Erratum: Author correction to 'Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system' [Acta Pharm Sin B 7 (2017) 593-602].

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].

Correction: Ci et al. Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer. Pharmaceutics 2019, 11, 15.

In the original publication [...].

Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer.

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.

Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system.

Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

Co-administration of tLyp-1 with polymeric paclitaxel conjugates: Enhanced intratumoral accumulation and anti-tumor efficacy.

BACKGROUND: It has been previously demonstrated that conjugation of paclitaxel to a linear poly(l-γ-glutamylglutamine) backbone can enhance water solubility of paclitaxel. However, intratumoral penetration of the nanoscale poly(l-γ-glutamylglutamine)-paclitaxel conjugate (PGG-PTX) was still limited due to dysfunctional tumor blood vessels as well as high interstitial pressure in the tumor microenvironment. PURPOSE: The objective of the present research was to investigate the feasibility of co-administration of a tumor penetration enhancing peptide tLyp-1 for improving intratumoral accumulation and consequent anti-tumor efficacy of PGG-PTX. METHODS: The influence of co-administration of tLyP-1 with PGG-PTX on intratumoral accumulation (via HPLC-MS/MS) and anti-tumor efficacy (by monitoring the change in the tumor volume) was investigated using a breast cancer (4T1) tumor-bearing mouse model. In addition, the systemic toxicity of co-administration of tLyP-1 with PGG-PTX was assessed by monitoring the change in the animal body weight. RESULTS: It was observed that co-administration of tLyP-1 with PGG-PTX dramatically improved PGG-PTX accumulation in the tumors, resulting in improved inhibition efficiency against tumor growth. Moreover, co-administration of tLyP-1 with PGG-PTX did not change the systemic toxicity profile of PGG-PTX. CONCLUSION: Co-administration of tLyp-1 may be a promising strategy for improving the passive tumortargeting performance of polymeric drug conjugates.

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.

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.