Mesoporous silica nanoparticles as a new carrier methodology in the controlled release of the active components in a polypill.
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.
Departamento de Química Inorgánica y Bioinorgánica, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Madrid, Spain. Electronic address: antoniov@ucm.es.
Antonio L
AL
Doadrio
Departamento de Química Orgánica y Farmacéutica, Grupo de Biotransformaciones, Universidad Complutense de Madrid, Spain.
José M
JM
Sánchez-Montero
Departamento de Química Inorgánica y Bioinorgánica, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Madrid, Spain.
Juan C
JC
Doadrio
Departamento de Química Inorgánica y Bioinorgánica, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
Antonio J
AJ
Salinas
Departamento de Química Inorgánica y Bioinorgánica, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital, 12 de Octubre i+12, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. Electronic address: vallet@ucm.es.
María
M
Vallet-Regí
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry*; D001241:Aspirin / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004338:Drug Combinations; D065546:Drug Liberation / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D008958:Models, Molecular; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry*
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C509968:MCM-41; D012822:Silicon Dioxide; D001241:Aspirin
Amlodipine besylate (PubChem CID: 60496); Antihypertensive drugs; Cholesterol lowering; Diuretic; Hydrochlorothiazide (PubChem CID: 3639); Losartan potassium (PubChem CID: 11751549); MCM-41 nanoparticles; Polypill; Simvastatin (PubChem CID: 54454)