Formulation and In Vivo Studies of Solid Lipid Nanoparticles of Bortezomib

Bortezomib is formulated as the solid lipid nanoparticle (SLN) system with the use of a 3-factor, 3-level Box–Behnken design, by hot homogenization followed by an ultra sonication method. Trimyristin (Dynasan-114), tripalmitin (Dynasan116) and tristearin (Dynasan-118) were used as lipids and based on the results from the initial studies tripalmitin (Dynasan116) was selected as the lipid for the further studies along with phosphate dylcholine as surfactant and Poloxamer 188 as stabilizer. The optimized formulation (F1) was obtained with minimum particle size (204 nm), maximum entrapment efficiency (70.24) and drug loading (21.24). In vitro release studies showed that maximum cumulative drug release was obtained for F1 (99.74%). The optimized formulation Bortezomib followed zero-order release kinetics with a strong correlation coefficient (R2= 0.9994). The pharmacokinetic studies in rabbits demonstrated that SLN formulation could be used for increasing the oral bioavailability of the drug for more than 2 fold when compared with pure drug. SLNs of Bortezomib were successfully developed to yield an optimized formulation with lowest particle size and highest entrapment efficiency that could sustain the release of drug. Key words: Bortezomib, SLN, Cancer, Tripalmitin, Box-Behnken design, Pharmacokinetic studies.