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New Era of Ocular Drug Delivery Systems Based on Contact Lenses

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New Era of Ocular Drug Delivery Systems Based on Contact Lenses FABAD J. Pharm. Sci., 45, 2, 161-174, 2020 REVIEW ARTICLES New Era of Ocular Drug Delivery Systems Based on Contact Lenses Panoraia I. SIAFAKA* , Ayşe Pınar YAĞCILAR** , Neslihan ÜSTÜNDAĞ OKUR***º New Era of Ocular Drug Delivery Systems Based on Contact Kontakt Lenslere Dayalı Oküler İlaç Taşıyıcı Sistemlerde Lenses Yeni Dönem SUMMARY ÖZ Ocular drug delivery belongs to the most useful topical adminis- Oküler ilaç taşınması en kullanışlı topikal ilaç uygulama yol- tration routes. Ocular drugs are applied on the eye mostly as ocular larındandır. Oküler ilaçlar, çoğunlukla göz damlaları olarak drops. However, eye drops present many limitations such as poor göze uygulanır. Ancak göz damlaları gözde kalış süresinin kı- eye retention time and rapid drug removal from tear drainage. salığı ve gözyaşı drenajı ile hızlıca ortamdan uzaklaştırılma Currently, contact lenses as ophthalmic drug carriers have become gibi çeşitli sınırlamalar gösterir. Son dönemde, kontakt lensler very popular since they can extent the drug release time and ther- ilaç salım süresini ve terapötik etkinliğini arttırarak oftalmik apeutic efficacy. It seems that contact lenses which are applied to ilaç taşıyıcı sistemler olarak popüler olmaya başlamıştır. Gözün the anterior chamber present extremely increased bioavailability ön odacığına uygulanan ve düşük biyoyararlanıma sahip göz above 50% which compared to low bioavailability of eye drops is damlalarına kıyasla biyoyararlanımı %50’nin üzerinde artı- highly beneficial. Moreover, via the topical delivery of ocular drug ran kontakt lenslerin son derece faydalı olduğu görülmüştür. contact lenses side effects are diminished whereas patient compli- Ayrıca, oküler ilaç içeren kontakt lenslerin topikal uygulan- ance is improved. Despite their advantages, contact lenses as oph- masıyla yan etkiler azaltılırken hasta uyuncu da artırılmış- thalmic carriers have not been marketed yet. Nonetheless, the last tır. Avantajlarına rağmen oftalmik taşıyıcılar olarak kontakt decade, the research interest focused on developing novel contact lensler henüz piyasada satışa sunulmamıştır. Bununla birlikte, lenses which can deliver controllable the drugs to the eye. In this son on yılda yapılan araştırmalar kontrollü salım sağlayabilen review, we summarize the found on literature ocular drug deliv- yeni geliştirilen kontakt lenslere odaklanmıştır. Bu derlemede, ery systems based on contact lenses according to their compounds, literatürde bulunan bileşimlerine, tasarımlarına ve diğer ka- their designing methods as other characteristics. It can be said that rakteristiklerine göre kontakt lenslere dayalı oküler ilaç taşıyıcı in the foreseeable future more and more topical eye drug delivery sistemleri özetledik. Öngörülen gelecekte daha fazla topikal ilaç systems will be appeared and contact lenses seem to provide the taşıyıcı sistemlerinin ortaya çıkacağı ve kontakt lenslerin iste- most desirable characteristics. Thus, the drug loaded contact lenses nen özellikleri sağlayacağı söylenebilir. Bu yüzden ilaç yüklü will bring a new evolution on the current marketed ocular for- kontakt lensler güncel oküler formülasyonlara yeni gelişmeler mulations. To conclude, this review could be helpful for medical getirecektir. Sonuç olarak, bu derleme sağlık profesyonelleri, of- professionals, ophthalmologists and scientists of every subject who talmolojistler ve yeni oküler kontakt lens geliştirmek isteyen her want to develop novel ocular contact lenses. konudan araştırmacılar için yararlı olacaktır. Key Words: Ocular, Drug delivery, Contact lenses, Hydrogels, Anahtar kelimeler: Oküler, İlaç taşınması, Kontakt lens- Polymers, Drug design ler, Hidrojeller, Polimerler, İlaç tasarımı Received: 31.12.2019 Revised: 12.02.2020 Accepted: 12.02.2020 * ORCID: 0000-0001-7256-3230, Aristotle University of Thessaloniki, Faculty of Sciences, School of Chemistry, Thessaloniki, Greece ** ORCID: 0000-0001-5546-4601, University of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey *** ORCID: 0000-0002-3210-3747, University of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, Turkey º Corresponding Author: Neslihan ÜSTÜNDAĞ OKUR Phone: +90 216 418 96 16, E-mail: [email protected] 161 Siafaka, Yağcılar, Üstündağ Okur INTRODUCTION Üstündağ Okur et al., 2019) and ocular inserts such Ophthalmic diseases can be categorized as acute (R. as contact lenses (Alvarez-Lorenzo, Anguiano-Igea, Gupta, 2003) and chronic (N. Gupta & Kocur, 2014). Varela-García, Vivero-Lopez, & Concheiro, 2019) and In most cases, ocular diseases are not life-threatening, films (Kapoor & Chauhan, 2008; Üstündağ-Okur et however, if they left untreated can lead to blindness al., 2014; Üstündağ-Okur et al., 2015) are applied as or blurred vision. Eye is very complex organ and thus possible sustained release drug carriers. The contact ocular drug delivery belongs to the most challeng- lenses seem to provide various promising character- ing field of drug administration routes (Siafaka et al., istics and thus should be further evaluated in clinical 2015; Üstündağ-Okur et al., 2014; Üstündağ-Okur, trials and in vivo studying. Yoltas, & Yozgatli, 2016; Üstündağ-Okur et al., 2015). Currently, topical application of ocular drugs is pre- Contact lenses (CLs) are ocular prosthetics devic- ferred since the systemic administration cannot reach es placed on the eye surface. They are widely used for eye efficiently (Başaran & Yazan, 2012). As topical eye correcting vision, aesthetics and therapeutic appli- formulations and most marketed products are used cations (Farandos, Yetisen, Monteiro, Lowe, & Yun, the conventional eye drops or suspensions. Howev- 2015). The first corneal lenses were developed, in 1949 er, such formulations demonstrate very low ocular bioavailability and thus should be frequently dosing. whereas on 1960 the first corneal lenses based on poly Their low bioavailability resulted from various factors, (methyl methacrylate)-PMMA were used. In present, such as rapid removal of drug due to nasolacrimal CLs are manufactured by PMMA, poly (hydroxyleth- drainage, tearing and blinking as well as low permea- yl methacrylate)- PHEMA (Achilias & Siafaka, 2017; bility of the corneal membrane (Maulvi, Soni, & Shah, Achilias, Siafaka, & Nikolaidis, 2012) and other ma- 2016; Siafaka et al., 2015; Üstündağ Okur, Yozgat- terials such as silicone and poly (vinyl alcohol)-PVA, lı, Okur, Yoltaş, & Siafaka, 2019). Due to the above, (Musgrave & Fang, 2019) (Figure 1). PMMA was first novel formulations are designed aiming to overcome applied as CL compound however due to its limited such drawbacks. Colloidal suspensions (Siafaka et al., oxygen permeability, it was replaced by PHEMA. The 2015), matrix systems, liposomes (Taha, El-Anazi, El-Bagory, & Bayomi, 2014), microemulsions (Ke- manufacture of optimal CLs associated strictly with savan, Kant, Nath Singh, & Kumar Pandit, 2013), the macromolecule and its polymerization conditions dendrimers (Chaniotakis, Thermos, & Kalomira- such as temperature, initiator type, polymerization ki, 2016), in–situ gels (Üstündağ-Okur et al., 2016; mechanism (Musgrave & Fang, 2019) etc. Figure 1. The chemical structures of common polymers develop CLs 162 FABAD J. Pharm. Sci., 45, 2, 161-174, 2020 Contact lenses (CLs) as drug delivery systems 3 minutes of eye drops to more than 30 minutes. Thus, were first introduced in 1965 by Sedlacek (Kumar & the ocular bioavailability is also improved whereas Jha, 2011). It has been reported that as drug eluting dose frequency is eliminated and the drug is absorbed CLs, the silicone hydrogels and other hydrogels are of and reaches target ocular tissues. In addition, the drug the most optimal candidates (Jiawen Xu et al., 2018). systemic absorption is avoided and the related side ef- Mostly, CLs are used as therapeutic tools for ocular fects are also diminished (Kumar & Jha, 2011; Maulvi surface and anterior chamber disorders. Besides, CLs et al., 2016). have been reported to be applied as posterior segment The preparation methods for the development of diseases management (Guzman-Aranguez, Colligris, CLs loaded drugs (Figure 2) are: a) soaking meth- & Pintor, 2013). From pharmacological aspect, anti- od, b) molecular imprinting and c) encapsulation of microbials, corticoids, anti-inflammatory, immuno- colloidal nanoparticles into CLs. In case of soaking suppressants, lowering of ocular pressure agents are method, CLs are soaked in drug suspension, followed loaded in contact lenses so as to treat various diseases by drug uptake and release in pre- and post-lens tear (Holgado, Anguiano-Domínguez, & Martín-Ban- film. This method which is the easiest handled tech- deras, 2020). In further, CLs intended to be used as nique presents various disadvantages such as burst drug carriers should possess comfort, cytocompati- effect and rigorous release. On the other hand, the bility and prolonged release (Ciolino et al., 2009). In retention time compared to the conventional formu- fact, CLs present unique features such as increased lations is improved (Bengani, Hsu, Gause, & Chau- bioavailability, extended wear time and improved re- han, 2013; Hehl, Beck, Luthard, Guthoff, & Drewelow, tention time. Considering that the contact lenses are 1999; Peterson, Wolffsohn, Nick, Winterton, & Lally, solid formulation can extent retention time from 1 to 2006). Figure 2. A schematic illustration of preparation methods of drug loaded CLs The second technique molecular imprinting polymerized.
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