In vivo evaluation of chitosan as an adjuvant in subcutaneous vaccine formulations

Vaccines utilising pure antigens instead of whole pathogens and alternative administration routes require the use of potent adjuvants and effective antigen delivery systems. Chitosan has been reported to act as both an adjuvant as well as a matrix for delivery systems. Chitosan is a natural product produced predominantly from crab shell and commercially available preparations vary in molecular weight, degree of deacetylation and purity. In this study, the impact of chitosan characteristics (molecular weight, degree of deacetylation, particle size, viscosity and impurities) on adjuvant activity were examined. It could be shown that the degree of immune response differed if different chitosan qualities were used and this could be attributed to different characteristics of the chitosan qualities: the immunoadjuvant effect of chitosan probably is a result of an interplay between chemical properties such as molecular weight and degree of deacetylation and physical properties such as particle size and preparation technique, which impacts characteristics such as solubility and viscosity. Hence, the chitosan quality to be used as adjuvant in vaccine preparations needs to be selected carefully.     

Favorable Mortality Profile of Naltrexone Implants for Opiate Addiction

ABSTRACT

Several reports express concern at the mortality associated with the use of oral naltrexone for opiate dependency. Registry controlled follow-up of patients treated with naltrexone implant and buprenorphine was performed. In the study, 255 naltrexone implant patients were followed for a mean (± standard deviation) of 5.22 ± 1.87 years and 2,518 buprenorphine patients were followed for a mean (± standard deviation) of 3.19 ± 1.61 years, accruing 1,332.22 and 8,030.02 patient-years of follow-up, respectively. The crude mortality rates were 3.00 and 5.35 per 1,000 patient-years, respectively, and the age standardized mortality rate ratio for naltrexone compared to buprenorphine was 0.676 (95% confidence interval = 0.014 to 1.338). Most sex, treatment group, and age comparisons significantly favored the naltrexone implant group. Mortality rates were shown to be comparable to, and intermediate between, published mortality rates of an age-standardized methadone treated cohort and the Australian population. These data suggest that the mortality rate from naltrexone implant is comparable to that of buprenorphine, methadone, and the Australian population.     

Increase in weight after treatment with depot neuroleptics.

A trial has been performed investigating changes in weight in 99 female patients who have been treated with clopenthixol decanoate or perpehnazine enanthate after prior treatment with different oral neuroleptics. We found a significantly higher mean weight after the oral treatment period and a slight, but not statistically significant, further weight increase after the following depot period. In addition the rate of increase in weight was significantly lower during the depot treatment period. These increases might be due to achievement of a steady-state in weight during the first treatment period with oral intake. We found no difference between clopenthixol decanoate and perphenazine enanthate as regards change in weight or rate of change in weight.     

Preparation of Three-Month Depot Injectable Microspheres of Leuprorelin Acetate Using Biodegradable Polymers

To obtain a three-month release injection of leuprorelin acetate, microspheres were prepared with copoly(DL-lactic/glycolic acid) or poly(DL-lactic acid) (PLA) using an in-water drying method, and drug release was evaluated. The content of water-soluble oligomers in the polymers was found to strongly affect the initial burst, and reducing the content to less than 0.1% was necessary to keep the first-day release below 10%. Drug loading of more than 15% also increased the initial drug release; the acceptable maximum loading was 12%. Elevation of the glass transition temperature of the microspheres was observed with an increase in drug loading. This suggests formation of a rigid structure, possibly with arrangement of the polymer around the drug cores like in a micelle. This structure provides a hydrophobic barrier against diffusion of the hydrophilic peptide, resulting in high trapping efficiency and long-term sustained release dependent on polymer erosion. The microspheres prepared with PLA having a m.w. of 12,000 to 18,000 provided linear sustained release and persistent serum levels of the drug in rats for over 3 months.     

Long-term results with a long-acting formulation of D-TRP-6 LH-RH in patients with prostate cancer: an Italian prostatic cancer project (P.O.N.CA.P.) study

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.     

那法瑞林埋植型长效制剂对大鼠子宫内膜异位的抑制作用

研究那法瑞林埋植型长效制剂单次应用对大鼠子宫内膜异位的作用及作用机制。采用手术方法建立大鼠模型,血清雌二醇（E2）、孕酮（Pg）水平和异位内膜雌激素受体（ER）、孕激素受体（PR）分别用酶免疫和亲和组化一步法检测。结果：那法瑞林长效制剂对异位内膜的抑制率（70．4±25．1）％接近去势组;血清E2和Pg的周期性分泌高峰消失;子宫和卵巢萎缩退化,重量减轻;异位内膜ER和PR阳性率也显著降低。结论：那法瑞林长效制剂对大鼠子宫内膜异位有显著抑制作用,低甾体激素水平是其主要作用机制。     

GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation

Objective: This study aims to explore the differences of the ovarian stimulation (OS) characteristics, laboratory, and clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol during controlled ovarian hyperstimulation (COH).

Methods: About 1883 consecutive IVF/ICSI fresh cycles of normal ovarian responders were retrospectively analyzed, with 1229 in the single-dose GnRH agonist protocol group and 654 in the GnRH antagonist protocol group at Reproductive Medical Center of Tongji Hospital from 1 January 2014 to 31 December 2017.

Results: The follicular-phase single-dose GnRH agonist group showed significantly more oocytes obtained, higher implantation rate and pregnancy rate, as well as lower luteinizing hormone (LH) level and estradiol (E2)/oocyte ratio on the day of human chorionic gonadotropin (hCG) administration. However, differences were not significant in meiosis II (MII) oocyte rate, two pronuclear zygote (2PN) embryo rate, viable embryo rate or high-quality embryo rate, compared with the GnRH antagonist group. Further comparison of clinical outcomes in the first frozen-thawed cycles did not show significant difference in either implantation or clinical pregnancy rate between the two protocol groups.

Conclusions: Follicular-phase single-dose GnRH agonist protocol may achieve better clinical outcomes in normal ovarian responders, which could be explained more by positive effect on endometrial receptivity rather than embryo quality.