The traditional ophthalmological dosage forms have a low bioavailability, 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 form

Baskakova, A. V.

DSpace at Belgorod State University

Мини-обзор Mini-review Научные результаты биомедицинских исследований. 2018. Т.4, №4. С. 31-34 Research Results in Biomedicine. 2018. Vol.4, №4. Р. 31-34 31 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 (aleksbaskakova@yandex.ru) 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 Bi-omedicine. 2018;4(4):31-34]. DOI: 10.18413/2313-8955-2018-4-4-0-4 Abstract Background: The traditional ophthalmological dosage forms have a low bioavaila-bility, a rapid precorneal clearance and a low corneal permeability. The gelling sys-tem or system with a prolonged action (prolonged eye-drops) may be overcome by the application of fibers. An innovative dosage form was described for ophthalmolo-gy 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 dif-ferent properties of pharmaceutical formulations appears to offer a synergy in bioa-vailability and sustained release with very comfortable conditions of use and pro-longed 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 meas-uring the citation impact of sources. Tasks: to describe suitable polymers for devel-opment 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 pa-thologies. The development of an ophthalmic insert with the possible introduction of several medicinal substances depending on the condition of each patient is promising. Мини-обзор Mini-review Научные результаты биомедицинских исследований. 2018. Т.4, №4. С. 31-34 Research Results in Biomedicine. 2018. Vol.4, №4. Р. 31-34 32 Keywords: nanofibers; electrospinning; ophthalmology; polymers; electrospun for-mulations; 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 rap-idly 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 sub-stances 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 pre-pared 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 ap-pears to offer a synergy in bioavailability and sustained release with very comfortable condi-tions of use and prolonged action. Novel for-mulations, such as prolonged eye-drops and gels or thinnest films for the eye, will be devel-oped 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(ɛ-caprolactone PCL Biodegradable thermoplastic polymer  Films, polymer for en-hancing of the the mechan-ical properties for engi-neered nanotopology of structures [3] poly(ethylene oxide) PEO Relatively high molecular weight, biocompatible mate-rial that effectively improves the mechanical and biological properties of composite hy-drogels In combination with chi-tosan is used for high an-timicrobial effect [4] polyvinyl alcohol PVA Presents biocompatibility, being prepared easily and having non-toxic solvent; wa-ter-soluble synthetic polymer; biodegradable Used for incorporate mol-ecules of biological origin, such as collagens, hyalu-ron and deoxyribonucleic acid[5] Мини-обзор Mini-review Научные результаты биомедицинских исследований. 2018. Т.4, №4. С. 31-34 Research Results in Biomedicine. 2018. Vol.4, №4. Р. 31-34 33 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, an-timicrobial, 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 poly-saccharide in nature;  Using for medical applica-tions[8] PCL is one of the most useful polymers in the medicine, but in ophthalmology, fibers were described in papers [1] and [9]. Both stud-ies report on fibers with antimicrobial agents. Karataş A. et all develop ofloxacin loaded elec-trospun fibers for ocular drug delivery. The mi-crobiological 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 incorpo-rated drug in fibers. That data is interesting for future development of dosage forms with anti-microbial agents for ophthalmology.  Simões S.M. [10] describes syringeable self-assembled cyclodextrin gels for drug de-livery: CDs were obtained in two systems to form inclusion complexes. Both types of com-plexes 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 αCD and βCD between polymer and sub-stances. 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 respon-sive 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 pro-duced by Aydogdu A et all. A uniform struc-ture of these fibers was achieved by increasing a polymer concentration, and their structure was semicrystalline. For next studies and com-bining 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 con-cept 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 wa-ter-, thermal-, and near-infrared (NIR) light- properties. Of course, the concentration of pol-ymers should be changed for drug develop-ment.  Karczewski A. et al have developed an antimicrobial drug delivery system [16] with PDS fibers. Chitosan, as a more adequate stim-ulus to facilitate the cell, was used in these fi-bers. This fiber shows an antimicrobial activity against all bacteria and is cell-friendly. The ex-perience in the use of these fibers have a poten-tial for ophtalmology drug development.  Мини-обзор Mini-review Научные результаты биомедицинских исследований. 2018. Т.4, №4. С. 31-34 Research Results in Biomedicine. 2018. Vol.4, №4. Р. 31-34 34 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 de-velopment of an ophthalmic insert with the possible introduction of several medicinal sub-stances depending on the condition of each pa-tient is promising. No conflict of interest was recorded with respect to this article. References 1. Baskakova A, Awwad S, Jiménez JQ, etal. Electrospun formulations of acyclovir, ciprof-loxacin and cyanocobalamin for ocular drug deliv-ery. 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, Corrêa 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. Fabrica-tion and characterization of a glucose-sensitive an-tibacterial 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. Anovel three dimensional scaffold for regenerative endodontics: materials and biological characteriza-tions. 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. Fabricationand 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. Karataş A, Algan AH, Pekel-BayramgilN, et al. Ofloxacin Loaded Electrospun Fibers for Ocular Drug Delivery: Effect of Formulation Vari-ables on Fiber Morphology and Drug Release. J Curr Drug Deliv. 2016;13(3):433-43. 10. Simões SM, Veiga F, Torres-LabandeiraJJ, 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 novelelectrospun hydroxypropyl methylcellu-lose/polyethylene oxide blend nanofibers: Mor-phology 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. BiomaterSci. Biphasic drug release from electrospun poly-blend nanofibers for optimized local cancer treat-ment. 2018 Jan 30;6(2):324-331. DOI: 10.1039/C7BM01018D 15. Bai Y, Zhang J, Chen X. A Thermal-, Wa-ter-, 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, etal.   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/j.joen.2017.08.024 Information about the author Alexandra V. Baskakova, Candidate of Pharma-ceutical Sciences, coordinator of R&D projects, FBIS "Central Research Institute of Epidemiology" of the Federal Service on Customers' Rights Protec-tion and Human Well-being Surveillance. E-mail: aleksbaskakova@yandex.ru 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. 

Perspective materials for drug delivery in the ophthalmic dosage form: a short review of polymers for electrospinning

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Perspective materials for drug delivery in the ophthalmic dosage form: a short review of polymers for electrospinning

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