Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

Abstract

Abstract. This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosanemulsified NP showed the highest cellular uptake efficiency over PVA-and pluronic-emulsified NP (59.09±6.21%, 55.74±6.26%, and 62.54±3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA-and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Nanoparticles for drug delivery to the anterior segment of the eye

“…Besides contact lenses, other composite systems including implants, fibers or in situ gels were also used to load nanoparticles [218, 223]. Drugs including lidocaine [210], ciprofloxacin [219], levofloxacin [220], CsA [221, 222], timolol [213, 217], silver [224], meloxicam [225], dexamethasone [226–228], loteprednol etabonate [214], hydrocortisone butyrate [223], and resina draconis [218] have been loaded into the nanoparticles to be delivered through the composite systems. Four different methods have been used to prepare nanoparticle-laden therapeutic contact lenses.…”

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“…The increase in T g was also observed in case of PLGA as the endotherm of its pure spectra was observed at 47.5°C whereas this was seen at 52.3°C in the spectra of ACNs with PLGA. [23] Entrapment efficiency…”

Application of New Drug Delivery Systems for the Treatment of Bacterial Keratitis

“…tarafından, bakteriyel keratit tedavisine yönelik olarak yapılan bir çalışmada, hidrokortizon butirat yüklü poli [laktik-ko-glikolik asit (PLGA)] nanopartikülleri sürfaktan olarak polivinil alkol, pluronik F108 veya kitosan kullanılarak hazırlanarak, PLGA-PEG-PLGA termosensitiv jel içinde disperse edilmiş ve in vitro karaterizasyon çalışmaları gerçekleştirilmiştir. 89 Çalışmada, nanopartiküllerin jel içinde disperse edilmesiyle in vitro ilaç salımında patlama etkisinin (burst effect) engellenerek ideal bir hidrokortizon butirat salım profilinin elde edildiği belirtilmiştir. Ayrıca, insan kornea epitel hücreleri ile nanopartiküllerin inkübasyonu sonucu gerçekleştirilen hücre kültürü çalışmalarında 4.saat sonunda kitosan kullanılarak hazırlanan formülasyonların diğer formülasyonlara göre daha çok hücre içine alındığı, ancak 24. saat sonunda daha yüksek toksisite gösterdiği bulunmuştur.…”