Development of a novel niosomal formulation for Gabapentin

Document Type : Research/Original Article

Authors

1 Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran

2 Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran

4 Department of neurology, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Gabapentin is an anticonvulsant drug prescribed to treat partial seizures and neuropathic pain. Nisomes as a type of lipid based drug carriers can improve the pharmacokinetic properties of therapeutic agents. In this study, a niosomal formulation was developed for gabapentin, and then, the cytotoxicity effect of the best niosomal formulation was evaluated on normal cells and colon cancer cell lines.
Methods: A number of niosomal formulation were developed and their physicochemical properties were analysed. For G3 and G4 formulations, the release profile complies much better with Korsmeyer- Peppas model and suggesting the Fickian diffusion mechanism in gabapentin release. The effect of the optimized niosomal formulation of gabapentin on the (SW48) colon cancer cell line was assessed by MTT.
Results: The niosomal formulation of G3 showed 60% drug release in 48 hours, and the G4 formulation showed 52%. The cytotoxic effect of optimized formulation (G3) on colon cancer cell line (SW48) resulted in the IC50 of 45µg/ml (200µM) after 48 h, compared to 0.2 mg/mL (1.17 mM) for free gabapentin. As the results confirmed, niosomal formulation of gabapentin is more cytotoxic on colon cancer cell lines compared to pure gabapentin.
Conclusion: The best developed niosomal formulation of gabapentin exhibited good stablity on storage and had a slow and prolonged release of Gabapentin. This niosomal formulation of gabapentin showed cytotoxic effects on colon cancer cells, without significant toxic effect on normal fibroblast cells.

Keywords


  1. Wiffen PJ, McQuay HJ, Edwards J, Moore RA. Gabapentin for acute and chronic pain. Cochrane database of systematic reviews. 2005(3).
  2. Sills GJ. The mechanisms of action of gabapentin and pregabalin. Current opinion in pharmacology. 2006;6(1):108-13.
  3. Gidal BE, DeCerce J, Bockbrader HN, Gonzalez J, Kruger S, Pitterle ME, et al. Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy. Epilepsy research. 1998;31(2):91-9.
  4. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug metabolism and pharmacokinetics. 2012:1201060336-.
  5. Rimawi IB, Muqedi RH, Kanaze FI. Development of Gabapentin Expandable Gastroretentive Controlled Drug Delivery System. Scientific Reports. 2019;9(1):11675.
  6. Ma P-J, Gao G-J, Chang H-G, Shen F-Z, Hui L, Jin B-Z. Prolonged and floating drug delivery system of gabapentin for effective management of pain in spinal cord injury. International Journal of Pharmacology. 2016;12(4):435-9.
  7. Mbah CJ, Nnadi CO. Transdermal Delivery of Gabapentin: Effect of Cosolvent and Microemulsion on Permeation through the Rat Skin Pharmacology & Pharmacy. 2014;5:471-8.
  8. Suri SS, Fenniri H, Singh B. Nanotechnology-based drug delivery systems. Journal of occupational medicine and toxicology. 2007;2(1):16.
  9. Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Advanced drug delivery reviews. 2012;64(6):557-70.
  10. Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Advanced drug delivery reviews. 2013;65(6):822-32.
  11. Mei L, Zhang Z, Zhao L, Huang L, Yang X-L, Tang J, et al. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Advanced drug delivery reviews. 2013;65(6):880-90.
  12. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. Journal of controlled release. 2014;185:22-36.
  13. Abdelkader H, Alani AW, Alany RG. Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug delivery. 2014;21(2):87-100.
  14. Aggarwal D, Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. International journal of pharmaceutics. 2005;290(1-2):155-9.
  15. Abdelbary G, El-gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. Aaps Pharmscitech. 2008;9(3):740-7.
  16. Arunothayanun P, Turton JA, Uchegbu IF, Florence AT. Preparation and in vitro/in vivo evaluation of luteinizing hormone releasing hormone (LHRH)‐loaded polyhedral and spherical/tubular niosomes. Journal of pharmaceutical sciences. 1999;88(1):34-8.
  17. Gopinath D, Ravi D, Karwa R, Rao BR, Shashank A, Rambhau D. Pharmacokinetics of zidovudine following intravenous bolus administration of a novel niosome preparation devoid of cholesterol. Arzneimittelforschung. 2001;51(11):924-30.
  18. Ruckmani K, Sankar V, Sivakumar M. Tissue distribution, pharmacokinetics and stability studies of zidovudine delivered by niosomes and proniosomes. Journal of biomedical nanotechnology. 2010;6(1):43-51.
  19. Mullaicharam A, Murthy R. Lung accumulation of niosome-entrapped rifampicin following intravenous and intratracheal administration in the rat. Journal of Drug Delivery Science and Technology. 2004;14(2):99-104.
  20. Bini K, Akhilesh D, Prabhakara P, Kamath J. Development and characterization of non-ionic surfactant vesicles (niosomes) for oral delivery of lornoxicam. International Journal of Drug Development and Research. 2012;4(3):147-54.
  21. Ibrahim MM, Shehata TM. Tramadol HCl encapsulated niosomes for extended analgesic effect following oral administration. Journal of Drug Delivery Science and Technology. 2018;46:14-8.
  22. Sathali AAH, Rajalakshmi G. Evaluation of transdermal targeted niosomal drug delivery of terbinafine hydrochloride. International Journal of PharmTech Research. 2010;2(3):2081-9.
  23. Choi M, Maibach H. Liposomes and niosomes as topical drug delivery systems. Skin pharmacology and physiology. 2005;18(5):209-19.
  24. Muzzalupo R, Tavano L, Cassano R, Trombino S, Ferrarelli T, Picci N. A new approach for the evaluation of niosomes as effective transdermal drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics. 2011;79(1):28-35.
  25. Mahale N, Thakkar P, Mali R, Walunj D, Chaudhari S. Niosomes: novel sustained release nonionic stable vesicular systems—an overview. Advances in colloid and interface science. 2012;183:46-54.
  26. Azeem A, Anwer MK, Talegaonkar S. Niosomes in sustained and targeted drug delivery: some recent advances. Journal of drug targeting. 2009;17(9):671-89.
  27. Tarekegn A, Joseph NM, Palani S, Zacharia A, Ayenew Z. Niosomes in targeted drug delivery: some recent advances. IJPSR. 2010;1(9):1-8.
  28. Ghafelehbashi R, Akbarzadeh I, Yaraki MT, Lajevardi A, Fatemizadeh M, Saremi LH. Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes. International journal of pharmaceutics. 2019;569:118580.
  29. Junyaprasert VB, Singhsa P, Suksiriworapong J, Chantasart D. Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. International Journal of Pharmaceutics. 2012;423(2):303-11.
  30. Sadeghi S, Ehsani P, Cohan RA, Sardari S, Akbarzadeh I, Bakhshandeh H, et al. Design and Physicochemical Characterization of Lysozyme Loaded Niosomal Formulations as a New Controlled Delivery System. Pharmaceutical Chemistry Journal. 2020;53(10):921-30.
  31. Bharti N, Loona S, Khan M. Pro-niosomes: a recent advancement in nanotechnology as a drug carrier. International Journal of Pharmaceutical Sciences Review and Research. 2012;12:67-75.
  32. Taymouri S, Varshosaz J. Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes. Adv Biomed Res. 2016;5:48.
  33. Abdelkader H, Farghaly U, Moharram H. Effects of surfactant type and cholesterol level on niosomes physical properties and in vivo ocular performance using timolol maleate as a model drug. Journal of Pharmaceutical Investigation. 2014;44(5):329-37.
  34. Akbari V, Abedi D, Pardakhty A, Sadeghi-Aliabadi H. Release Studies on Ciprofloxacin Loaded Non-ionic Surfactant Vesicles. Avicenna J Med Biotechnol. 2015;7(2):69-75.
  35. Sadeghi S, Bakhshandeh H, Ahangari Cohan R, Peirovi A, Ehsani P, Norouzian D. Synergistic Anti-Staphylococcal Activity Of Niosomal Recombinant Lysostaphin-LL-37. Int J Nanomedicine. 2019;14:9777-92.
  36. Barani M, Mirzaei M, Torkzadeh-Mahani M, Nematollahi MH. Lawsone-loaded Niosome and its antitumor activity in MCF-7 breast Cancer cell line: a Nano-herbal treatment for Cancer. DARU Journal of Pharmaceutical Sciences. 2018;26(1):11-7.
  37. Hajizadeh MR, Maleki H, Barani M, Fahmidehkar MA, Mahmoodi M, Torkzadeh-Mahani M. In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents. Res Pharm Sci. 2019;14(5):448-58.
  38. Agarwal S, Mohamed MS, Raveendran S, Rochani AK, Maekawa T, Kumar DS. Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy. RSC advances. 2018;8(57):32621-36.
  39. Nasseri B. Effect of cholesterol and temperature on the elastic properties of niosomal membranes. International journal of pharmaceutics. 2005;300(1-2):95-101.
  40. Alemi A, Zavar Reza J, Haghiralsadat F, Zarei Jaliani H, Haghi Karamallah M, Hosseini SA, et al. Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. Journal of Nanobiotechnology. 2018;16(1):28.
  41. Manosroi A, Bauer KH. The Entrapment of A Human Insulin-Deae Dextran Complex in Different Compound Liposomes. Drug Development and Industrial Pharmacy. 1989;15(14-16):2531-46.
  42. Bruschi ML. Strategies to modify the drug release from pharmaceutical systems: Woodhead Publishing; 2015.
  43. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. International journal of pharmaceutics. 1983;15(1):25-35.
  44. Balasubramaniam A, Anil Kumar V, Sadasivan Pillai K. Formulation and in vivo evaluation of niosome-encapsulated daunorubicin hydrochloride. Drug developmentb and industrial pharmacy. 2002;28(10):1181-93.
  45. Seras-Cansell M, Ollivon M, Lesieur S. Generation of non-ionic monoalkyl amphiphile-cholesterol vesicles: evidence of membrane impermeability to octyl glucoside. STP pharma sciences. 1996;6(1):12-20.
  46. Pardakhty A, Moazeni E, Varshosaz J, Hajhashemi V, Rouholamini Najafabadi A. Pharmacokinetic study of niosome-loaded insulin in diabetic rats. Daru. 2011;19(6):404-11.
  47. Shokohi-pour Z, Chiniforoshan H, Momtazi-borojeni AA, Notash B. A novel Schiff base derived from the gabapentin drug and copper (II) complex: Synthesis, characterization, interaction with DNA/protein and cytotoxic activity. Journal of Photochemistry and Photobiology B: Biology. 2016;162:34-44.
  48. Lee C-Y, Lai H-Y, Chiu A, Chan S-H, Hsiao L-P, Lee S-T. The effects of antiepileptic drugs on the growth of glioblastoma cell lines. Journal of neuro-oncology. 2016;127(3):445-53.
  49. Dambach H, Hinkerohe D, Prochnow N, Stienen MN, Moinfar Z, Haase CG, et al. Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation. Epilepsia. 2014;55(1):184-92.
  50. Pavone A, Cardile V. An in vitro study of new antiepileptic drugs and astrocytes. Epilepsia. 2003;44:34-9.