Contents lists available at ScienceDirect European Journal of Pharmaceutical Sciences journal homepage: www.elsevier.com/locate/ejps Prolonged release of metformin by SiO 2 nanoparticles pellets for type II diabetes control Rosalba Patiño-Herrera a, ⁎ , José Francisco Louvier-Hernández a , Eleazar M. Escamilla-Silva a , Julie Chaumel b , Alma Gabriela Palestino Escobedo b , Elías Pérez c a Departamento de Ingeniería Química, Tecnológico Nacional de México/Instituto Tecnológico de Celaya, Av. Tecnológico y Antonio García Cubas No. 600 Pte., Celaya, Guanajuato 38010, Mexico b Facultad de Ingeniería Química, UASLP, Álvaro Obregón 64, San Luis Potosí, S.L.P. 78000, Mexico c Instituto de Física, UASLP, Álvaro Obregón 64, San Luis Potosí, S.L.P. 78000, Mexico ARTICLE INFO Keywords: Mesoporous silica nanoparticles Metformin Pellet Drug delivery system Drug release Diabetes mellitus ABSTRACT Mesoporous silica nanoparticles (MSNPs) were synthesized and loaded with metformin hydrochloride (Metf), its adsorption has studied at different concentrations and pHs, optimal adsorption conditions were determined. Hybrid MSNPs-Metf were mixed with chitosan to compress them and form quasi-spherical pellets, were coated with five chitosan layers as a barrier to prolong metformin release. It showed that this pellet is useful for metformin controlled release since drug over time was significantly delayed by the chitosan coating and then, as metformin is electrostatically linked to MSNPs, it also controls the release of drug, releasing 170 mg after 17 h of exposure at pH 1.2. When pH is > 1.2, metformin release was significantly prolonged. Since 170 mg is 21% of a 850-mg metformin dose and previous studies report that 90% of metformin is recovered as unchanged drug in urine after 12 h of metformin intakes. These results suggest that MSNPs-Metf pellets, coated with chitosan, are an option to avoid excessive metformin ingest. 1. Introduction Diabetes mellitus is a global health problem due to its elevated pre- valence and disability produced. It is one of the main morbidity and mortality cause; nearly 8.3% of the world's population suffers from this disease, its origin lies in some factors such as obesity and sedentary lifestyle (Wild et al., 2004). Diabetes mellitus developing serious diseases affecting heart, blood vessels, teeth, kidneys, eyes, nerves and devel- oping infections, which shortens life expectancy (Chacko, 2016), it is caused by a multifarious metabolic disorder characterized by defects in insulin secretion and/or the insulin action, causing hyperglycemia, where fasting plasma glucose concentration is above 1.26 g/L or above 2.00 g/L in blood at any time (Viswanatha et al., 2017). Metformin hydrochloride (Metf) is one of the most widely used agents for Diabetes mellitus control, it is an oral antihyperglycemic that improves glucose tolerance in patients by decreasing basal and post- prandial plasma glucose. Metformin acts through three mechanisms: first, reduces hepatic glucose production by inhibiting hypoglycemia and avoids hyperinsulinemia; second, it increases insulin sensitivity in muscle and improves peripheral glucose uptake and utilization; third, it delays the intestinal absorption of glucose. During controlled clinical trials of metformin (850 mg) three times daily, peak plasma levels are reached between 2.5 and 3.0 h after ingestion and do not exceed 590–1300 ng/mL with half-life between 1.5 and 4.5 h, reaching a lower concentration in blood than in plasma (Moffat et al., 2006). Metformin kinetics are characterized by slow and incomplete absorption (bioa- vailability 50–60%), from an oral dose of about 30 to 50% is excreted unchanged in urine within 24 h and about 30% in feces (Moffat et al., 2006). Traditional doses to eliminate pain or infections require high med- ication levels, generating toxicity, to keep low drug level in serum lower levels than the required dose are provided, causing drug re- sistance. A local system that delivers medicament could correct these inconvenient of traditional dosing (Warren et al., 2008). A problem is presented when drugs are ingested orally, they could dissolve rapidly in the stomach producing blood level peaks and may not produce ade- quate levels. In addition, when drug blood level is adequate, it begin to decrease and becomes necessary to ingest another dose in a few hours. It is a problem since some drugs are irritating to the stomach or may produce undesirable side effects. The need to release drugs in a gradual or sustained way has given rise to exhaustive research that has gener- ated different solutions, among them arise the possibility of coating the https://doi.org/10.1016/j.ejps.2019.02.003 Received 24 August 2018; Received in revised form 6 December 2018; Accepted 3 February 2019 ⁎ Corresponding author. E-mail address: roos_ph@iqcelaya.itc.mx (R. Patiño-Herrera). European Journal of Pharmaceutical Sciences 131 (2019) 1–8 Available online 06 February 2019 0928-0987/ © 2019 Elsevier B.V. All rights reserved. T