Do the lichens Xanthoparmelia conspersa (Ach.) Hale and Rhizocarpon Ram. Em. Th. Fr. subgenus Rhizocarpon utilise exogenous carbohydrates for radial growth?

To field test the hypothesis that lichen thalli can use environmental sources of carbon, solutions of ribitol, arabitol and mannitol were added to intact thalli of Xanthoparmelia conspersa (Ach.) Hale and a yellow species of Rhizocarpon (Rhizocarpon Ram. Em. Th. Fr. subgenus Rhizocarpon). In addition, ribitol and an arabitol/mannitol mixture were added to the marginal hypothalli of Rhizocarpon thalli after removal of the areolae. Carbohydrates were added at the beginning of 2- or 3-month growth periods for up to 15 months at concentrations approximately three times the levels estimated to be in the thalli. Addition of carbohydrates to intact thalli of both species had no effect on total radial growth but addition of mannitol significantly increased growth of X. conspersa thalli in the September/October growth period in one experiment. However, this effect was not repeated in a subsequent experiment in which different concentrations of mannitol were added to intact thalli. Addition of ribitol to hypothalli of Rhizocarpon resulted in significantly increased growth in the first few months of the experiment, growth then declining to levels below that of untreated thalli. The data suggest that although hypothalli of Rhizocarpon may have the ability to utilise exogenous carbohydrates for growth, there was little evidence that intact thalli of either species utilise environmental sources of carbon in the field.

Precipitation casting of drug-loaded microporous PCL matrices:incorporation of progesterone by co-dissolution

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37°C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 μg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37°C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.

Progesterone release from a silicone intravaginal ring in pigtailed macaques

Background: Heterosexual HIV transmission continues to spread worldwide. Intravaginal rings (IVRs) formulated with antiretroviral drugs hold great promise for HIV prevention in women. IVRs provide the benefit of being coitally-independent and coitally-covert for an extended period. As a proof-of-concept, we tested the in vivo release of progesterone from a silicone elastomer vaginal ring device. Methods: Six female pig-tailed macaques were treated with a GnRH agonist (Lupron) prior to ring placement. Four macaques received a progesterone-loaded silicone ring, and two macaques received a blank silicone ring. Blood, vaginal swabs, CVL, and/or biopsies were collected during ring placement, and after ring removal. Results: The median plasma progesterone levels for macaques with a progesterone IVR were 13,973 pg/ml (day 3), 12,342 pg/ml (day 7), 10,112 pg/ml (day 14), 8445 pg/ml (day 21) and 8061 pg/ml (day 28), with a significant decrease from day 14 to day 21 (P = 0.0286). The median plasma progesterone levels for macaques with a blank IVR were 221±±± ±±88 pg/ml. Macaques with a progesterone IVR had CVL progesterone levels of 20,935 pg/ml (day 7), 6892 pg/ml (day 21) and 11,515 pg/ml (day 28). Macaques with a blank IVR had CVL progesterone levels of 29 �± 13 pg/ml. There were no disturbances to the normal vaginal microflora, and plasma and CVL cytokine analysis did not indicate a proinflammatory response due to ring placement. The vaginal biopsies did not display any pathology following ring removal. Overall, the IVRs were well tolerated without any indication of inflammation or significant changes in the vaginal compartment.