly in terms of non-steroidal anti-inflammatory drugs and indomethacin. BioMed 2023; 3(1): 177-194.
20. Perico N, Cortinovis M, Suter F, Remuzzi G. Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents. Lancet Infect Dis 2023; 23(1): e22-e33.
21. Fu Q, Lu H-D, Xie Y-F, et al. Salt formation of two BCS II drugs (indomethacin and naproxen) with (1R, 2R)-1,2-diphenylethylenediamine: Crystal structures, solubility and thermodynamics analysis. J Mol Struct 2019; 1185: 281-289.
22. Sohail R, Mathew M, Patel KK et al. Effects of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective NSAIDs on the gastrointestinal tract: a narrative review. Cureus 2023; 15(4): e37080.
23. Nita LE, Chiriac AP, Nistor MT, Tartau L. Indomethacin-loaded polymer nanocarriers based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane): preparation, in vitro and in vivo evaluation. J Biomed Mater Res B-Appl Biomater 2012; 100(4): 1121-1133.
24. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.
25. Dalmoro A, Bochicchio S, Nasibullin SF et al. Polymer-lipid hybrid nanoparticles as enhanced indo-methacin delivery systems. Eur J Pharm Sci 2018; 121: 16-28.
26. Mirgorodskaya AB, Koroleva MY, Kushnazarova RA et al. Microemulsions and nanoemulsions modified with cationic surfactants for improving the solubility and therapeutic efficacy of loaded drug indomethacin. Nanotechnology 2022; 33(15) / doi: 10.1088/1361-6528/ac467d.
27. Ishkhanyan H, Rhys NH, Barlow DJ, Lawrence MJ, Lorenz CD. Impact of drug aggregation on the structural and dynamic properties of Triton X-100 micelles. Nanoscale 2022; 14(14): 5392-5403.
28. Nihala N, Mathan S, Rajalekshmi VR, Bineesha KB. Development of formulation and in vitro evalua-tion of sterically stabilized (stealth) liposomes containing selected anti-arthritic drug. J Pharm Sci Res 2019; 11: 3526-3535.
29. Carvalho A, Lopes I, Gonçalves O, Bárbara E, Real Oliveira MECD, Lúcio M. Polymeric versus lipid nanoparticles: comparative study of nanoparticulate systems as indomethacin carriers. J Appl Sol Chem Model 2015; 4: 1-15.
30. Liu H, Bolleddula J, Nichols A, Tang L, Zhao Z, Prakash C. Metabolism of bioconjugate therapeutics: Why, when, and how? Drug Metab Rev 2020; 52: 66-124.
31. Shan RM, Eldridge DS, Palombo EA, Harding IH. Stability mechanisms for microwave-produced solid lipid nanoparticles. Colloids Surf a Physicochem Eng Asp 2022; 643: 128774.
32. Dupeyrón D, Kawakami M, Ferreira AM et al. Design of indomethacin-loaded nanoparticles: effect of polymer matrix and surfactant. Int J Nanomedicine 2013; 8: 3467-3477.
33. Colombo M, Minussi C, Orthmann S, Staufenbiel S, Bodmeier R. Preparation of amorphous indo-methacin nanoparticles by aqueous wet bead milling and in situ measurement of their increased satu-ration solubility. Eur J Pharm Biopharm 2018; 125: 159-168.
34. Babu VS, Yachendhra PG, Raju KNVS, Rao KA. Preparation and characterization of indomethacin-loaded chitosan nanoparticles. IAJPS 2022; 9(9): 85-94.
Additional Files
Published
Issue
Section
License
COPYRIGHT
Once an article is accepted for publication, MSJ requests a transfer of copyrights for published articles.
COPYRIGHT TRANSFER FORM FOR
REVISTA MEDICO-CHIRURGICALĂ A SOCIETĂȚII DE MEDICI ȘI NATURALIȘTI DIN IAȘI /
THE MEDICAL-SURGICAL JOURNAL OF THE SOCIETY OF PHYSICIANS AND NATURALISTS FROM IASI
We, the undersigned authors of the manuscript entitled
_____________________________________________________________________________________
_____________________________________________________________________________________
warrant that this manuscript, which is submitted for publication in the REVISTA MEDICO-CHIRURGICALĂ, has not been published and it is not under consideration for publication in another journal.
- we give the consent for publication in the REVISTA MEDICO-CHIRURGICALĂ, in printed and electronic format and we transfer unconditioned and complete the copyright of this manuscript to the REVISTA MEDICO-CHIRURGICALĂ, in the event of its acceptance.
- the manuscript does not break the intellectual property rights of any other person.
- we have read the submitted version of the manuscript and we are fully responsible for the content.
Names and signatures of authors / copyright owners (the following sequence is the authorship of the article):
- ______________________________/_________________________
- ______________________________/_________________________
- ______________________________/_________________________
N.B. All the authors must sign this form