Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation via Thiol-Maleimide Click Reaction for Intravesical Drug Delivery.

The development of nanocarriers to prolong the residence time and enhance the permeability of chemotherapeutic drugs on bladder mucosa is important in the postsurgery treatment of superficial bladder cancers (BCs). Here, the mucoadhesive HA-SH/PF127 nanogels composed of a temperature-sensitive Pluronic F127 (PF127) core and thiolated hyaluronic acid (HA-SH) shell were prepared by the emulsification/solvent evaporation method. The nanogels were constructed through the thiol-maleimide click reaction in the HA-SH aqueous side of the oil-water interface and self-oxidized cross-linking thiols between HA-SH. The HA-SH/PF127 nanogels prepared at different thiol-to-maleimide group molar ratios, water-to-oil volume ratios, and cross-linking reaction times were characterized regarding hydrodynamic diameter (Dh) and zeta potential (ζ), and the optimal formulation was obtained. The excellent mucoadhesive properties of the HA-SH/PF127 nanogels were evaluated by using the mucin particle method. Doxorubicin (DOX) was encapsulated in the PF127 core of DOX@HA-SH/PF127 nanogels with a high loading efficiency (87.5%) and sustained release from the nanogels in artificial urine. Ex vivo studies on porcine bladder mucosa showed that the DOX@HA-SH/PF127 nanogels enhanced the penetration of the DOX into the bladder mucosa without disrupting the mucus structure or the bladder tissue. A significant dose-dependent cytotoxic effect of DOX@HA-SH/PF127 nanogels on both T24 and MB49 cells was observed. The present study demonstrates that the mucoadhesive HA-SH/PF127 nanogels are a promising intravesical drug delivery system for superficial BC therapy.

[A prospective cohort study on human immunodeficiency virus and syphilis seroconversion among injecting drug users].

OBJECTIVE: To study the rate of human immunodeficiency virus (HIV) seroconversion, HIV transmission and related risk factors among injecting drug users (IDUs) in an area of Sichuan province. METHODS: In November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang county of Sichuan province, China. Follow-up visits were carried out every 6 months to study the situation of drug use, sexual behaviors of the IDUs and blood specimens were collected to test for antibodies against HIV and syphilis. RESULTS: During a 24-month follow-up period, cohort retention rate and HIV incidence were 75.7% and 2.53 per 100 person-years [95% confidence interval (CI): 1.10-3.97)], respectively. Multivariate Poisson regression model showed that risk factors which were significantly associated with HIV seroconversion would include: ethnicity (RR = 12.42; 95% CI: 2.72-56.74, P = 0.0012) and needle or syringe sharing in the past 3 months (RR = 4.06; 95% CI: 1.29-12.81, P = 0.0168). Syphilis seroconversion in this cohort was 4.71 per 100 person-years (95% CI: 2.59-6.82). In multivariate Poisson regression being female (RR = 4.42; 95% CI: 1.78-10.99, P = 0.0014) appeared to be the only factor which was significantly associated with syphilis seroconversion. CONCLUSION: Our study results showed that there was a rapid transmission of HIV and syphilis among IDUs in Sichuan province, suggesting that effective intervention should be urgently taken.

HIV incidence and factors contributed to retention in a 12-month follow-up study of injection drug users in Sichuan Province, China.

HIV-1 seroconversion and subtype were evaluated, and factors associated with cohort retention were analyzed for subjects' baseline sociodemographic and behavioral characteristics in a 12-month follow-up study of injection drug users (IDUs). In November 2002, a community-based baseline survey was conducted to recruit 333 HIV-seronegative IDUs for a prospective cohort study in Xichang County of Sichuan Province, China. During the 12-month follow-up period, HIV incidence was 3.17 per 100 person-years (95% confidence interval [CI]: 0.98, 5.37), and all subtypes of 8 HIV-1 seroconversions were CRF_07BC. The retention rate at the 12-month follow-up visit was 70.3% (234 of 333 subjects). In a multiple logistic regression model, ethnicity (OR = 0.60, 95% CI: 0.34, 1.04) and appearing at the 6-month follow-up visit (OR = 9.03, 95% CI: 5.14, 15.89) were independently associated with retention. No drug-using or sexual behaviors were found to be associated with retention. This study confirmed one of drug-trafficking routes in mainland China, from Yunnan to Sichuan and then to Xinjiang. This study also suggested that HIV is spreading rapidly to more geographic areas along drug-trafficking routes in China, and a short-term follow-up rate may predict a long-term retention rate in this IDU cohort.