Search results for "Polymer therapeutics"
showing 8 items of 8 documents
Well-defined polypeptide-based systems as non-viral vectors for cytosolic delivery
2017
A convenient cytosolic drug delivery constitutes a very powerful tool for the treatment and/or prevention of several relevant human diseases. Along with recent advances in therapeutic technologies based on biomacromolecules (e.g. oligonucleotides or proteins), we also require the development of technologies which improve the transport of therapeutic molecules to the cell of choice. This has led to the emergence of a variety of promising methods over the last 20 years. Despite significant progress, these methods still suffer from several shortcomings including low/variable delivery efficiency, high cytotoxicity, and perhaps most importantly, ineffective endosomal/lysosomal escape. In this co…
Multifunctional Poly(ethylene glycol)s
2011
In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…
Polymer Drug Conjugates for the Treatment of Neurodegenerative Disorders
2013
Nanociencia y nanotecnología son la base de técnicas innovadoras para el transporte de fármacos con beneficios potenciales para el paciente y nuevos mercados para la industria. La obtención de nuevos sistemas de transporte de fármacos más efectivos es uno de los principales retos actuales, junto con la mejora del diagnóstico tanto in vitro como in vivo y el desarrollo de tecnologías para la ingeniería tisular y la medicina regenerativa. Además de ser necesario disponer de moléculas con actividad farmacológica para conseguir terapias efectivas se necesitan su transporte y liberación controlada para llegar a conseguir tratamientos con mayor índice terapéutico. El uso de estrategias de direcci…
Polymer-drug conjugates as platforms for combination therapy in the treatment of hormone-dependent breast cancer
2013
1. Objetivos de la Investigación. Los conjugados poliméricos son nanoconstrucciones multicomponente presentes actualmente en clínica como terapia anticancerígena, tanto como agentes únicos, como formando parte de combinaciones. Estos nanoconjugados tienen el potencial de mejorar farmacológicamente el tratamiento de tumores sólidos, debido a una acumulación pasiva en el tumor (efecto ‘EPR’) y a un diferente mecanismo de internalización celular y posterior liberación del fármaco(s). La transferencia de conjugados polímero-proteína a uso clínico rutinario, y el desarrollo clínico de conjugados polímero-fármaco anticancerígeno sitúa a los conjugados poliméricos como una de las primeras clases d…
SYNTHESIS, PHYSICO-CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF A PACLITAXEL MACROMOLECULAR PRODRUG
2004
Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a hig…
Development of polypeptide-based therapeutics for topical delivery
2019
Topical administration represents the main route to attain local therapeutic activity of bioactive agents in several organs, such as the skin or the heart by means of devices that enhance drug transport through the endothelium acting as a reservoir. The complex structure of the skin protects the human body against potentially harmful external agents; however, this protective mechanism inhibits the penetration of topically administering bioactive agents employed for the treatment of skin diseases. Unfortunately, many of the topical drugs currently used or under evaluation in clinical trials lack the appropriate physico-chemical characteristics required for delivery through the skin. However,…
Polymer-doxycycline conjugates as fibril disrupters: an approach towards the treatment of a rare amyloidotic disease.
2014
The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease…
Glycosylated macromolecular conjugates of antiviral drugs with a polyaspartamide.
2004
Two new polymeric conjugates for specific liver targeting were prepared by conjugation of sugar moieties and antiviral drugs to alpha, beta-poly[N-2-(hydroxyethyl)-DL-aspartamide] (PHEA). PHEA-galactopyranosylphenylthiocarbamide-mono-O-succinylganciclovir (conjugate 7) and PHEA-mannopyranosylphenylthiocarbamide-O-succinylacyclovir (conjugate 8) were synthesized according to a multi-step procedure which allowed for obtaining high product yield and process standardization. Conjugate 7 contained 7.5 and 8.5% of galactose and ganciclovir (substituent/repeating unit, mol/mol), respectively, and conjugate 8 contained 14.2 and 10.8% of mannose and acyclovir, respectively. In vitro studies demonstr…