Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption.

SBA-15 mesoporous silica (MPS) has been widely used in oral drug delivery; however, it has not been utilized for solidifying lipid-based formulations, and the impact of their characteristic intrawall microporosity remains largely unexplored. Here, we derive the impact of the MPS microporosity on the in vitro solubilization and in vivo oral pharmacokinetics of the prostate cancer drug abiraterone acetate (AbA) when coencapsulated along with medium chain lipids into the pores. AbA in lipid (at 80% equilibrium solubility) was imbibed within a range of MPS particles (with comparable morphology and mesoporous structure but contrasting microporosity ranging from 0-247 m2/g), and their solid-state properties were characterized. Drug solubilization studies during in vitro lipolysis revealed that microporosity was the key factor in facilitating AbA solubilization by increasing the surface area available for drug-lipid diffusion. Interestingly, microporosity hindered hydrolysis of AbA to its active metabolite, abiraterone (Ab), under simulated intestinal conditions. This unique relationship between microporosity and AbA/Ab aqueous solubilization behavior was hypothesized to have significant implications on the subsequent bioavailability of the active metabolite. In vivo oral pharmacokinetics studies in male Sprague-Dawley rats revealed that MPS with moderate microporosity attained the highest relative bioavailability, while poor in vitro-in vivo correlations (IVIVC) existed between in vitro drug solubilization during lipolysis and in vivo AUC. Despite this, a reasonable IVIVC was established between the in vitro solubilization and in vivoCmax, providing evidence for an association between silica microporosity and oral drug absorption.

Porous Nanostructure, Lipid Composition, and Degree of Drug Supersaturation Modulate In Vitro Fenofibrate Solubilization in Silica-Lipid Hybrids.

The unique nanostructured matrix obtained by silica-lipid hybrids (SLHs) is well known to improve the dissolution, absorption, and bioavailability of poorly water-soluble drugs (PWSDs). The aim of this study was to investigate the impact of: (i) drug load: 3-22.7% w/w, (ii) lipid type: medium-chain triglyceride (Captex 300) and mono and diester of caprylic acid (Capmul PG8), and (iii) silica nanostructure: spray dried fumed silica (FS) and mesoporous silica (MPS), on the in vitro dissolution, solubilization, and solid-state stability of the model drug fenofibrate (FEN). Greater FEN crystallinity was detected at higher drug loads and within the MPS formulations. Furthermore, an increased rate and extent of dissolution was achieved by FS formulations when compared to crystalline FEN (5-10-fold), a commercial product; APO-fenofibrate (2.4-4-fold) and corresponding MPS formulations (2-4-fold). Precipitation of FEN during in vitro lipolysis restricted data interpretation, however a synergistic effect between MPS and Captex 300 in enhancing FEN aqueous solubilization was attained. It was concluded that a balance between in vitro performance and drug loading is key, and the optimum drug load was determined to be between 7-16% w/w, which corresponds to (200-400% equilibrium solubility in lipid Seq). This study provides valuable insight into the impact of key characteristics of SLHs, in constructing optimized solid-state lipid-based formulations for the oral delivery of PWSDs.

Metagenomic analysis of microbial community associated with coral mucus from the Gulf of Aqaba.

Coral-associated microbial communities contribute to a wide variety of useful roles regarding the their host, and therefore, the arrangement of the general microbiome network can emphatically impact coral wellbeing and survival. Various pollution sources can interfere and disrupt the microbial relationship with corals. Here, we adopted the bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP®) technique to investigate the shift of microbial communities associated with the mucus of the coral Stylophora pistillata collected from five sites (Marine Science Station, Industrial Complex, Oil Terminal, Public Beach, and Phosphate Port) along the Gulf of Aqaba (Red Sea). Our results revealed a high diversity in bacterial populations associated with coral mucus. Proteobacteria were observed to be the dominating phylum among all sampling sites. The identified bacterial taxa belong to the pathogenic bacteria from the genus Vibrio was presented in varying abundances at all sampling sites. Diversity and similarity analysis of microbial communists based on rarefaction curve and UniFrac cluster respectively demonstrated that there are variances in microbial groups associated with coral mucus along sites. The pollution sources among different locations along the Gulf of Aqaba seem to affect the coral-associated holobiont leading to changes in bacterial populations due to increasing human activities.