<i>In Situ</i> Hydrogel Formulation for Intra-Articular Application of Diclofenac Sodium-Loaded Polymeric Nanoparticles

Abstract

Objectives: The world's population is getting older and the number of people suffering from arthritis is a major problem according to World Health Organization's data. In this respect, the need for more efficient treatment for arthritis becomes an urgent issue. In this research, nanoparticle bearing in situ gelling hydrogel formulation was developed for prolonged local delivery of diclofenac sodium (DS). Materials and Methods: Emulsion-solvent evaporation technique was used for the preparation of nanoparticles. Particle size, encapsulation efficiency, morphology, and drug release profile of DS loaded biodegradable nanoparticles as well as gel viscosity and gelation time of in situ gelling hydrogel formulations were optimized to increase the time interval between each dose application for enhanced patience compliance. Results:The spherical nanoparticles with a mean particle diameter of 168 nm was obtained and confirmed by both transmission electron microscope and atomic force microscope. Different types of surfactants were tested in the first emulsification step of nanoparticle production process and Arlacel ® -C significantly increased the encapsulation efficiency to 89.7%. Thirty days prolonged in vitro release of DS was achieved by using the combined formulation of polymeric nanoparticles and in situ hydrogel prepared by using poloxomer 407 and chitosan. Conclusion: Local administration of DS with this novel delivery system could be considered of having potential to minimize side effects associated with decreased amount of drug in dosage form compared to conventional oral dose. Key words: Diclofenac sodium, drug delivery, PLGA, Poly(ε-caprolactone), thermosensitive hydrogel, poloxamers ABSTRACT ÖZ Amaç: Dünya Sağlık Örgütü'nün verilerine göre dünya çapında insanların yaş ortalaması ve bağlantılı olarak artrit hastalığından mağdur olan insan sayısı da artmaktadır. Bu açıdan bakıldığında, artrit tedavisi için daha etkili tedavilerin gerekliliği önemli hale gelmiştir. Bu araştırmada, diklofenak sodyumun (DS) uzatılmış lokal taşınımı için nanopartikül içeren in situ hidrojel formülasyonları geliştirilmiştir. Gereç ve Yöntemler: Nanopartiküllerin hazırlanmasında emülsiyon-çözücü buharlaştırma yöntemi kullanılmıştır. DS yüklü nanopartiküllerin partikül büyüklüğü, enkapsülasyon etkinliği, morfolojisi ve ilaç salım profilleri ile in situ hidrojelin jel viskozitesi ve jelleşme süresi, hasta uyuncunu artırmak için her bir dozun uygulanması arasındaki zamanı artırmak amacıyla optimize edilmiştir. Bulgular: Ortalama partikül büyüklüğü 168 nm olan küresel nanopartiküller elde edilmiş ve geçirimli elektron mikroskobu ve atomik kuvvet mikroskobu ile desteklenmiştir. Nanopartikül üretim sürecinin ilk emülsifikasyon adımında farklı sürfaktanlar denenmiş ve Arlacel ® -C diklofenak sodyumun enkapsülasyon etkinliğini %89.7'ye yükseltmiştir. DS'nin 30 güne uzatılmış in vitro salımı, nanopartiküllerin ve poloksamer 407/kitozan ile hazırlanmış in situ hidrojelin kombine kullanılmasıyla başarılmıştır. Sonuç: DS'nin bu yenilikçi taşıy...

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