Development of a thermo-sensitive in situ nasal gel with nanoparticles of poly(lactic-co-glycolic) acid copolymer containing favipiravir
- Authors: Derkach V.S.1, Gordienko M.G.1
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Affiliations:
- D.I. Mendeleyev University of Chemical Technology
- Issue: Vol 28, No 12 (2025)
- Pages: 28-35
- Section: Pharmaceutical chemistry
- URL: https://ogarev-online.ru/1560-9596/article/view/362633
- DOI: https://doi.org/10.29296/25877313-2025-12-04
- ID: 362633
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Abstract
Introduction. Favipiravir is a selective inhibitor of viral RNA polymerase with a broad spectrum of antiviral activity; however, its low aqueous solubility results in reduced oral bioavailability. Therefore, the development of new delivery systems, such as thermosensitive nasal in situ gels, is necessary.
The purpose of the work. To develop and characterize thermosensitive in situ gels based on P407 and P188 for intranasal delivery.
Material and methods. Favipiravir-loaded PLGA nanoparticles were prepared using nanoprecipitation. Particle diameter was deter- mined using dynamic light scattering (DLS) at 25 °C. Thermosensitive gels were prepared using the cold method with varying P407 concentrations and varying the P407/P188 ratio. Rheological properties were measured using a SmartPave 102 rheometer at 10–40 °C and a heating rate of 0.05 °C/sec. In vitro release studies were conducted using a DHC-6T transdermal diffusion tester in phosphate buffer, pH 6.4, at 37 °C, with samples analyzed at six time points using UV spectrophotometry.
Results. The average diameter of favipiravir-loaded PLGA nanoparticles was 168.14±3.49 nm, a suitable size for intranasal delivery via the nose-to-brain mechanism. In situ temperature-sensitive gel studies revealed that as the P407 concentration increased from 18 to 25% by weight, the Tsol-gel decreased from 29.04±0.63 °C to 21.84±0.19 °C. The addition of P188 at an 8/2 ratio (P407/P188) significantly increased the T in the sol-gel by 6.64–8.38 °C compared to systems without P188. The favipiravir release profile from the API suspension was characterized by rapid release (46% in 5 min, 72% in 10 min); from PLGA nanoparticles, by delayed release (17– 29% in 5–10 min, 94% in 120 min); and from the in situ gel with nanoparticles, by the most prolonged release (3–9% in 5–10 min, 65% in 120 min).
Conclusion. An intranasal delivery system consisting of PLGA nanoparticles loaded with favipiravir in a thermosensitive in situ gel ma- trix based on P407 and P188 was developed. A dual release control mechanism (polymer degradation and delayed diffusion from the gel matrix) provides a pronounced prolonged effect.
About the authors
V. S. Derkach
D.I. Mendeleyev University of Chemical Technology
Author for correspondence.
Email: derkach.v.s@muctr.ru
ORCID iD: 0009-0007-3508-2586
SPIN-code: 1967-2548
Junior Research Scientist, Laboratory for the Development of Innovative Nasal and Inhalation Drugs
Russian Federation, 9, building 1, Miusskaya Ploshchad, Moscow, 125047M. G. Gordienko
D.I. Mendeleyev University of Chemical Technology
Email: gordienko.m.g@muctr.ru
ORCID iD: 0000-0002-8485-9861
SPIN-code: 7148-5640
Dr.Sc. (Eng.), Associate Professor, Professor of the Department of Chemical and Pharmaceutical Engineering
Russian Federation, 9, building 1, Miusskaya Ploshchad, Moscow, 125047References
- Manabe T., Kambayashi D., Akatsu H. et al. Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis. BMC infectious diseases. 2021; 21(1): 489. doi: 10.1186/s12879-021-06164-x.
- Li H., Wang L., Xie G. et al. Cocrystals of favipiravir: improved physicochemical properties and solution stability study. Crystal Growth & Design. 2023; 23(12): 8656–8669. doi: 10.1021/acs.cgd.3c00805.
- Madden S., Carrazana E., Rabinowicz A.L. Optimizing absorption for intranasal delivery of drugs targeting the central nervous system using alkylsaccharide permeation enhancers. Pharmaceutics. 2023; 15(8): 2119. doi: 10.3390/pharmaceutics15082119.
- Wu H., Li C., Yuan H. et al. Brain Delivery Strategies for Biomacromolecular Drugs: Intranasal Administration. International Journal of Nanomedicine. 2025; 6463–6487. doi: 10.2147/IJN.S520768.
- Surya N., Bhattacharyya S. PLGA – the smart polymer for drug delivery. Pharmacy & Pharmacology. 2021; 9(5): 334-345. (In Russ.). doi: 10.19163/2307-9266-2021-9-5-334-345.
- Sapelnikov M.D., Nikolskaya E.D., Morozova N.B. et al. Development of the technology for obtaining PLGA and dipropoxybateriopurpurinimide-based nanoparticles. Evaluation of physicochemical and biological properties of the obtained delivery system. Biomedical Photonics. 2019; 8(1): 4–17. (In Russ.). doi: 10.24931/2413-9432-2019-8-1-4-17.
- Filatova E.V. Lekarstvenny`e sistemy` protivoopuxolevogo dejstviya na osnove mikrosfer iz poli-3-oksibutirata: Dis. … kand. biol. nauk. Moskva. 2019. (In Russ.).
- Bochkov P.O., Shevchenko R.V., Litvin A.A. et al. Factors, effecting on drug bioavailability. Pharmacokinetics and Pharmacodynamics. 2016; (1): 12–20. (In Russ.).
- Balabanyan V.Y., Gelperina S.E. Osnovnye mekhanizmy dostavki lekarstvennykh veshchestv v mozg s pomoshch'yu polimernykh nanochastic. Farmakokinetika i Farmakodinamika. 2012; 2: 3–9. (In Russ.).
- Karve S., Werner M.E., Cummings N.D. et al. Formulation of diblock polymeric nanoparticles through nanoprecipitation technique. Journal of visualized experiments: JoVE. 2011; 55: 3398. doi: 10.3791/3398.
- Gandhi S., Shastri D.H., Shah J. et al. Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport. Pharmaceutics. 2024; 16(4): 481. doi: 10.3390/pharmaceutics16040481.
- Bakhrushina E.O., Mikhel I.B., Kondratieva V.M. et al. In situ gels as a modern method of intranasal vaccine delivery. Problems of Virology. 2022; 67(5): 395–402. (In Russ.). doi: 10.36233/0507-4088-139.
- Gattani V., Dawre S. Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route. Journal of drug delivery science and technology. 2023; 79: 104082. doi: 10.1016/j.jddst.2022.104082
- Riaz M., Zaman M., Hameed H. et al. Lamotrigine-Loaded Poloxamer-Based Thermo-Responsive Sol–Gel: Formulation, In Vitro Assessment, Ex Vivo Permeation, and Toxicology Study. Gels. 2023; 9(10): 817. doi: 10.3390/gels9100817.
- Hirun N., Kraisit P., Tantishaiyakul V. Thermosensitive Polymer Blend Composed of Poloxamer 407, Poloxamer 188 and Polycarbophil for the Use as Mucoadhesive In Situ Gel. Polymers. 2022; 14(9): 1836. doi: 10.3390/polym14091836.
- Bahryushina E.O., Pomyutkina M.V., Popova A.A., Khodenok A.I., Demina N.B. Study of poloxamer 188 and polyethylene glycols influence on in situ systems thermoreversible properties. Problems of biological, medical and pharmaceutical chemistry. 2022; 25(10): 20–25. (In Russ.). doi: 10.29296/25877313-2022-10-00.
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