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ФАРМАКОЛОГИЯ, КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯ PHARMACOLOGY, CLINICAL PHARMACOLOGY
УДК 615.225:615.453.2
DOI: 10.18413/2313-8955-2018-4-4-0-4
Alexandra V. Baskakova
Perspective materials for drug delivery in the ophthalmic dosage form: a short review of polymers for electrospinning_
Federal Budget Institution of Science "Central Research Institute of Epidemiology" of the Federal Service on Customers' Rights Protection and Human Well-being Surveillance 3A Novogireevskaya St., Moscow, 111123, Russia Corresponding author: Alexandra V. Baskakova ([email protected])
Информация для цитирования: Baskakova A.V. Perspective materials for drug delivery in the ophthalmic dosage form: a short review of polymers for electrospin-ning // Научные результаты биомедицинских исследований. 2018. Т. 4, N 4. С. 31-34. [Baskakova AV. Perspective materials for drug delivery in the ophthalmic dosage form: a short review of polymers for electrospinning. Research Results in Biomedicine. 2018;4(4):31-34]. DOI: 10.18413/2313-8955-2018-4-4-0-4
Background: The traditional ophthalmological dosage forms have a low bioavaila-bility, a rapid precorneal clearance and a low corneal permeability. The gelling system or system with a prolonged action (prolonged eye-drops) may be overcome by the application of fibers. An innovative dosage form was described for ophthalmology and perspective drug development. The authors also conducted an overview of the polymers investigated in the production of films or tablets for oral dosage forms. The properties of fibers revealed fundamental differences from polymers. Combining different properties of pharmaceutical formulations appears to offer a synergy in bioavailability and sustained release with very comfortable conditions of use and prolonged action. Novel formulations, such as prolonged eye-drops and gels or thinnest films for the eye, will be developed and tested in vitro studies. This enhancement stipulates for perspective pharmaceutical development. The aim of the study: To describe the main types of fibers for the development of a potential ophthalmological dosage form. Materials and methods: The review of the articles with high CiteScore rating in Scopus and Web of Science. CiteScore is a simple way of measuring the citation impact of sources. Tasks: to describe suitable polymers for development of ocular dosage forms prepared by electrospinning. Results: The results of the review of the most useful polymers show that in most cases all polymers are used together. A huge number of ophthalmologic pathologies call for a correct approach to each nosology in each case. Conclusion: The electrospinning method will stipulate for the future development of customized tools for the treatment of ophthalmic pathologies. The development of an ophthalmic insert with the possible introduction of several medicinal substances depending on the condition of each patient is promising.
Abstract
Keywords: nanofibers; electrospinning; ophthalmology; polymers; electrospun formulations; ocular formulation; PVP; PEO; PVA; CDs; PDS; Chitosan; Cellulose
Introduction. Most ocular drugs when given by topical administration are rapidly cleared by the aqueous humor flowing into the anterior chamber and flushing the drug out via the trabecular meshwork, should they permeate the cornea. The drug will often therefore fail to reach reproducible therapeutic levels near the retina. Unfortunately, drugs in solution can rapidly clear within hours from the posterior cavity upon IVT injection. This reduces efficacy and frequent injections are required, which can lead to undesirable side effects and reduce patient compliance [1]. Electrospinning is one of the technics for production of different fibers for medical and pharmaceutical needs. This technic is being used to enhance the solubility substances in ophthalmology. We have conducted an overview of the polymers investigated in the production of films or tablets for oral dosage forms. Previous studies [1, 2] of electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery demonstrate that electrospun matrices, such as those prepared in this work, have potential for use as intravitreal implants and improve the solubility of such a water-insoluble substance like acyclovir.
The aim of this review is to describe the main types of fibers for the development of a potential ophthalmological dosage form.
Tasks: to describe suitable polymers for the development of ocular dosage forms prepared by electrospinning.
Results and discussion. The traditional ophthalmological dosage forms have a low bio-availability, a rapid precorneal clearance, and a low corneal permeability. The gelling system or system with a prolonged action (prolonged eye-drops) may be overcome by the application of fibers.
Anatomy of the eye is demonstrated in close connection with ophthalmic delivery and bioavailability of drugs. Combining different properties of pharmaceutical formulations appears to offer a synergy in bioavailability and sustained release with very comfortable conditions of use and prolonged action. Novel formulations, such as prolonged eye-drops and gels or thinnest films for the eye, will be developed and tested in vitro studies.
Table demonstrates the most useful types of polymers in ophthalmology.
Table
The most useful types of polymers in ophthalmology
Name of polymer Short name of polymer Properties Use
poly(e-caprolactone PCL Biodegradable thermoplastic polymer Films, polymer for enhancing of the the mechanical properties for engineered nanotopology of structures [3]
poly(ethylene oxide) PEO Relatively high molecular weight, biocompatible material that effectively improves the mechanical and biological properties of composite hydrogels In combination with chi-tosan is used for high antimicrobial effect [4]
polyvinyl alcohol PVA Presents biocompatibility, being prepared easily and having non-toxic solvent; water-soluble synthetic polymer; biodegradable Used for incorporate molecules of biological origin, such as collagens, hyalu-ron and deoxyribonucleic acid[5]
Cyclodextrins CDs Most versatile substances produced by nature Gels for drug delivery
Polydioxanone PDS Material for tissue regeneration [6] Biological matrix
Chitosan Chitosan Biodegradability, biocompat-ibility, it has fungicidal, antimicrobial, and antitumor activity and also has strong healing properties, as it offers an excellent environment for cell adhesion and prolifera-tion[7] Producing of membranes for regeneration
Cellulose Cellulose High molecular weight polysaccharide in nature; Using for medical applications^]
PCL is one of the most useful polymers in the medicine, but in ophthalmology, fibers were described in papers [1] and [9]. Both studies report on fibers with antimicrobial agents. Karata§ A. et all develop ofloxacin loaded elec-trospun fibers for ocular drug delivery. The microbiological study of properties of this fibers shows that freely released ofloxacin from fibers inhibited the growth of the tested bacteria. This study demonstrates that electrospinning had no adverse effects on the activity of the incorporated drug in fibers. That data is interesting for future development of dosage forms with antimicrobial agents for ophthalmology.
Simoes S.M. [10] describes syringeable self-assembled cyclodextrin gels for drug delivery: CDs were obtained in two systems to form inclusion complexes. Both types of complexes show stability with variety of drugs via interactions between substances and polymers. Functional groups of polymers are not involved in the other complexes. Other authors, Hu QD et all [11], describe the host-guest interactions of aCD and PCD between polymer and substances. They also report about modification of CDs with polymers due to the potential benefits rendered by cationic protection and improved capability. This modifications help to improve the controlled release by application of responsive structures.
Another benefit of using CDs for nano-medicine includes electrospun fibers of cy-clodextrins and poly(cyclodextrins) [12]. They include therapeutic agents. These complexes
demonstrate a slowl release that is the most suitable for a perspective ocular dosage form.
Cellulose fibers (HPMC in this studies) with polyethylene oxide PEO [13] were produced by Aydogdu A et all. A uniform structure of these fibers was achieved by increasing a polymer concentration, and their structure was semicrystalline. For next studies and combining PEO with HPMC the developments of uniform and stability fibers for ocular films may be interesting.
In the other studies of Kuang G et al, there were developed polyblend nanofibers for local cancer treatment [14]. PEO was included in the mixture of polymers as a hydrophilic polymer. This study will be used in a new concept of local chemotherapy.
Cellulose derivatives were prepared by incorporating polyaniline (PAn) fibers into pol-yvinyl alcohol (PVA) by Bai Y. [15]. These fibers are interesting for ophthalmological drug development because they show excellent water-, thermal-, and near-infrared (NIR) lightproperties. Of course, the concentration of polymers should be changed for drug development.
Karczewski A. et al have developed an antimicrobial drug delivery system [16] with PDS fibers. Chitosan, as a more adequate stimulus to facilitate the cell, was used in these fibers. This fiber shows an antimicrobial activity against all bacteria and is cell-friendly. The experience in the use of these fibers have a potential for ophtalmology drug development.
The results of the review of the most useful polymers show that in most cases all polymers are used together. A huge number of ophthalmologic pathologies call for a correct approach to each nosology in each case. The electrospinning method will stipulate for the future development of customized tools for the treatment of ophthalmic pathologies. The development of an ophthalmic insert with the possible introduction of several medicinal substances depending on the condition of each patient is promising.
No conflict of interest was recorded with respect to this article.
References
1. Baskakova A, Awwad S, Jiménez JQ, et al. Electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery. Int J Pharm. 2016 Apr 11;502(1-2):208-18. DOI: https://doi.org/10.1016/j.ijpharm.2016.02.015
2. Meireles AB, Correa DK, da Silveira JV, et al. Trends in polymeric electrospun fibers and their use as oral biomaterials. J Exp Biol Med (Maywood). 2018 May;243(8):665-676. DOI: https://doi.org/10.1177/1535370218770404
3. Battistella E, Varoni E, Cochis A, et al. Degradable polymers may improve dental practice. J Appl Biomater Biomech. 2011;9:223-31. DOI: https://doi.org/10.5301/JABB.2011.8867
4. Xiao Y, Gong T, Jiang Y, et al. Fabrication and characterization of a glucose-sensitive antibacterial chitosan-polyethylene oxide hydrogel. J Polymer. 2016;82:1-10. DOI: https: //doi .org/10.1016/j .polymer.2015.11.016
5. Kim GM, Asran AS, Michler GH, et al. Electrospun PVA/HAp nanocomposite nanofibers: biomimetics of mineralized hard tissues at a lower level of complexity. J Bioinspir Biomim. 2008;3:046003.
6. Bottino MC, Yassen GH, Platt JA, et al. A novel three dimensional scaffold for regenerative endodontics: materials and biological characterizations. J Tissue Eng Regen Med. 2015;9:116-23. DOI: https://doi.org/10.1002/term.1712
7. Furuya DC, Costa SA, Oliveira RC, et al. Fibers obtained from alginate, chitosan and hybrid used in the development of scaffolds. J Mat Res. 2017;20:377-86. DOI: http://dx.doi.org/10.1590/1980-5373-mr-2016-0509
8. Ao C, Niu Y, Zhang X, et al. Fabrication and characterization of electrospun cellulose/nano-hydroxyapatite nanofibers for bone tissue engineer-
ing. Int J Biol Macromol. 2017;97:568-73. DOI: https://doi.org/10.1016/j.ijbiomac.2016.12.091
9. Karata§ A, Algan AH, Pekel-Bayramgil N, et al. Ofloxacin Loaded Electrospun Fibers for Ocular Drug Delivery: Effect of Formulation Variables on Fiber Morphology and Drug Release. J Curr Drug Deliv. 2016;13(3):433-43.
10. Simöes SM, Veiga F, Torres-Labandeira JJ, et al. Syringeable self-assembled cyclodextrin gels for drug delivery. J Curr Top Med Chem. 2014;14(4):494-509.
11. Hu QD, Tang GP, Chu PK. Cyclodextrin-based host-guest supramolecular nanoparticles for delivery: from design to applications. Acc Chem Res. 2014 Jul 15;47(7):2017-25. DOI: 10.1021/ar500055s
12. Costoya A, Concheiro A, Alvarez-Lorenzo C. Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins). Molecules. 2017 Feb 3;22(2).
13. Aydogdu A, Sumnu G, Sahin S. A novel electrospun hydroxypropyl methylcellu-lose/polyethylene oxide blend nanofibers: Morphology and physicochemical properties. J Carbo-hydr Polym. 2018 Feb 1;181:234-246. DOI: https://doi.org/10.1016/j.carbpol.2017.10.071
14. Kuang G, Zhang Z, Liu S, et al. Biomater Sci. Biphasic drug release from electrospun poly-blend nanofibers for optimized local cancer treatment. 2018 Jan 30;6(2):324-331. DOI: 10.1039/C7BM01018D
15. Bai Y, Zhang J, Chen X. A Thermal-, Water-, and Near-Infrared Light-Induced Shape Memory Composite Based on Polyvinyl Alcohol and Polyaniline Fibers ACS Appl Mater Interfaces. 2018 Apr 25;10(16): 14017-14025. DOI: 10.1021/acsami.8b01425
16. Karczewski A, Feitosa SA, Hamer EI, et al. Clindamycin-modified Triple Antibiotic Nano-fibers: A Stain-free Antimicrobial Intracanal Drug Delivery System. J Endod. 2018 Jan;44(1):155-162. DOI: https://doi.org/10.1016/jjoen.2017.08.024
Information about the author Alexandra V. Baskakova, Candidate of Pharmaceutical Sciences, coordinator of R&D projects, FBIS "Central Research Institute of Epidemiology" of the Federal Service on Customers' Rights Protection and Human Well-being Surveillance. E-mail: [email protected]
Статья поступила в редакцию 30 мая 2018 г. Receipt date 2018 May 30.
Статья принята к публикации 2 сентября 2018 г. Accepted for publication 2018 September 2.
