Spray-Dried Rosuvastatin Nanoparticles for Promoting Hair Growth
AAPS PHARMSCITECH
Authors: Maged, Amr; Mahmoud, Azza A.; Salah, Salwa; Abd-elmonsif, Nehad M.; Ghorab, Mahmoud M.
Abstract
In this research, we examined the effect of rosuvastatin calcium-loaded nanoparticles on the hair growth-promoting activity on Albino rats. Nanoparticles were prepared using 2:1 weight ratio of drug to methyl-beta-cyclodextrin with 10, 20, and 30% stabilizers (phospholipid, polyvinyl pyrrolidone K30, and Compritol 888 ATO) using nanospray dryer. Subsequently, the prepared nanoparticles were evaluated for their process yield, particle size, polydispersity index, zeta potential, andin vitrodrug release as well asin vivostudies. The dried nanoparticles showed process yield values up to 84% with particle size values ranging from 218 to 6258 nm, polydispersity index values ranging from 0.32 to 0.99, and zeta potential values ranging from - 6.1 to - 11.9 mV. Combination of methyl-beta-cyclodextrin with 10% polyvinyl pyrrolidone K30 accomplished nanoparticles with the lowest particle size (218 nm) and polydispersity index (0.32) values. These nanoparticles had suitable process yield value (70.5%) and were able to retard drug release. The hair growth-promoting activity for the selected nanoparticles revealed the highest hair length values in Albino rats after 14 days of the hair growth study compared with non-medicated nanoparticles, nanoparticles' physical mixture, rosuvastatin solution, and marketed minoxidil preparation groups as well as the control group. The immunohistochemistry images for both selected nanoparticles and marketed minoxidil groups showed a significant increase in the diameter of hair follicle and percent area fraction of cytokeratin 19 in the outer root sheath of hair follicle compared with other tested groups. Rosuvastatin nanoparticles prepared by nanospray drying technique could be a good competitor to minoxidil for hair growth-promoting activity.
miR-18a activates Wnt pathway in ER-positive breast cancer and is associated with poor prognosis
CANCER MEDICINE
Authors: Nair, Madhumathy G.; Prabhu, Jyothi S.; Korlimarla, Aruna; Rajarajan, Savitha; Hari, P. S.; Kaul, Roma; Alexander, Annie; Raghavan, Rohini; Srinath, B. S.; Sridhar, T. S.
Abstract
Despite the established benefits of long-term endocrine therapy, women with hormone receptor-positive breast cancer remain at risk for late relapse. The basis of this is multi-factorial including genetic, epigenetic, and host factors. In this study we have explored the epigenetic regulation of estrogen receptor (ER)-dependent molecular and cellular phenotype by hsa-miR-18a-5p using well-established human ER-positive (ER+) breast cancer cell lines. miR-18a was overexpressed in MCF7 and ZR-75-1 and this led to an increase in the proliferative ability of the cells and concurrently resulted in decreased expression of luminal markers and higher expression of the basal marker, cytokeratin 14. The cells became more migratory with a significant repression of E-cadherin and activation of the Wnt noncanonical pathway. We observed an activation of the planar cell polarity (PCP) pathway with increased activation of JNK pathway and eventually change in actin dynamics. There was increased F-actin polymerization in cells with higher expression of miR-18a. Examination of miR-18a expression in a set of human ER+ breast cancer specimens showed a negative correlation between miR-18a andESR1transcripts as well as ER protein. Kaplan-Meier survival analysis of the cohort stratified by tumor hsa-miR-18a-5p levels produced significant differences in disease-free survival (log rankP < .05). This observation was independently validated in the METABRIC cohort. These data provide support for a role of hsa-miR-18a-5p in altering the proliferative and migratory behavior of ER+ cells and its potential utility as a prognostic marker in clinical ER+ breast cancers.