doctoralThesis
Síntese e caracterização de nanopartículas de sílicas obtidas a partir da perlita expandida para aplicação na liberação pH-responsiva de fármacos
Fecha
2019-06-28Registro en:
ALMEIDA, Janiele Mayara Ferreira de. Síntese e caracterização de nanopartículas de sílicas obtidas a partir da perlita expandida para aplicação na liberação pH-responsiva de fármacos. 2019. 160f. Tese (Doutorado em Química) - Centro de Ciências Exatas e da Terra, Universidade Federal do Rio Grande do Norte, Natal, 2019.
Autor
Almeida, Janiele Mayara Ferreira de
Resumen
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.