Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone
Abstract
:1. Introduction
2. Results and Discussion
2.1. Encapsulation Efficiency of Dexa (%) and Dexa Loading Efficiency (%)
2.2. Lmp and Lmp/Dexa Structure Characterization
2.2.1. Fourier-Transform Infrared Spectroscopy
2.2.2. X-ray Diffraction
2.2.3. Thermal Analysis
2.2.4. Optical Microscopy
2.2.5. SEM
2.3. Lmp/Dexa Charateristics
2.3.1. In Vitro Release Study
2.3.2. Cytotoxicity Assay of Lmp and Lmp/Dexa
Cell Viability Assays
Protective Effect of Dexamethasone and Dexamethasone-Loaded Lmp against Cisplatin
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Methods
4.2.1. Preparation of Lipid/Pectin/BSA Microparticles (Lmp)
4.2.2. Preparation of Dexa-Loaded Lipid/Pectin/BSA Microparticles (Lmp/Dexa)
4.2.3. Fluorescent Lmp and Lmp/Dexa Samples Preparation
4.2.4. Suspensions of Lmp and Lmp/Dexa in PBS and Physical Mixture of Pure Dexa with Lmp
4.2.5. Encapsulation Efficiency of Dexa and Dexa Loading Efficiency in Lmp/Dexa
4.2.6. Methods for Structural Characterization of Lmp and Lmp/Dexa
FTIR Spectroscopy
X-ray Diffraction
Thermal Analysis
Optical Microscopy
Scanning Electron Microscopy (SEM)
4.2.7. Methods for the Study of Lmp/Dexa Characteristics
In Vitro Release Study
Cytotoxicity Assay of Lmp and Lmp/Dexa
- Cell Lines, Cultures, and Treatments
- 2.
- In Vitro Release Study
4.2.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- World Health Organization. World Report on Hearing. 2021. Available online: https://www.who.int/publications/i/item/world-report-on-hearing (accessed on 25 July 2022).
- Wilson, W.R.; Byl, F.M.; Laird, N. The Efficacy of Steroids in the Treatment of Idiopathic Sudden Hearing Loss: A Double-blind Clinical Study. Arch. Otolaryngol. 1980, 106, 772–776. [Google Scholar] [CrossRef] [PubMed]
- Kuhn, M.; Heman-Ackah, S.E.; Shaikh, J.A.; Roehm, P.C. Sudden Sensorineural Hearing Loss: A Review of Diagnosis, Treatment, and Prognosis. Trends. Amplif. 2011, 15, 91–105. [Google Scholar] [CrossRef]
- Shemirani, N.L.; Schmidt, M.; Friedland, D.R. Sudden sensorineural hearing loss: An evaluation of treatment and management approaches by referring physicians. Otolaryngol. Neck. Surg. 2009, 140, 86–91. [Google Scholar] [CrossRef]
- Waissbluth, S.; Peleva, E.; Daniel, S.J. Platinum-induced ototoxicity: A review of prevailing ototoxicity criteria. Eur. Arch. Oto-Rhino-Laryngol. 2017, 274, 1187–1196. [Google Scholar] [CrossRef]
- Breglio, A.M.; Rusheen, A.E.; Shide, E.D.; Fernandez, K.A.; Spielbauer, K.K.; McLachlin, K.M.; Hall, M.D.; Amable, L.; Cunningham, L.L. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat. Commun. 2017, 8, 1654. [Google Scholar] [CrossRef] [Green Version]
- Yu, D.; Gu, J.; Chen, Y.; Kang, W.; Wang, X.; Wu, H. Current Strategies to Combat Cisplatin-Induced Ototoxicity. Front. Pharmacol. 2020, 11, 999. [Google Scholar] [CrossRef] [PubMed]
- Hill, G.W.; Morest, D.K.; Parham, K. Cisplatin-Induced Ototoxicity: Effect of intratympanic dexamethoasone injections. Otol. Neurotol. 2008, 29, 1005–1011. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schreiber, B.E.; Agrup, C.; Haskard, D.O.; Luxon, L.M. Sudden sensorineural hearing loss. Lancet 2010, 375, 1203–1211. [Google Scholar] [CrossRef]
- Nyberg, S.; Abbott, N.J.; Shi, X.; Steyger, P.S.; Dabdoub, A. Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier. Sci. Transl. Med. 2019, 11, 1–12. [Google Scholar] [CrossRef]
- Williams, D.M. Clinical pharmacology of corticosteroids. Respir. Care 2018, 63, 655–670. [Google Scholar] [CrossRef] [Green Version]
- Dindelegan, M.G.; Blebea, C.; Perde-Schrepler, M.; Buzoianu, A.D.; Maniu, A.A. Recent Advances and Future Research Directions for Hearing Loss Treatment Based on Nanoparticles. J. Nanomater. 2022, 2022, 1–15. [Google Scholar] [CrossRef]
- Salt, A.N.; Plontke, S.K. Local inner-ear drug delivery and pharmacokinetics. Drug Discov. Today 2005, 10, 1299–1306. [Google Scholar] [CrossRef] [Green Version]
- Dormer, N.H.; Nelson-Brantley, J.; Staecker, H.; Berkland, C.J. Evaluation of a transtympanic delivery system in Mus musculus for extended release steroids. Eur. J. Pharm. Sci. 2019, 126, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Yang, K.-J.; Son, J.; Jung, S.Y.; Yi, G.; Yoo, J.; Kim, D.-K.; Koo, H. Optimized phospholipid-based nanoparticles for inner ear drug delivery and therapy. Biomaterials 2018, 171, 133–143. [Google Scholar] [CrossRef] [PubMed]
- Egli Gallo, D.; Khojasteh, E.; Gloor, M.; Hegemann, S.C. Effectiveness of systemic high-dose dexamethasone therapy for idiopathic sudden sensorineural hearing loss. Audiol. Neurotol. 2013, 18, 161–170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, X.; Chen, W.-J.; Xu, J.; Yi, H.-J.; Ye, J.-Y. Clinical Analysis of Intratympanic Injection of Dexamethasone for Treating Sudden Deafness. Int. J. Gen. Med. 2021, 14, 2575–2579. [Google Scholar] [CrossRef]
- Czock, D.; Keller, F.; Rasche, F.M.; Häussler, U. Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids. Clin. Pharmacokinet. 2005, 44, 61–98. [Google Scholar] [CrossRef]
- Liu, D.; Ahmet, A.; Ward, L.; Krishnamoorthy, P.; Mandelcorn, E.D.; Leigh, R.; Brown, J.P.; Cohen, A.; Kim, H. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin. Immunol. 2013, 9, 30. [Google Scholar] [CrossRef] [Green Version]
- Toniazzo, T.; Berbel, I.F.; Cho, S.; Fávaro-Trindade, C.S.; Moraes, I.C.; Pinho, S.C. β-carotene-loaded liposome dispersions stabilized with xanthan and guar gums: Physico-chemical stability and feasibility of application in yogurt. LWT 2014, 59, 1265–1273. [Google Scholar] [CrossRef]
- Guldiken, B.; Gibis, M.; Boyacioglu, D.; Capanoglu, E.; Weiss, J. Physical and chemical stability of anthocyanin-rich black carrot extract-loaded liposomes during storage. Food Res. Int. 2018, 108, 491–497. [Google Scholar] [CrossRef]
- Lin, W.; Goldberg, R.; Klein, J. Poly-phosphocholination of liposomes leads to highly-extended retention time in mice joints. J. Mater. Chem. B 2022, 10, 2820–2827. [Google Scholar] [CrossRef] [PubMed]
- Tan, C.; Wang, J.; Sun, B. Biopolymer-liposome hybrid systems for controlled delivery of bioactive compounds: Recent advances. Biotechnol. Adv. 2021, 48, 107727. [Google Scholar] [CrossRef] [PubMed]
- Shah, S.; Famta, P.; Raghuvanshi, R.S.; Singh, S.B.; Srivastava, S. Lipid polymer hybrid nanocarriers: Insights into synthesis aspects, characterization, release mechanisms, surface functionalization and potential implications. Colloids Interface Sci. Commun. 2021, 46, 100570. [Google Scholar] [CrossRef]
- Bhargavi, N.; Dhathathreyan, A.; Sreeram, K. Regulating structural and mechanical properties of pectin reinforced liposomes at fluid/solid interface. Food Hydrocoll. 2020, 111, 106225. [Google Scholar] [CrossRef]
- Zhou, W.; Liu, W.; Zou, L.; Liu, W.; Liu, C.; Liang, R.; Chen, J. Storage stability and skin permeation of vitamin C liposomes improved by pectin coating. Colloids Surfaces B Biointerfaces 2014, 117, 330–337. [Google Scholar] [CrossRef]
- Shao, P.; Wang, P.; Niu, B.; Kang, J. Environmental stress stability of pectin-stabilized resveratrol liposomes with different degree of esterification. Int. J. Biol. Macromol. 2018, 119, 53–59. [Google Scholar] [CrossRef] [PubMed]
- Prajapati, V.D.; Jani, G.K.; Moradiya, N.G.; Randeria, N.P. Pharmaceutical applications of various natural gums, mucilages and their modified forms. Carbohydr. Polym. 2013, 92, 1685–1699. [Google Scholar] [CrossRef] [PubMed]
- Rana, V.; Rai, P.; Tiwary, A.K.; Singh, R.S.; Kennedy, J.F.; Knill, C.J. Modified gums: Approaches and applications in drug delivery. Carbohydr. Polym. 2011, 83, 1031–1047. [Google Scholar] [CrossRef]
- Van Bracht, E.; Raavé, R.; Verdurmen, W.P.R.; Wismans, R.G.; Geutjes, P.J.; Brock, R.E.; Oosterwijk, E.; van Kuppevelt, T.H.; Daamen, W.F. Lyophilisomes as a new generation of drug delivery capsules. Int. J. Pharm. 2012, 439, 127–135. [Google Scholar] [CrossRef]
- Kratz, F. Albumin as a drug carrier: Design of prodrugs, drug conjugates and nanoparticles. J. Control. Release 2008, 132, 171–183. [Google Scholar] [CrossRef]
- Grinberg, O.; Hayun, M.; Sredni, B.; Gedanken, A. Characterization and activity of sonochemically-prepared BSA microspheres containing Taxol—An anticancer drug. Ultrason. Sonochemistry 2007, 14, 661–666. [Google Scholar] [CrossRef]
- Shen, H.J.; Shi, H.; Ma, K.; Xie, M.; Tang, L.L.; Shen, S.; Li, B.; Wang, X.-S.; Jin, Y. Polyelectrolyte capsules packaging BSA gels for pH-controlled drug loading and release and their antitumor activity. Acta Biomater. 2013, 9, 6123–6133. [Google Scholar] [CrossRef] [PubMed]
- Yu, S.; Hu, J.; Pan, X.; Yao, P.; Jiang, M. Stable and pH-sensitive nanogels prepared by self-assembly of chitosan and ovalbumin. Langmuir 2006, 22, 2754–2759. [Google Scholar] [CrossRef] [PubMed]
- Lu, B.; Xiong, S.-B.; Yang, H.; Yin, X.-D.; Zhao, R.-B. Mitoxantrone-loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases: I: Formulation and in vitro characterization. Int. J. Pharm. 2006, 307, 168–174. [Google Scholar] [CrossRef] [PubMed]
- Shah, S.; Dhawan, V.; Holm, R.; Nagarsenker, M.S.; Perrie, Y. Liposomes: Advancements and innovation in the manufacturing process. Adv. Drug Deliv. Rev. 2020, 154–155, 102–122. [Google Scholar] [CrossRef]
- Jaafar-Maalej, C.; Diab, R.; Andrieu, V.; Elaissari, A.; Fessi, H. Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation. J. Liposome Res. 2009, 20, 228–243. [Google Scholar] [CrossRef]
- Butler, M.F.; Glaser, N.; Weaver, A.C.; Kirkland, A.M.; Heppenstall-Butler, M. Calcium Carbonate Crystallization in the Presence of Biopolymers. Cryst. Growth Des. 2006, 6, 781–794. [Google Scholar] [CrossRef]
- Cipolla, D.; Wu, H.; Salentinig, S.; Boyd, B.; Rades, T.; Vanhecke, D.; Petri-Fink, A.; Rothin-Rutishauser, B.; Eastman, S.; Redelmeier, T.; et al. Formation of drug nanocrystals under nanoconfinement afforded by liposomes. RSC Adv. 2016, 6, 6223–6233. [Google Scholar] [CrossRef] [Green Version]
- Beck, R.; Pohlmann, A.; Hoffmeister, C.; Gallas, M.; Collnot, E.; Schaefer, U.; Guterres, S.; Lehr, C.-M. Dexamethasone-loaded nanoparticle-coated microparticles: Correlation between in vitro drug release and drug transport across Caco-2 cell monolayers. Eur. J. Pharm. Biopharm. 2007, 67, 18–30. [Google Scholar] [CrossRef] [PubMed]
- Gómez-Gaete, C.; Fattal, E.; Silva, L.; Besnard, M.; Tsapis, N. Dexamethasone acetate encapsulation into Trojan particles. J. Control. Release 2008, 128, 41–49. [Google Scholar] [CrossRef]
- Dukovski, B.J.; Plantić, I.; Čunčić, I.; Krtalić, I.; Juretić, M.; Pepić, I.; Lovrić, J.; Hafner, A. Lipid/alginate nanoparticle-loaded in situ gelling system tailored for dexamethasone nasal delivery. Int. J. Pharm. 2017, 533, 480–487. [Google Scholar] [CrossRef] [PubMed]
- Bucatariu, S.; Constantin, M.; Ascenzi, P.; Fundueanu, G. Poly(lactide-co-glycolide)/cyclodextrin (polyethyleneimine) microspheres for controlled delivery of dexamethasone. React. Funct. Polym. 2016, 107, 46–53. [Google Scholar] [CrossRef]
- Hsiao, I.L.; Gramatke, A.M.; Joksimovic, R.; Sokołowski, M.; Gradzielski, M.; Haase, A. Size and Cell Type Dependent Uptake of Silica Nanoparticles. J. Nanomed. Nanotechnol. 2014, 5, 248–258. [Google Scholar] [CrossRef]
- Kroll, A.; Dierker, C.; Rommel, C.; Hahn, D.; Wohlleben, W.; Schulze-Isfort, C.; Göbbert, C.; Voetz, M.; Hardinghaus, F.; Schnekenburger, J. Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays. Part. Fibre Toxicol. 2011, 8, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rees, K.R. Cells in Culture in Toxicity Testing: A Review. J. R. Soc. Med. 1980, 73, 261–264. [Google Scholar] [CrossRef] [Green Version]
- Perde-Schrepler, M.; Fischer-Fodor, E.; Virag, P.; Brie, I.; Cenariu, M.; Pop, C.; Valcan, A.; Gurzau, E.; Maniu, A. The expression of copper transporters associated with the ototoxicity induced by platinum-based chemotherapeutic agents. Hear. Res. 2020, 388, 107893. [Google Scholar] [CrossRef]
- Kalinec, G.; Thein, P.; Park, C.; Kalinec, F. HEI-OC1 cells as a model for investigating drug cytotoxicity. Hear. Res. 2016, 335, 105–117. [Google Scholar] [CrossRef]
- Pons, M.; Foradada, M.; Estelrich, J. Liposomes obtained by the ethanol injection method. Int. J. Pharm. 1993, 95, 51–56. [Google Scholar] [CrossRef]
- Charcosset, C.; Juban, A.; Valour, J.-P.; Urbaniak, S.; Fessi, H. Preparation of liposomes at large scale using the ethanol injection method: Effect of scale-up and injection devices. Chem. Eng. Res. Des. 2015, 94, 508–515. [Google Scholar] [CrossRef]
- Anitha, A.; Maya, S.; Deepa, N.; Chennazhi, K.; Nair, S.; Tamura, H.; Jayakumar, R. Efficient water soluble O-carboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells. Carbohydr. Polym. 2011, 83, 452–461. [Google Scholar] [CrossRef]
- Paşcalău, V.; Tertis, M.; Pall, E.; Suciu, M.; Marinca, T.; Pustan, M.; Merie, V.; Rus, I.A.; Moldovan, C.; Topala, T.; et al. Bovine serum albumin gel/polyelectrolyte complex of hyaluronic acid and chitosan based microcarriers for Sorafenib targeted delivery. J. Appl. Polym. Sci. 2020, 137, 1–16. [Google Scholar] [CrossRef]
- Kalinec, G.M.; Webster, P.; Lim, D.J.; Kalinec, F. A Cochlear Cell Line as an in vitro System for Drug Ototoxicity Screening. Audiol. Neurotol. 2003, 8, 177–189. [Google Scholar] [CrossRef]
- Devarajan, P.; Savoca, M.; Castaneda, M.; Park, M.S.; Esteban-Cruciani, N.; Kalinec, G.; Kalinec, F. Cisplatin-induced apoptosis in auditory cells: Role of death receptor and mitochondrial pathways. Hear. Res. 2002, 174, 45–54. [Google Scholar] [CrossRef]
- Kalinec, G.M.; Park, C.; Thein, P.; Kalinec, F. Working with Auditory HEI-OC1 Cells. J. Vis. Exp. 2016, 2016, e54425. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Dexa:Lipoid S100:DDAB Ratio | Dexa Encapsulation Efficiency (%) ± SD | Dexa Loading Efficiency (%) ± SD |
---|---|---|
2:10:1 | 83.07 ± 1.35 | 0.22 ± 0.007 |
3:10:1 | 89.86 ± 0.42 | 0.36 ± 0.009 |
4:10:1 | 92.5 ± 0.61 | 0.50 ± 0.01 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Dindelegan, M.G.; Pașcalău, V.; Suciu, M.; Neamțu, B.; Perde-Schrepler, M.; Blebea, C.M.; Maniu, A.A.; Necula, V.; Buzoianu, A.D.; Filip, M.; et al. Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone. Gels 2022, 8, 483. https://doi.org/10.3390/gels8080483
Dindelegan MG, Pașcalău V, Suciu M, Neamțu B, Perde-Schrepler M, Blebea CM, Maniu AA, Necula V, Buzoianu AD, Filip M, et al. Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone. Gels. 2022; 8(8):483. https://doi.org/10.3390/gels8080483
Chicago/Turabian StyleDindelegan, Maximilian George, Violeta Pașcalău, Maria Suciu, Bogdan Neamțu, Maria Perde-Schrepler, Cristina Maria Blebea, Alma Aurelia Maniu, Violeta Necula, Anca Dana Buzoianu, Miuța Filip, and et al. 2022. "Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone" Gels 8, no. 8: 483. https://doi.org/10.3390/gels8080483