Effect of Pluronic F127 Concentration on Gelling Temperature and other Parameters of Lomustine Mucoadhesive In-Situ Gel

Authors

  • Maryam H. Alaayedi Department of Pharmaceutics, College of Pharmacy, University of Mustansiriyah, Baghdad, Iraq
  • Nidhal Khazaal Maraie Department of Pharmaceutics, College of Pharmacy, Al-Farahidi University, Baghdad, Iraq https://orcid.org/0000-0001-5628-1479

DOI:

https://doi.org/10.31351/vol33iss3pp63-71

Keywords:

Pluronic F127, brain tumor, lomustine, in-situ gel.

Abstract

Pluronic F127 is one of the widely used thermoreversible gelling agent, and used in sol-to-gel transformation. It has been used to localize drug delivery such as nose-to-brain delivery which allows the direct targeting of drug molecules bypassing the systemic effect and BBB (Blood Brain Barrier). The anticancer drug lomustine had poor oral bioavailability in addition to its serious side effect, therefore, developing more effective drug delivery with direct targeting towards the brain through intra-nasal administration applying nanoemulsion-based-in situ gel technology is a promising alternative. The work involved formulation of lomustine as in situ gel using Pluronic F127 and study the effect of the polymer on solution to gel transition temperature, gelation behaviour, spreadability, mucoadhesive force, residence time and residence drug percentage, as well as in vitro drug release. The results showed acceptable pH and high drug content, beside increased Pluronic percentage (from 15 to 20%) led to reduced gelation temperature from 33°C to 27°C and spreadability, improved gelling properties from + to +++, increasing mucoadhesive force from 4965.33 to 9866.30 dyne/cm2 as well as prolonged residence time from 30 to 66 min and in vitro drug release where was 120 min for 100% drug release from F1 that contained 15% of the polymer to 210 min for F3 with 20% polymer. Therefore, modifying the Pluronic F127 percent in the in situ formulas could optimize the required formula for targeting the anticancer to treat brain cancer via nose-to-brain delivery.

References

Bashir, R., M. Maqbool, I. Ara, and M. Zehravi, An In sight into Novel Drug Delivery System: In Situ Gels. CELLMED, 2021 ;11(1) :6.1-6.7.

Padmasri B, Nagaraju R, Prasanth D. A comprehensive review on in situ gels. International Journal of Applied Pharmaceutics. 2020;12(6):24-33.

El-Shenawy AA, Mahmoud RA, Mahmoud EA, Mohamed MS. Intranasal In Situ Gel of Apixaban-Loaded Nanoethosomes: Preparation, Optimization, and In Vivo Evaluation. AAPS PharmSciTech. 2021; 22 (4) :147.

Marie NK. Preparation, evaluation and dissolution behaviors of water soluble drug loaded PLGA microspheres. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2007;4(1):23-31.

Bayanati M, Khosroshahi AG, Alvandi M, Mahboobian MM. Fabrication of a thermosensitive in situ gel nanoemulsion for nose to brain delivery of temozolomide. Journal of Nanomaterials. 2021;2021:1-11.

Unal S, Tekeli M, Dogan O, Aktas Y. Thermosensitive Pluronic® F127-Based in situ gel formulation containing nanoparticles for the sustained delivery of paclitaxel. Medicine Science. 2023;2023(12): 224-30.

Yu J, Qiu H, Yin S, Wang H, Li Y. Polymeric drug delivery system based on pluronics for cancer treatment. Molecules. 2021;26(12):3610.

Abdulla NA, Balata GF, El-Ghamry HA, Gomaa E. Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement. Saudi Pharmaceutical Journal. 2021;29(12):1466-85.

Pragatheeswaran AM, Chen SB. Effect of chain length of PEO on the gelation and micellization of the pluronic F127 copolymer aqueous system. Langmuir. 2013;29(31):9694-701.

CHEN W-z, ZHAO H-f, YANG L-h. Outline for British Pharmacopoeia 2013. Chinese Journal of Pharmaceutical Analysis. 2013;33(4):709-15.

Gustafson DL, Page RL. Cancer chemotherapy. Withrow and MacEwen’s small animal clinical oncology. 2013:157-79.

Hussein, N.R., H.K. Omer, A.M. Elhissi, and W. Ahmed, Advances in nasal drug delivery systems, in Advances in medical and surgical engineering. 2020, Elsevier. p. 279-311.

Haumann R, Videira JC, Kaspers GJ, van Vuurden DG, Hulleman E. Overview of current drug delivery methods across the blood–brain barrier for the treatment of primary brain tumors. CNS drugs. 2020;34(11):1121-31.

Alaayedi MH, Maraie NK. Lomustine’s nanoemulsion as nose-to-brain drug delivery system for CNS tumor treatment. Saudi Pharmaceutical Journal. 2023;31(8):101692.

Pandit NK, Kisaka J. Loss of gelation ability of Pluronic® F127 in the presence of some salts. International Journal of Pharmaceutics. 1996;145(1-2):129-36.

Venkatesh D, Kamlesh L, Kumar P. Development and evaluation of chitosan based thermosensitive in situ gels of pilocarpine. Int J Pharm Pharmaceut Sci. 2013; 5:164-9.

Suhagiya, K., C.H. Borkhataria, S. Gohil, R.A. Manek, K.A. Patel, N.K. Patel, and D.V. Patel, Development of Mucoadhesive In-Situ Nasal Gel Formulation for Enhanced Bioavailability and Efficacy of Rizatriptan in Migraine Treatment. Results in Chemistry, 2023:101010.

Maraie NK, Almajidi YQ. Effect of different mucoadhesive polymers on release of ondansetron HCl from intranasal mucoadhesive in situ gel. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2017;17(2):76-85.

Al-Shammary FJ. Analytical profile of lomustine. Analytical Profiles of Drug Substances. 19: Elsevier; 1990. p. 315-40.

Ansel HC. Pharmaceutical calculations: Lippincott Williams & Wilkins; 2012.

Galgatte UC, Kumbhar AB, Chaudhari PD. Development of in situ gel for nasal delivery: design, optimization, in vitro and in vivo evaluation. Drug delivery. 2014;21(1):62-73.

Vipul V, Basu B. Formulation and characterization of novel floating in-situ gelling system for controlled delivery of ramipril. International Journal of Drug Delivery. 2013;5(1):43.

Alkufi HK, Kassab HJ. Formulation and evaluation of sustained release sumatriptan mucoadhesive intranasal in-situ gel. Iraqi J Pharm Sci. 2019;28(2):95-104.

Nair AB, Chaudhary S, Shah H, Jacob S, Mewada V, Shinu P, et al. Intranasal delivery of darunavir-loaded mucoadhesive in situ gel: Experimental design, in vitro evaluation, and pharmacokinetic studies. Gels. 2022;8(6):342.

Singh RM, Kumar A, Pathak K. Thermally triggered mucoadhesive in situ gel of loratadine: β-cyclodextrin complex for nasal delivery. AAPS PharmSciTech. 2013; 14:412-24.

Nerkar PP, Gattani S. In vivo, in vitro evaluation of linseed mucilage based buccal mucoadhesive microspheres of venlafaxine. Drug Delivery. 2011;18(2):111-21.

Ravi P, Aditya N, Patil S, Cherian L. Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization. Drug delivery. 2015;22(7):903-10.

Zaki NM, Awad GA, Mortada ND, Abd ElHady SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. European journal of pharmaceutical sciences. 2007;32(4-5):296-307.

Patil S, Dhage A, Patil S, Patil S. Formulation and evaluation of nasal in situ gel for Alzheimer disease. Int Res J Pharma Bio Sci. 2015;2(2):41-58.

De A, Chakraborty S, Mukherjee A, Chattopadhyay J, Ghatak S. Design and optimization of nasal in situ gel of ondansetron using factorial design. IJRPC. 2013;3(48):659-73.

Maraie NK, Almajidi YQ. Application of nanoemulsion technology for preparation and evaluation of intranasal mucoadhesive nano-in-situ gel for ondansetron HCl. Journal of Global Pharma Technology. 2018;10(03):431-42.

Nair AB, Chaudhary S, Jacob S, Patel D, Shinu P, Shah H, et al. Intranasal Administration of Dolutegravir-Loaded Nanoemulsion-Based In Situ Gel for Enhanced Bioavailability and Direct Brain Targeting. Gels. 2023;9(2):130.

Mahajan HS, Jadhao VD, Chandankar SM. Pullulan and Pluronic F-127 based in situ gel system for intranasal delivery: Development, in vitro and in vivo evaluation. Journal of Bioactive and Compatible Polymers. 2022;37(48):406-18.

Lehr C-M. Lectin-mediated drug delivery: The second generation of bioadhesives. Journal of Controlled Release. 2000;65(1-2):19-29.

Jagdale S, Shewale N, Kuchekar BS. Optimization of thermoreversible in situ nasal gel of timolol maleate. Scientifica. 2016;2016.

Bonaccorso A, Gigliobianco MR, Pellitteri R, Santonocito D, Carbone C, Di Martino P, et al. Optimization of curcumin nanocrystals as promising strategy for nose-to-brain delivery application. Pharmaceutics. 2020;12(48):476.

Pires PC, Paiva-Santos AC, Veiga F. Antipsychotics - Loaded Nanometric Emulsions for Brain Delivery. Pharmaceutics. 2022; 14(10):2174.

Katona G, Sipos B, Budai-Szűcs M, Balogh GT, Veszelka S, Gróf I, et al. Development of in situ gelling meloxicam-human serum albumin nanoparticle formulation for nose-to-brain application. Pharmaceutics. 2021;13(48):646.

Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. The Open Drug Delivery Journal. 2008;2(1).

García-Couce J, Tomás M, Fuentes G, Que I, Almirall A, Cruz LJ. Chitosan/Pluronic F127 thermosensitive hydrogel as an injectable dexamethasone delivery carrier. Gels. 2022;8(1):44.

Londhe V, Krishnan S, editors. Formulation, Evaluation, and Pharmacodynamic Investigation of Ziprasidone-b-cyclodextrin In-Situ Nasal Gel. Proceedings; 2020: MDPI.

Alabdly, A. and H.J. Kassab, Formulation Variables Effect on Gelation Temperature of Nefopam Hydrochloride intranasal in Situ Gel. Iraqi Journal of Pharmaceutical Sciences, 2022;31(Suppl.):32-44.

Ways TMM, Lau WM, Khutoryanskiy VV. Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers. 2018;10(48):267.

Upadhayay P, Kumar M, Pathak K. Norfloxacin loaded pH triggered nanoparticulate in-situ gel for extraocular bacterial infections: optimization, ocular irritancy and corneal toxicity. Iranian Journal of Pharmaceutical Research: IJPR. 2016;15(1):3.

Nagai N, Isaka T, Deguchi S, Minami M, Yamaguchi M, Otake H, et al. In situ gelling systems using pluronic F127 enhance corneal permeability of indomethacin nanocrystals. International journal of molecular sciences. 2020;21(19):7083.

Mikušová V, Mikuš P. Advances in chitosan-based nanoparticles for drug delivery. International Journal of Molecular Sciences. 2021;22(17):9652.

Sheshala R, Wai NZ, Said ID, Ashraf K, Lim SM, Ramasamy K, et al. Poloxamer and Chitosan-Based In Situ Gels Loaded with Orthosiphon Stamineus Extracts Containing Rosmarinic Acid for the Treatment of Ocular Infections. Turk J Pharm Sci. 2022; 19(6): 671–680.

Downloads

Published

2024-09-15

How to Cite

1.
Maryam H. Alaayedi, Nidhal Khazaal Maraie. Effect of Pluronic F127 Concentration on Gelling Temperature and other Parameters of Lomustine Mucoadhesive In-Situ Gel. IJPS [Internet]. 2024 Sep. 15 [cited 2024 Sep. 27];33(3):63-71. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/2669