Post-expansile hydrogel foam aerosol of PG-liposomes: A novel delivery system for vaginal drug delivery applications

摘要

The purpose of this work was to develop and characterize a novel delivery system of post-expansile hydrogel foam aerosol of propylene glycol-embodying liposomes (PG-liposomes) (PEHFL) for vaginal drug delivery applications. Matrine (MT) was used as a model drug to investigate the vaginal mucous membrane permeation behavior of MT from PEHFL versus PG-liposomes foam aerosol (PLFA), hydrogel foam aerosol (HFA) and hydrogel (HYG). The MT loaded PG-liposomes were characterized for shape, particle size, polydispersity, zeta potential and encapsulation efficiency; the foams of PEHFL were also characterized for swelling behavior, mucoadhesive force and duration. Results revealed that: (i) the MT loaded PG-liposomes had a mean size of 122 ± 16 nm, a good polydispersity index of 0.147 ± 0.023, and exhibited a negative charge of -47.5 ± 0.4 mV, the MT entrapment capacity in PG-liposomes (was calculated as percentages of total drug) was 80.8 ± 2.6%; (ii) the foams of PEHFL had a laggingly swelling process after spurted from a sealed container, and the higher the temperature of the surrounding environment, the greater the degree of swelling, this swelling state of foams would greatly enhance drug spread uniformly in vaginal canal and contact the vaginal walls tightly; (iii) the foams of PEHFL had a mucoadhesive force about 1460 ± 123 mN/cm 2, and could sustain 85 ± 11 min in vitro; (iv) the overall mean permeated MT through unit mass of porcine vaginal tissue from PEHFL was 2.64, 2.34 and 7.59 times higher than that from PLFA, HFA and HYG, respectively (t-test, P 0.05); and the quantity of MT remaining in the vaginal tissue at the end of the 12 h experiment was also significantly greater (t-test, P 0.05) from the PEHFL than from PLFA, HFA and HYG. All of these results indicate that the main advantages of PEHFL over conventional dosage forms are the ability to enhance the vaginal mucosa permeability of MT, spread uniformly in vaginal canal especially the highly folded epithelial surfaces, prolong the residence time at the site of administration and induce MT delayed release. In conclusion, the PEHFL may be a promising delivery system for vaginal delivery of medication.