A vaginal drug delivery model

Abstract

Efficient drug delivery at vaginal cavity is often a challenge owing to its peculiar physiological variations including vast differences in pH. Keeping in view this attribute of the target site, the current work was aimed at developing formulation strategies which could overcome this and successfully deliver molecules like itraconazole through SLNs. Optimized SLNs with the given composition was selected for further development into mucoadhesive and thermosensitive gel. Stearic acid and Compritol 888 (1:1, w/w ratio) as lipid, a mixture of 3% Poloxomer 188 and 0.5% sodium taurocholate as surfactant and organic to aqueous ratio of 10:50 was taken. Carbopol 934 and Pluronic F 127 were taken for the development of gel. Optimized gel exhibited a desired gelling temperature (35 C); viscosity (0.920 PaS) and appreciable in vitro drug release (62.2% in 20 h). MTT assay did not show any cytotoxic effect of the gel. When evaluated in vivo, it did not exhibit any irritation potential despite appreciable bioadhesion. A remarkable decrease in CFUs was also observed in comparison with control and marketed formulation when evaluated in rat infection model. Thus, the proposed study defines the challenges for developing a suitable formulation system overcoming the delivery barriers of the vaginal site.

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

“…The three formulations showed a sustained release profile of the drug, but only the 20% version had an ideal gelling temperature (35 °C). The in vivo tests confirmed the bioadhesion of the gel, the absence of irritation, and an increase of its antimicrobial effect with respect to the marketed formulations of the drug [ 110 ]. Also in the field of the vaginal delivery of antifungals, Rençber et al designed a mucoadhesive system containing another antifungal agent, clotrimazole, for the treatment of vaginal infections [ 111 ].…”

“…However, vaginal drug delivery is often limited because of the protective mechanisms of the vagina, including a wide range of physiological characteristics including pH variation, microflora, and cervical mucus. Particularly in the case of semi-solid formulations, the rapid physiological clearance of a vaginally-administered medication means poor drug retention, leakage, and a reduced duration of the therapeutic effects, all of which make multiple administrations necessary [ 89 , 110 ]. The development of mucoadhesive pharmaceutical formulations that have the ability to efficiently interact with the mucosal tissue of the vagina offers the possibility of prolonging the therapeutic effects of a drug, improving patient compliance, and decreasing the number of administrations necessary [ 127 ].…”

“…Itraconazole is marketed in two oral formulations, capsules and an emulsion, which are characterized by a bioavailability of approximately 30% and 55%, respectively [ 132 ]. Mirza et al developed a formulation made up of the drug encapsulated within solid lipid nanoparticles (SLNs) dispersed in a poloxamer P407-based gel [ 110 ]. They tested three percentages of poloxamer 407 (15%, 18%, 20% w / v ) enriched with carbopol CP 934 for its bioadhesive properties [ 133 ].…”

An effective vaginal gel to deliver CRISPR/Cas9 system encapsulated in poly (β-amino ester) nanoparticles for vaginal gene therapy

“…In addition, it avoids the hepatic first-pass effects and gastrointestinal fluids encountered by oral administration [45] . Nevertheless, one major difficulty for developing vaginal gene therapy drugs is the low delivery efficiency of exogenous DNA when going through the vaginal mucus [46] . Accordingly, mucoadhesive and mucus-penetrating systems were developed and exhibit possibilities to realize enhanced vaginal treatment [46] .…”

“…Nevertheless, one major difficulty for developing vaginal gene therapy drugs is the low delivery efficiency of exogenous DNA when going through the vaginal mucus [46] . Accordingly, mucoadhesive and mucus-penetrating systems were developed and exhibit possibilities to realize enhanced vaginal treatment [46] . Still, further development of an optimal formulation for the vaginal gene therapy is in urgent need [47] .…”