Preparation and Characterization of Nanoparticular Systems For Topical Treatment of Ocular Infections

Abstract

Çalışmada, PLGA nanopartiküllere besifloksasin etken maddesi yüklenmiş ve elde edilen yapının bakteriyel konjuktivit tedavisi için kontrollü ilaç salım sistemi olarak kullanılabilirliği araştırılmıştır. Besifloksasin, sistemik bir formülasyon içermediği ve hem gram-pozitif hem de gram-negative patojenlere karşı etkili olduğu için seçilmiştir. Besifoksasinin topikal uygulama sonrasında, uygulama bölgesindeki kalım süresini uzatmak amacıyla nanopartiküler formülasyonu hazırlanmış ve etkinliği test edilmiştir. Bunun için, bu çalışmada besifloksasin PLGA nanopartiküllere yüklenmiş, karakterize edilmiş ve in vitro salım çalışmaları yapılmıştır. Ayrıca besifloksasin yüklü PLGA nanopartiküllerin toksisitesi belirlenmiştir. Nanopartiküller, morfolojik yapısı taramalı elektron mikroskobu, boyut ve yük analizi Zeta Sizer, fizikokimyasal yapısı Fourier Dönüşümü Kızılötesi Spektrometresi (FTIR) ile karakterize edilmiştir. Zeta Sizer sonuçlarına göre nanopartiküllerin ortalama 200nm boyutuna sahip olduğu belirlenmiştir ve SEM görüntüleri de sonuçları destekler niteliktedir. Nanopartiküllerden besifloksasinin salım patterninin, burst effect şeklinde olmayıp daha yavaş ve kontrollü bir şekilde salındığı görülmüştür.

Keywords

• PLGA nanoparticles,besifloxacin,drug delivery systems,eye infection

References

1. 1- W. Zhang, M. R. Prausnitz, A. Edwards, Modal of transient drug diffusion across cornea. J Controlled Release, 99 (2004) 241-58.
2. 2- P. K. Indu, R. Smitha, Penetration enhancers and ocular bioadhesive: two new avenues for ophathalmic drug delivery, Drug Devel Ind Pharm, 28 (2002) 353-69.
3. 3- R. Gaudana, H. K. Ananthula, A. Parenky, A. K. Mitra, Ocular drug delivery. The AAPS journal. 12 (2010) 348–360. 4- D. R. Janagam, L. Wu, and T. L. Lowe, Nanoparticles for drug delivery to the anterior segment of the eye, Advanced Drug Delivery Reviews, 122 (2017) 31-64.
4. 5- R. Katara, S. Sachdeva, D. K. Majumdar, Enhancement of ocular efficacy of aceclofenac using biodegradable PLGA nanoparticles:formulation and characterization, Drug Delivery and Translational Research, 7 (2017) 632-641.
5. 6- H. A. Salama, M. Ghorab, A. A. Mahmoud, M. A. Hady, PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma, AAPS PharmSciTech, 18 (2017) 2517-2528.
6. 7- F. S. Mah, C. M. Sanfilippo, Besifloxacin:Efficacy and Safety in Treatment and Prevention of Ocular Bacterial Infections, Ophthalmol Ther., 5 (2016) 1-20.
7. 8- W. Haas , C. M. Pillar, G. E. Zurenko, J. C. Lee, L. S. Brunner, T. W. Morris, Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria, Antimicrobial Agents and Chemotherapy, 53 (2009) 3552-3560.
8. 9- J. Yoshida, A. Kim, K. A. Pratzer, W. J. Stark, Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besifloxacin 0.6% ophthalmic suspension in cataract surgery patients, Journal of Cataract and Refractive Surgery, 36 (2010) 1499-1502.

9. 10- V. Arulmozhi, K. Pandian, S. Mirunalini, Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB), Colloids and Surfaces B: Biointerfaces, 110 (2013) 313–320.
10. 11- H. S. Yoo, K. H. Lee, J. E. Oh, T. G. Park, In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin-PLGA conjugates, Journal of Controlled Release, 68 (2000) 419-431.
11. 12- C. Fonseca, S. Simoes, R. Gaspar, Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity, Journal of Controlled Release, 83 (2002) 273–286.
12. 13- N. Pirooznia, S. Hasannia, A. S. Lotfi, M. Ghanei, Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In vitro characterization as an effective aerosol formulation in pulmonary diseases, Journal of Nanobiotechnology, 10 (2012) 1-15.
13. 14- H. Gupta, M. Aqil, R.K. Khar, A. Ali, A. Bhatnagar, G. Mittal, Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomedicine: NBM, 6 (2010) 324-333.
14. 15- A. M. Badawy, A. M. Badawy, A. K. Attia, A. E. Abd-Elaleem, M. M. Abd-Elmoety, S. G. Abd-Elhamid, Spectrophotometric and Spectrodensitometric Determination of Sparfloxacin and Besifloxacin Hydrochlorides in Presence of Their Peroxide Degradation Products, International Journal of Pharmaceutical Analysis, 40 (2015) 1254-1268.
15. 16- S.M. Agnihotri, P.R. Vavia, Diclofenac-loaded biopolymeric nanosuspensions for ophthalmic application. Nanomedicine: NBM, 5 (2009) 90-95.
16. 17- W. Vishakha, S. Ravindranath, Formulation Development and Evaluation of pH Triggered in situ Ophthalmic Gel of Besifloxacin Hydrochloride, Journal of Drug Delivery & Therapeutics, 8 (2018) 313-321.
17. 18- B. Saha, R. P. Patel, Formulation and evaluation of niosomal in situ gel of Besifloxacin hydrochloride Ocular delivery system, University Journal of Research, 2 (2017) 82-95.
18. 19- P. Aksungur, M. Demirbilek, E. B. Denkbaş, N. Ünlü, Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations, Journal of Microencapsulation, 29 (2012) 605–613.
19. 20- C. Fonseca, S. Simoes, R. Gaspar, Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity, Journal of Controlled Release, 83 (2002) 273-286.
20. 21- M. E. Sanders, Q. C. Moore, E. W. Norcross, A. Shafiee, M. E. Marquart, Efficacy of besifloxacin in a rabbit model of methicilline-resistant Staphylococcus aureus keratitis, Cornea, 28 (2009) 1055-1060.