Síntese e caracterização de nanopartículas de sílicas obtidas a partir da perlita expandida para aplicação na liberação pH-responsiva de fármacos

Abstract

pH-dependent or pH-responsive drug delivery systems are capable of promoting the release of drugs in a modified manner or at specific locations. Silica nanoparticles (NPS) are excellent materials for application as release systems, since their surface has abundance in silanols (Si-OH) groups, which are highly sensitive to variations in pH. Drug delivery systems are very important for aiding and improving the treatment of chronic diseases or long periods of drug treatment. Tuberculosis is considered by the WHO as a neglected, serious and lethal disease. Isoniazid (INH) is one of the first-line antibiotics for long periods of tuberculosis treatment. Part of INH degrades in very acidic media such as stomach pH, impairing the treatment of tuberculosis and requiring high daily doses to the patient to maintain the therapeutic effect. Topiramate (TPM) is a potent antiepileptic, used in high daily dosages since it has low bioavailability. In this context, NPS were used as inorganic matrices for the transport of TPM and INH in release studies, in vitro. The synthesis of NPS was made using a natural source of silica as a precursor (the expanded perlite, which consists of an abundant, natural, low-cost aluminosilicate) by a fast, simple method without many apparatuses. The synthesis parameters by Stöber method (sol-gel process) were varied, obtaining particles of different sizes and distribution (monomodal and bimodal). The NPS were characterized by XRD, FTIR, SEM, DLS (particle size, 173.8 to 559.1 nm) and negative zeta potential over a wide pH range. An amorphous structure and spherical morphology were observed. A methodology for the detection and quantification of TPM by GC-MS was developed, replacing the standard HPLC-MS technique. The drugs were incorporated in the NPS under optimized conditions by experimental design (factorial, 2n ) by different methods: INH by adsorption and melt-loading TPM. The drug release study was done using dissolution media simulating the gastrointestinal pH: pH 1.2 (stomach), pH 6.8 and 7.4 (intestine). The duration of the assay also followed the estimated time of gastrointestinal transit an oral solid dosage form faces when ingested (2 h for pH 1.2 and 6.8 and 4 h for pH 7.4). The incorporation of the TPM brought a new methodology for the preparation of carriers (NPS/TPM) using a controlled temperature system of a thermobalance (Thermogravimetry -TG), with several advantages over other heating methods. The incorporation efficiency was 5.14 mg/g for INH and 1.0 mg/mg for TPM, evaluated by FTIR and XRD. The release study showed that NPS presented adequate sizes for their use as INH and TPM nanocarriers, presenting a pH-responsive surface with high potential for controlled release (8 hours for INH and 5 hours for TPM), offering a higher absorption in pH that simulates the intestinal environment (pH 7.4) and guarantees a lower acid (stomach) degradability, as in the case of INH. The kinetic study evaluated the zero order, first order and Higuchi models for drug release in NPS, and the zero order model presented the best fit, indicating that INH and TPM were released in a pH-responsive manner and of NPS.