Mesoporous silica nanoparticles as a new carrier methodology in the controlled release of the active components in a polypill

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• 作者：Antonio L. Doadrio^a ; ^{antoniov@ucm.es} ; José ; M. Sá ; nchez-Montero^b ; Juan C. Doadrio^a ; Antonio J. Salinas^a ; ^c ; Marí ; a Vallet-Regí ; ^a ; ^c ; ^{vallet@ucm.es}
• 关键词：MSN ; mesoporous silica nanoparticles ; MSN-41 ; mesoporous silica nanoparticles with MCM-41 structure ; MCM-41 ; Mobil composition of matter #41 ; MCM-41s ; Mobil composition of matter #41 simplified molecular model ; CVDs ; cardiovascular diseases ; ESC ; European Society of Cardiology ; HTZ ; hydrochlorothiazide ; AML ; amlodipine ; LS ; losartan ; SV ; simvastatin ; EtOH ; ethanol ; BET ; Brunauer ; Emmett and Teller method ; BJH ; Barrett-Joyner-Halenda equation ; PSA ; polar surface area ; DM ; dipole moment ; ADME ; abs
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：97
• 期：Complete
• 页码：1-8
• 全文大小：1152 K
• 卷排序：97

文摘

Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based on mesoporous silica nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behavior when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment.