title: Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan.
abstract: The aim was to improve the oral bioavailability and antihypertensive activity of poorly soluble drug valsartan (VAL) by modifying the design and delivery of mesoporous silica nanoparticles (MSNs). The synthesized MSNs were functionalized with aminopropyl groups (AP-MSN) through postsynthesis and coated with pH sensitive polymer Eudragit L100-55 (AP-MSN-L100-55) for pH dependant sustain release of anionic VAL. MSNs were characterized by Brauner-Emmett-Teller (BET) surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope (FESEM), Powder X-Ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC). Functionalized MSNs showed highest entrapment efficiency (59.77%) due to strong ionic interaction with VAL. In vitro dissolution of M-MSN [MSN-VAL and AP-MSN-VAL-L100-55 mixed equally] at physiological conditions demonstrated immediate release (MSN-VAL fraction) followed by sustained release (AP-MSN-VAL-L100-55 fraction) of 96% VAL in 960min. The dramatic improvement in dissolution was attributed to the amorphization of crystalline VAL by MSNs as evidenced by DSC and PXRD studies. No noticeable cytotoxicity was observed for MSN, AP-MSN and AP-MSN-L100-55 in MTT assay. Pharmacokinetic study of M-MSN confirmed 1.82 fold increases in bioavailability compared to commercial Diovan tablet in fasted male rabbits. Blood pressure monitoring in rats showed that the morning dosing of Diovan tablet efficiently controlled BP for just over 360min whereas the effect of M-MSN lasted for >840min.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address: nikhil_ju05@yahoo.co.in.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Biswas
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006863:Hydrogen-Ion Concentration; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D016062:Porosity; D011817:Rabbits; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D000068756:Valsartan / Q000737:chemistry* / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000180:Acrylic Resins; D000959:Antihypertensive Agents; D004337:Drug Carriers; C446821:Eudragit L100-55; D014867:Water; D012822:Silicon Dioxide; D000068756:Valsartan
keywords: Antihypertensive activity; Bioavailability; Functionalization; In vitro in vivo correlation; Mesoporous silica nanoparticles; Poorly water soluble drug