Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is con...

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Bibliographic Details
Published in:Drug delivery 2018, Vol.25 (1), p.1328-1339
Main Authors: Aboud, Heba M., Hassan, Amira H., Ali, Adel A., Abdel-Razik, Abdel-Razik H.
Format: Article
Language:English
Subjects:
cubosomes
Drug delivery systems
Drug dosages
Glycerol
In vitro fertilization
in-situ gelling sponges
Infertility
Lipids
Particle size
Permeability
Pharmaceutical sciences
pharmacokinetic study
Pharmacy
Polyvinyl alcohol
Pregnancy
Sildenafil citrate
Studies
uterine targeting
Womens health
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Summary:Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is concerned with SIL uterine targeting following intravaginal administration via optimization of cubosomal in situ gelling sponges (CIS). An emulsification method was employed for preparation of cubosomal dispersions incorporating glyceryl monooleate as a lipid phase and poloxamer 407 as a surfactant with or without polyvinyl alcohol as a stabilizer. Cubosomes were estimated regarding entrapment efficiency (EE%), particle size, and in vitro drug release. Chitosan (2% w/w) was incorporated into the optimum formulation and then lyophilized into small sponges. For the CIS, in vivo histopathological and pharmacokinetic studies were conducted on female Wistar rats and compared with intravaginal free SIL sponges (FIS) and oral SIL solution. SIL-loaded cubosomes showed EE% ranging between 32.15 and 72.01%, particle size in the range of 150.81-446.02 nm and sustained drug release over 8 h. Histopathological study revealed a significant enlargement in endometrial thickness with congestion and dilatation of endometrial blood vessels in intravaginal CIS compared to intravaginal FIS and oral-treated groups. The pharmacokinetic study demonstrated higher AUC 0-∞ and C max with oral administration compared to intravaginal CIS or intravaginal FIS indicating potential involvement of first uterine pass effect after intravaginal administration. Finally, intravaginal CIS could be considered as a promising platform for SIL uterine targeting with minimized systemic exposure and side effects.
ISSN:1071-7544
1521-0464
DOI:10.1080/10717544.2018.1477858