Biomimetic Synthesis and Evaluation of Interconnected Bimodal Mesostructured MSF@Poly(Ethyleneimine)s for Improved Drug Loading and Oral Adsorption of the Poorly Water-Soluble Drug, Ibuprofen

PURPOSE: The aim of this study was to improve the oral bioavailability and anti-inflammatory activity of the poorly soluble drug ibuprofen (IBU) by employing a new kind of poly(ethyleneimine)s (PEIs)-based mesocellular siliceous foam (MSF) called B-BMSF@PEI as drug carrier. METHODS: B-BMSF@PEI was biomimetically synthesized by using PEIs as templates, catalysts and scaffolds under ambient conditions, and the structural characteristics, including size, morphology, mesoscopic structure and pore properties, were estimated by TEM, SEM, FTIR and N(2) desorption/adsorption measurement. Then, IBU was incorporated into B-BMSF@PEI at the drug:carrier weight ratio of 1:1. The structural features of IBU before and after drug loading were systemically characterized. IBU and B-BMSF@PEI were then subject to in vitro drug release study and wettability analysis. Finally, in vivo pharmacokinetics and anti-inflammatory pharmacodynamics studies were carried out to evaluate the efficacy of B-BMSF@PEI on improving the oral adsorption of IBU. RESULTS: The results demonstrated that B-BMSF@PEI was a meso–meso porous silica material with foam appearance. It consisted of uniform spherical cells (40 nm) with interconnected pore networks. IBU can be successfully loaded into B-BMSF@PEI with high efficiency (as high as 39.53%), and crystal IBU was effectively converted to an amorphous state during this process. Benefiting from the great architectures of B-BMSF@PEI, IBU/B-BMSF@PEI performed good wetting property and significantly improved the dissolution rate in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Notably, IBU exhibited very satisfactory relative bioavailability (681.4%) and anti-inflammatory effects (the inhibition rates were between the ranges of 113.5% to 1504.3%). CONCLUSION: B-BMSF@PEI with bimodal mesoporous system and interconnected nanopores was obtained owing to the dynamic self-assembly functions of PEIs. It had superiority in drug loading and could improve the oral adsorption of ibuprofen to a satisfactory level.