Oral Delivery of ß-lactamase (BLM) by Self Nano-emulsion Drug Delivery System
Jun Shao, Department of Pharmacy and Administrative Sciences, College of Pharmacy and Health Sciences
Sripriya Venkata Ramana Rao, Payal Agarwal, Kavya Yajurvedi, Biotechnology and Drug Delivery Laboratory
To use self-nanoemulsion drug delivery system (SNEDDS) to deliver hydrophilic proteins orally.
ß-lactamase (BLM), a model a 29K Da protein, was formulated into a SNEDDS through a solid dispersion technique. The transport of BLM was studied with MDCK monolayers in vitro. The oral absorption of BLM in rats when delivered by such a SNEDDS was investigated. Then in-vitro and in-vivo correlation (IVIVC) was conducted.
The transport of BLM in SNEDDS was 100-fold higher than that by the solution form across MDCK monolayer, respectively. The estimated relative oral bioavailability of BLM when delivered by SNEDDS and by free solution was 6.34% and 2.4% respectively. The Cmax was 1.90 ± 0.09 mU/ml and the mean resident time (MRT) was 12.12 ± 4.97 hours for the SNEDDS formulation which was 2.7 fold and 1.3 fold higher than free solution respectively. The results demonstrate that the self nanoemulsion formulation increased BLM oral bioavailability by 2.5 fold (p<0.01) as compared to the free solution form. The regression plot of IVIVC was found to have an R2 value of 0.989.
A SNEDDS developed for BLM could significantly increase the transport of BLM across cell monolayer in vitro. SNEDDS is more efficient in delivering BLM orally compared to free solution in rats. Excellent IVIVC was obtained. SNEDDS system may be a potential system for non-invasive delivery of protein drugs.