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Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

ABSTRACT: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery system for vaginal administration of protein therapeutics.

SUBMITTER: Li C

PROVIDER: S-EPMC5108605 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

Li ChunYan C Huang ZhiGang Z Liu ZheShuo Z Ci LiQian L Liu ZhePeng Z Liu Yu Y Yan XueYing X Lu WeiYue W

International journal of nanomedicine 20161110

Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutic ...[more]

PMID: 27877038

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Project description:BackgroundIntravaginal practices are commonly used by women to manage their vaginal health and sexual life. These practices could, however, affect intravaginal mucosal integrity. The objectives of this study were to examine evidence for associations between: intravaginal practices and acquisition of HIV infection; intravaginal practices and vaginal infections; and vaginal infections and HIV acquisition.Methodology/principal findingsWe conducted a systematic review of prospective longitudinal studies, searching 15 electronic databases of journals and abstracts from two international conferences to 31(st) January 2008. Relevant articles were selected and data extracted in duplicate. Results were examined visually in forest plots and combined using random effects meta-analysis where appropriate. Of 2120 unique references we included 22 publications from 15 different studies in sub-Saharan Africa and the USA. Seven publications from five studies examined a range of intravaginal practices and HIV infection. No specific vaginal practices showed a protective effect against HIV or vaginal infections. Insertion of products for sex was associated with HIV in unadjusted analyses; only one study gave an adjusted estimate, which showed no association (hazard ratio 1.09, 95% confidence interval, CI 0.71, 1.67). HIV incidence was higher in women reporting intravaginal cleansing but confidence intervals were wide and heterogeneity high (adjusted hazard ratio 1.88, 95%CI 0.53, 6.69, I(2) 83.2%). HIV incidence was higher in women with bacterial vaginosis (adjusted effect 1.57, 95%CI 1.26, 1.94, I(2) 19.0%) and Trichomonas vaginalis (adjusted effect 1.64, 95%CI 1.28, 2.09, I(2) 0.0%).Conclusions/significanceA pathway linking intravaginal cleaning practices with vaginal infections that increase susceptibility to HIV infection is plausible but conclusive evidence is lacking. Intravaginal practices do not appear to protect women from vaginal infections or HIV and some might be harmful.

Project description:Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs' bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (??). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.

Project description:In this study, we fabricated and evaluated luliconazole-loaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box-Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78° for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

Dataset Information

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

Publications

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

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