The pharmaceutical industry uses polymers as nanoparticles in controlled release formulations and
vector for having low cost compared to other methods of preparation of pharmaceutical dosage forms,
apparently not being recognized by the body's defense system, provide improved efficacy, reduce
toxicity and the dose of administered drug. The sulfate of chondroitin-co-N-isopropylacrylamide (SCM
+ NIPAAm) is a copolymer proposed for this purpose, from a synthetic polymer reaction, poly Nisopropylacrylamide
(PNIPAAm) with thermosensitive characteristics with a natural, Chondroitin
sulfate (CS), with bioadhesive characteristics. Thus, the copolymerization may be able to add these
properties and to improve its use as a vehicle for controlled-release. This study aimed to characterize
physico-chemical of sulfate chondroitin particles and N-isopropylacrylamide and SCM+NIPAAm
copolymer (2.5% and 5%) and SCM+PNIPAAm 2.5% and a partial toxicological evaluation of one of
these copolymers presenting the best properties of an efficient carrier of drugs, selected from the trials
of physic-chemical characterization. To determine the chemical structure of the particulate systems
and analyze the chemical components, it was performed Nuclear Magnetic Resonance Spectroscopy
(RMN) and Infrared Fourier Transformed Spectroscopy (FTIR), to analyze the morphology of the
particles, it was used Electron Microscopy (SEM), The Thermogravimetry and Differential Thermal
Analysis (TG/DTA) was used to evaluate the thermal behavior of particulate systems, as well as assist
in the analysis of kinetics of degradation (CD, Flynn-Wall-Ozawa method); it was also made in vitro
degradation technique and surface charge determining and particles size (Zeta potential analysis, PZ).
To evaluate the toxicity, it was performed bioassay in Artemia salina (24 and 48 hours), cell viability
(cytotoxicity) on PC-12 cells (MTT method), and also acute oral toxicity in mice. The NMR, FTIR and
SEM analysis showed similarity regarding the structural and morphologic aspects between the studied
copolymers. TG analyzes showed that SCM+NIPAAm 5% showed higher thermal stability compared
to the other copolymers evaluated, since its polymer decomposition occurs at temperatures above
around 233 °C. DTA demonstrated temperature values consistent with decomposition thermal events
provided by the curves of TG analysis. The stability was confirmed by CD and in vitro degradation
study, presenting, respectively, Ea> 100 kJ mol-1 and 48% of its initial weight after three months.
Furthermore, SCM+NIPAAm 5% presented particle diameter of less than 200 nm and polydispersity
index of 0.35, and the PZ> -30mV, characteristics of a promising candidate as a drug carrier.
Regarding toxicological evaluations, SCM+NIPAAm 5% did not show toxicity on bioassay A. saline
(LC50> 1000) and in the cellular model evaluated within the concentrations and circumstances of
exposure studied. The SCM+NIPAAm 5%, in the oral dose of 2000 mg/kg, did not show any obvious
sign of toxicity in mice, which was confirmed by the absence of anatomical and histopathological
changes. The copolymerization of chondroitin sulfate and N-isopropylacrylamide in the studied
concentration, given its physical-chemical characteristics and toxicological preliminary, presents
properties that contribute to propose a system which is a new form of controlled release, especially
drugs.
|
