RESUMEN
Polymers are extensively used for the realization of drug delivery systems across multiple scales, from nanomedicines to microparticles and macroscopic implantable devices, for their favorable biodegradation profiles and tunable physicochemical features. The accurate quantification of the polymer content is key to finely controlling drug loading and release and ensuring reproducibility, yet it continues to be a major challenge in the design and development of delivery systems. In this study, we introduce a novel protocol based on the PULCON technique to quantify, with a routine NMR spectroscopy analysis, the precise concentration of polymers in various delivery systems. Specifically, the PULCON protocol is applied to characterize the physicochemical and pharmaceutical properties of nanoparticles, microparticles, and implantable devices realized by combining three extensively used polymers, namely, poly(lactic-co-glycolic acid) (PLGA), poly(vinyl alcohol) (PVA), and poly(ethylene glycol) (PEG). Without using internal calibration procedures, in a single step, the PULCON protocol precisely quantifies the concentration of each polymer and the drug content. This approach can be readily implemented on standard NMR spectrometers, enabling accurate characterization of drug delivery systems and facilitating their effective development.
Asunto(s)
Sistemas de Liberación de Medicamentos , Espectroscopía de Resonancia Magnética , Polietilenglicoles , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Espectroscopía de Resonancia Magnética/métodos , Sistemas de Liberación de Medicamentos/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Polietilenglicoles/química , Alcohol Polivinílico/química , Polímeros/química , Nanopartículas/química , Liberación de Fármacos , Portadores de Fármacos/química , Tamaño de la PartículaRESUMEN
Malignancies of the lungs, both primary and metastatic, are the leading cause of death worldwide. Over 1.5 million new cases of primary lung cancer are diagnosed annually worldwide with a dismal five-year survival rate of approximately 15%, which remains unchanged despite major efforts and medical advances. As expected, survival for patients with lung metastases is even worse at about 5%. Early detection and staging are fundamental in improving survival rates and selecting the most effective treatment strategies. Recently, nanoparticles have been developed for imaging and treating various cancers, including pulmonary malignancies. In this work, three different examples of nanoparticle configurations for cancer theranosis are presented, namely conventional spherical polymeric nanoparticles with a diameter of ~ 150 nm; and discoidal mesoporous silicon nanoconstructs and discoidal polymeric nanoconstructs with a diameter of ~ 1,000 nm and a height of 400 and 500 nm, respectively. The spherical nanoparticles accumulate in tumors by means of the well-known enhanced permeation and retention effect, whereas sub-micrometer discoidal nanoconstructs are rationally designed to adhere firmly to the tortuous tumor vasculature. All three nanoparticles are characterized for their in vivo performance in terms of magnetic resonance, positron-emission tomography (PET), and optical imaging. Preliminary data on the in vivo and ex vivo PET/CT imaging of breast cancer metastasis in the lungs using discoidal nanoconstructs is presented. In conclusion, opportunities for nanoparticle-based theranosis in primary lung cancer and pulmonary metastasis are presented and discussed.
