PLGA NANOPARTICLES LOADED MUCOADHESIVE AND THERMOSENSITIVE HYDROGEL AS A POTENTIAL PLATFORM FOR THE TREATMENT OF ORAL MUCOSITIS

Authors

  • Gina S. El-feky Department of Pharmaceutical Technology, National Research Center,
  • Gamal M. Zayed Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University at Assiut, Egypt, Al-Azhar Centre of Nanosciences and Applications (ACNA), Assiut, Egypt

DOI:

https://doi.org/10.22159/ijap.2019v11i1.29466

Keywords:

Mucositis, PLGA nanoparticles, Thermosensitive hydrogel, Mucoadhesive hydrogel, In vivo

Abstract

Objective: The objective of this study was to design an effective topical treatment for oral mucositis.

Methods: Poly-(DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and Poloxamer407 (PLX)/Hydroxy propyl methyl cellulose (HPMC) hydrogel matrix (HG) were used as combined carriers for benzydamine HCL (BNZ). BNZ loaded PLGA nanoparticles were assessed for their particle size, PDI, zeta potential and entrapment efficiency. Scanning electron microscopy, thermosensitivity study, mucoadhesion study, in vitro release and in vivo investigation were used to characterize the combined BZN loaded PLGA NPs HG.

Results: Negatively charged NPs with an average diameter of 139±4.92 nm were incorporated into PLX/HPMC HG bases. The gelation temperature of BZN-PLGA-NPs-HGs ranged between 31°C and 36.5°C. When diluted with saliva simulated fluid, BZN-PLGA-NPs-HGs preserved their gelation properties. Mucoadhesion was found lower for formulations prepared with PLX without HPMC. An increase in the concentrations of PLX from 10 to 30% resulted in an increase in adhesion. Both PLGA-NPs and PLGA-NPs-HG provided a biphasic drug release profile while BZN-HG provided monophasic zero order release pattern. The in vivo study showed that animal groups treated with BZN-HG and BZN-PLGA-NPs-HG showed a significantly higher reduction percentage in ulcer surface area compared to those treated with BZN-PLGA-NPs. BZN-PLGA-NPs-HG group needed 10 d of treatment to complete healing versus 16 d, 14 d and 12 d for the complete healing of groups with no treatment, treated with BZN-PLGA-NPs and treated with BZN-HG, respectively.

Conclusion: BZN-PLGA-NPs-HG could represent a promising mean for the effective treatment of oral mucositis induced by cancer therapy.

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References

Harris DJ. Cancer treatment-induced mucositis pain: strategies for assessment and management. Ther Clin Risk Manag 2006;2:251-8.

Berger AM, Fall-Dickson JM. Oral complications. In: Principles and practice of oncology. 7th ed. DeVita VT. Lippincott Williams and Wilkins, Philadelphia, PA, USA; 2005. p. 2523–35.

Cinausero M, Aprile G, Ermacora P, Basile D, Vitale MG, Fanotto V, et al. New Frontiers in the pathobiology and treatment of cancer regimen-related mucosal injury. Front Pharmacol 2017;8:354.

Al-Ansari S, Zecha JAEM, Barasch A, de Lange J, Rozema FR, Raber Durlacher JE. Oral mucositis induced by conventional cytotoxic cancer therapies is a common and significant clinical problem in oncology. Curr Oral Health Rep 2015;2:202-11.

Panahi Y, Ala S, Saeedi M, Okhovatian A, Bazzaz N, Naghizadeh MM. Allopurinol mouth rinse for prophylaxis of fluorouracilâ€induced mucositis. Eur J Cancer Care 2010;19:308-12.

Epsteın JB, Sılverman S, Paggıarıno JR, Crockett DA, Schubert S, Senzer MM, et al. Benzy-damine HCl for prophylaxis of radiation induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer 2001;92:875-85.

De Laat EH, Scholte Op, Reimer WJ, Van Achterberg T. Pressure ulcers: diagnostics and interventions aimed at wound-related complaints: a review of the literature. J Clin Nurs 2005;14:464-72.

Danhier F, Ansorena E, Silva JM, Coco R, Breton A, Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Controlled Release 2012;161:505-22.

Abdel Mottaleb MM, Beduneau A, Pellequer Y, Lamprecht A. Stability of fluorescent labels in PLGA polymeric nanoparticles: quantum dots versus organic dyes. Int J Pharm 2015;494:471-8.

Zhu X, Zeng X, Zhang X, Cao W, Wang Y, Chen H, et al. The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo. Nanomed: Nanotechnol Biol Med 2016;12:623-32.

Zhou YY, Du YZ, Wang L, Zhou JP, Hu FQ. Preparation and pharmacodynamics of stearic acid and poly (lactic-co-glycolic acid) grafted chitosan oligosaccharide micelles for 10-hydroxycamptothecin. Int J Pharm 2010;393:143-51.

Rinaldi S, Fortunati E, Taddei M, Kenny JM, Armentano I, Latterini L. Integrated PLGA-agnanocomposite systems to control the degradation rate and antibacterial properties. J Appl Polym Sci 2013;130:1185-93.

Bhati R, Nagrajan RK. A detailed review on oral mucosal drug delivery system. Int J Pharm Sci Res 2012;3:659-81.

Sohi H, Ahuja A, Ahmad FJ, Khar RK. Critical evaluation of permeation enhancers for oral mucosal drug delivery. Drug Dev Ind Pharm 2010;36:254-82.

Hamidi M, Azadi A, Rafiei P. Hydrogel nanoparticles in drug delivery. Adv Drug Delivery Rev 2008;60:1638-49.

Shaikh R, Raj Singh TR, Garland MJ, Woolfson AD, Donnelly RF. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci 2011;3:89-100.

Priya JH, John R, Alex A, Anoop KR. Smart polymers for the controlled delivery of drugs–a concise overview. Acta Pharm Sin B 2014;4:120-7.

Al Khateb K, Ozhmukhametova EK, Mussin MN, Seilkhanov SK, Rakhypbekov TK, Lau WM, et al. In situ gelling systems based on pluronic F127/Pluronic F68 formulations for ocular drug delivery. Int J Pharm 2016;502:70-9.

Bujnakova Z, Dutkova E, Balaz M, Turianicova E, Balaz P. Stability studies of As4S4 nanosuspension prepared by wet milling in poloxamer 407. Int J Pharm 2015;478:187-92.

De Souza, Ferreir SB, Moco TD, Borghi-Pangoni FB, Junqueira MV, Bruschi ML. Rheological, mucoadhesive and textural properties of thermoresponsive polymer blends for biomedical applications. J Mech Behavior Biomed Mat 2015;55:164-78.

Dewan M, Bhowmick B, Sarkar G, Rana D, Bain MK, Bhowmik M, et al. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. Int J Bio Macromol 2015;72:706-10.

Loh XJ, Goh SH, Li J. New biodegradable thermo-gelling copolymers having very low gelation concentrations. Biomacromology 2007;8:585-93.

Koffi AA, Agnely F, Ponchelb G, Grossiordb JL. Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine. Eur J Pharm Sci 2006;27:328-35.

Anlar S, Capan Y, Guven O, Gogus A, Dalkara T, Hincal AA. Formulation and in vitro-in vivo evaluation of buccoadhesive morphine sulphate tablets. Pharm Res 1994;11:231-6.

Mashru RC, Sutariya VB, Sankalia MG, Parikh PP. Development and evaluation of fast-dissolving film of salbutamol sulphate. Drug Dev Ind Pharm 2005;31:25-34.

Gohel MC, Parikh RK, Aghara PY, Nagori SA, Delvadia RR, Dabhi M. Application of simplex lattice design and desirability function for the formulation development of mouth dissolving film of salbutamol sulphate. Curr Drug Delivery 2009;6:486-94.

de Sa FA, Taveira SF, Gelfuso GM, Lima EM, Gratieri T. Liposomal voriconazole (VOR) formulation for improved ocular delivery. Colloids Surf B 2015;133:331-8.

Shivakumar H, Yadav H. In vitro and in vivo evaluation of pH-sensitive hydrogels of carboxymethyl chitosan for intestinal delivery of theophylline. ISRN Pharm 2012;7:127-45.

Shimamura Y, Takeuchi I, Terada H, Makino K. A mouse model for oral mucositis induced by cancer chemotherapy. Anticancer Res 2018;38:307-12.

Choipang C, Chuysinuan P, Suwantong O, Ekabutr P, Supaphol P. Hydrogel wound dressings loaded with PLGA/ciprofloxacin hydrochloride nanoparticles for use on pressure ulcers. J Drug Delivery Sci Tech 2018;47:106-14.

Jeong YI, Na HS, Seo DH, Kim DG, Lee HC, Jang MK, et al. Ciprofloxacin-encapsulated poly (DL-lactide-co-glycolide) nanoparticles and its antibacterial activity. Int J Pharm 2008;352:31723.

Sun L, Liu Z, Wang L, Cun D, Tong HHY, Yan R, et al. Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. J Controlled Release 2017;254:45-54.

Abrego G, Alvarado HL, Egea MA, Gonzalez-Mira E, Calpena AC, Garcia ML. Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen. J Pharm Sci 2014b;103:3153-64.

Tugcu Demi̇roz F. Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. Marmara Pharm J 2017;21:762-70.

Joshi M, Bolmal U, Dandagi P. Formulation and evaluation of cefuroxime axetil sol gel for periodontits. Int J Pharm Pharm Sci 2014;6:498-503.

Liu T, Chu B. Formation of homogeneous gel-like phases by mixed triblock copolymer micelles in aqueous solution: FCC to BCC phase transition. J Appl Cryst 2000;33:727-30.

Cabana A, Ait-Kadi A, Juhasz J. Study of gelation process of polyethylene oxidea. J Colloid Interface Sci 1997;190:307-12.

Russo E, Selmin F, Baldassari S, Gennari CGM, Caviglioli G, Cilurzo F, et al. A focus on mucoadhesive polymers and their application in buccal dosage forms. J Drug Delivery Sci Technol 2016;32:113-25.

Smart JD, Kellaway IW, Worthington HE. An in vitro investigation of mucosa-adhesive materials for use in controlled drug delivery. J Pharm Pharmacol 1984;36:295-9.

Gu JM, Robinson JR, Leung SH. Binding of acrylic polymers to mucin/epithelial surfaces: Structure-property relationships. Crit Rev Ther Drug Carrier Syst 1988;5:21-67.

Ponchel G, Touchard F, Duchene D, Peppas NA. Bioadhesive analysis of controlled-release systems. I Fracture and interpenetration analysis in poly (acrylic acid)-containing systems. J Controlled Release 1987;5:129-41.

Parhi R. Development and optimization of pluronic® F127 and HPMC based thermosensitive gel for the skin delivery of metoprolol succinate. J Drug Delivery Sci Tech 2016;36:23-33.

Bader RA, Putnam DA. Engineering polymer systems for improved drug delivery. New Jersy, USA: Wiley; 2013.

Chatterjee B, Amalina N, Sengupta P, Mandal UK. Mucoadhesive polymers and their mode of action: a recent update. J Appl Pharm Sci 2017;7:195-203.

dos Santos TC, Rescignano N, Boff L, Reginatto FH, Simoes CMO, de Campos AM, et al. Manufacture and characterization of chitosan/PLGA nanoparticles nanocomposite buccal films. Carbohydrate Polymers 2017;173:638-44.

Dalpiaz A, Sacchetti F, Baldisserotto A, Pavan B, Maretti E, Iannuccelli V, et al. Application of the in-oil nanoprecipitation†method in the encapsulation of hydrophilic drugs in PLGA nanoparticles. J Drug Delivery Sci Tech 2016;32:283-90.

Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Delivery Rev 2010;62:83-99.

Kassab HJ, Thomas LM, Jabir SA. Development and physical characterization of a periodontal bioadhesive gel of gatifloxacin. Int J Appl Pharm 2017;9:31-6.

Mohawed OAM, Ashmoony MM, Gazayerly ON. Niosome-encapsulated clomipramine for transdermal controlled delivery. Int J Pharm Pharm Sci 2014;6:567-75.

Takeuchi I, Kamiki Y, Makino K. Therapeutic efficacy of rebamipide-loaded PLGA nanoparticles coated with chitosan in mouse model for oral mucositis induced by cancer chemotherapy. Colloids Surf B 2018;167:468-73.

Karavana (Hizarcioglu) SY, Sezer B, Guneri P, Veral A, Boyacioglu H, Ertan G, et al. Efficacy of topical benzydamine hydrochloride gel on oral mucosal ulcers: an in vivo animal study. Int J Oral Maxillofac Surg 2011;40:973-8.

Published

07-01-2019

How to Cite

El-feky, G. S., & Zayed, G. M. (2019). PLGA NANOPARTICLES LOADED MUCOADHESIVE AND THERMOSENSITIVE HYDROGEL AS A POTENTIAL PLATFORM FOR THE TREATMENT OF ORAL MUCOSITIS. International Journal of Applied Pharmaceutics, 11(1), 106–112. https://doi.org/10.22159/ijap.2019v11i1.29466

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