RESUMO
Aim: To characterize a molecularly imprinted polymer via precipitation polymerization for the extraction of cotinine in urine. Methods: The polymer was created via precipitation polymerization. Physical characteristics of the polymer were assessed via scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. The polymer adsorption capacity was assessed and an solid-phase extraction method from urine by LC-MS/MS was developed. Results: The polymer had small, spherical morphology and little thermal decomposition. The extraction method yielded cotinine recoveries of 77-103% in urine. The molecularly imprinted polymer adsorption capacity for cotinine was 448.2 ± 2.1 µg/mg. Common interferants did not affect cotinine's extraction. Conclusion: The resulting polymer was determined to be specific for cotinine and can be used for the detection of cotinine in urine for clinical samples.
Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Humanos , Cotinina , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem , Extração em Fase Sólida/métodos , Polímeros/química , AdsorçãoRESUMO
Gemcitabine (GMT) is a nucleoside analog used in the treatment of a variety of solid tumors. GMT was chemically modified with a hydrolysable linker, and subsequently incorporated into a poly(anhydride-ester) backbone via melt-polymerization, with the active antimetabolite GMT, thus, becoming the repeat unit that makes up this new material, a biodegradable polymer. Characterization of the structure of polymeric GMT (polyGMT) revealed the incorporation of an average 26 molecules of GMT per polymer chain, which corresponds to a drug loading of 58%w/w. The glass transition temperature of the formed polyGMT was determined to be 123 °C. PolyGMT was engineered into nanoparticles (NPs) using a dialysis-based method, with a resulting geometric diameter of 206 ± 38 nm. The particles are easily dispersible and stable in aqueous-based media, with a hydrodynamic diameter of 229 ± 28 nm. The prepared hydrolysable polyGMT NPs demonstrate ultra-long release profile due to the hydrophobic nature of the linker, and as per characteristic erosion behavior of polymers with anhydride-ester bonds. Accelerated in vitro release studies demonstrate the recovery of free GMT upon hydrolysis, with biological activity as assessed by cytotoxicity assays performed in adenocarcinoma human alveolar basal epithelial (A549) and highly metastatic murine osteosarcoma (K7M2) cells lines. The characteristics of polyGMT, including its thermal properties and built in hydrolysable structure, are thus conducive for use in the preparation of drug delivery systems. Engineered structures prepared with polyGMT can maintain their morphology at ambient and physiologically relevant conditions, and free GMT is recovered as the anhydride and ester bonds are hydrolyzed. This work is innovative as for the first time we demonstrate the ability to polymerize GMT in a hydrolysable polymer structure, and engineer NPs of this polymeric chemotherapy. The synthetic strategy allows for tuning of the polymer hydrophobicity and thus potentialize its behavior, including degradation profile, by varying the linker chemistry. Such controlled release hydrolysable polymers with very high drug loading and controlled erosion profiles are relevant as they may offer new opportunities in drug delivery applications for the treatment of malignant neoplasms.