Development of amphotericin B nanosuspensions for fungal keratitis therapy: effect of self-assembled γ-cyclodextrin

Jansook Phatsawee; Maw Phyo Darli; Soe Hay Man Saung Hnin; Chuangchunsong Ravinsinee; Saiborisuth Kitisak; Payonitikarn Nawaporn; Autthateinchai Rinrapas; Pruksakorn Patamaporn

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자료유형: 학술저널

저자정보: Jansook Phatsawee (Chulalongkorn University Thailand) Maw Phyo Darli (Chulalongkorn University Thailand) Soe Hay Man Saung Hnin (Chulalongkorn University Thailand) Chuangchunsong Ravinsinee (Chulalongkorn University Thailand) Saiborisuth Kitisak (Chulalongkorn University Thailand) Payonitikarn Nawaporn (Chulalongkorn University Thailand) Autthateinchai Rinrapas (Ministry of Public HealthThailand) Pruksakorn Patamaporn (Ministry of Public HealthThailand)

저널정보: 한국약제학회 Journal of Pharmaceutical Investigation Journal of Pharmaceutical Investigation 제50권 제5호

발행연도: 2020.1

수록면: 513 - 525 (13page)

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Propose Fungal keratitis is one of the major causes in loss of vision and blindness. Amphotericin B (AmB) is the first-line treatment of keratitis caused by Candida spp. and related fungi. Due to its high molecular weight and low aqueous solubility, it hampers the ocular bioavailability. It is well-known that γ-cyclodextrin (γCD) can enhance AmB solubility. The aim of this study was to investigate the effect of the additives on γCD solubilization of AmB and develop AmB eye drop nanosuspensions. Methods 0.18% (w/v) AmB nanosuspensions containing either 0.25% (w/v) chitosan or 0.10% (w/v) phospholipids (PL) in aqueous γCD eye drop medium were prepared by using high pressure homogenization technique. Physicochemical properties, in vitro mucoadhesive, in vitro permeation, degree of AmB aggregation, hemolytic activity and in vitro antifungal test were determined. Results The physicochemical properties of the nanosuspensions containing AmB/γCD nanoaggregates were in the acceptable range. The particle size of all formulations was in nanometer range. The degree of aggregation was less than 2.0 that meant the drug was not in the aggregate form when solubilized in γCD. These formulations demonstrated relatively low hemolytic activity and effectively improved the antifungal activity. Conclusion AmB/γCD nanosuspension stabilized by 0.10% (w/v) PL is the promising formulation for further studies due to that it was excellent physical appearance, had mucoadhesive property, enhanced in vitro permeation, had low toxicity and improved the antifungal activity.

#Amphotericin B #Cyclodextrin #Nanosuspensions #Solubilizer #Aggregates

참고문헌 (47)

참고문헌 신청

Akshay K / 2014 / Development of albendazole nanosuspension by various techniques / Drug Deliv Lett 4(2):87~95

Ansari Z / 2013 / Current thoughts in fungal keratitis : diagnosis and treatment / Curr Fungal Infect Rep 7(3):209~218

Banker GS / 2002 / Modern pharmaceutics / Marcel Dekker

Barwicz J / 1992 / Effects of the aggregation state of amphotericin B on its toxicity to mice / Antimicrob Agents Chemother 36(10):2310~2315

Bin Choy Y / 2008 / Mucoadhesive microparticles engineered for ophthalmic drug delivery / J Phys Chem Solids 69(5-6):1533~1536

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