Spironolactone hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism: in silico studies, statistical optimization, ex vivo, and in vivo studies

被引:20
作者
Albash, Rofida [1 ]
Fahmy, Abdurrahman M. [2 ]
Hamed, Mohammed I. A. [3 ]
Darwish, Khaled M. [4 ]
El-Dahmy, Rania Moataz [5 ]
机构
[1] Misr Univ Sci & Technol, Coll Pharmaceut Sci & Drug Mfg, Dept Pharmaceut, Giza, Egypt
[2] Cairo Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Kasr El Aini St, Cairo 11562, Egypt
[3] Fayoum Univ, Fac Pharm, Dept Organ & Med Chem, Al Fayyum, Egypt
[4] Suez Canal Univ, Dept Med Chem, Fac Pharm, Ismailia, Egypt
[5] October 6 Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Cairo, Egypt
关键词
In silico study; spironolactone; hirsutism; dermatokinetic; local accumulation efficiency index; RESPONSE-SURFACE METHODOLOGY; VITRO CHARACTERIZATION; TRANSDERMAL DELIVERY; GROWTH-CONDITIONS; MEDIUM COMPONENTS; FORMULATION; DESIGN; NANOPARTICLES; PERMEATION; CERAMIDE;
D O I
10.1080/10717544.2021.1989089
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Spironolactone (SP) is a potassium sparing diuretic with antiandrogenic properties. This study aimed at formulating SP into hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism. HAECs were prepared by ethanol injection method, according to D-optimal design, after a proper in silico study. HAECs were evaluated by measuring their entrapment efficiency (EE%), particle size (PS), and polydispersity index (PDI). Optimal hyaluronic acid enriched cerosomes (OHAECs) were subjected to further in vitro and ex-vivo and in-vivo studies. The in silico study concluded better interactions between SP and phosphatidyl choline in presence of hyaluronic acid (HA) and high stability of their binding in water. The prepared HAECs had acceptable EE%, PS, and PDI values. The statistical optimization process suggested OHAEC containing 10.5 mg ceramide III and 15 mg HA, utilizing Kolliphor(R) RH40. OHAEC had EE% and PS of 89.3 +/- 0.3% and 261.8 +/- 7.0 nm, respectively. OHAEC was stable for up to 3 months. It also showed a mixed tubular and vesicular appearance under transmission electron microscope. The ex vivo and in vivo studies concluded better skin deposition and accumulation of SP from OHAEC. The histopathological study demonstrated the safety of OHAEC for topical application. Therefore, OHAEC could be considered as effective system for topical application of SP to manage hirsutism, with prolonged action, coupled with minimized side effects.
引用
收藏
页码:2289 / 2300
页数:12
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