Therapeutic nanoparticles from novel multiblock engineered polyesterurethanes (original) (raw)
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Polyurethane-based drug delivery systems
International Journal of Pharmaceutics, 2013
Polyurethanes (PUs) are formed by a reaction between isocyanates and diols to yield polymers with urethane bonds (-NH-COO-) in their main chain. A great variety of building blocks is commercially available that allows the chemical and physical properties of PUs to be tailored to their target applications, particularly for the biomedical and pharmaceutical fields. This article reviews the synthesis and characterization of PUs and PU-copolymers, as well as their in vitro and in vivo biodegradability and biocompatibility. Particular emphasis is placed on the use of PUs for the controlled release of drugs and for the (targeted) delivery of biotherapeutics.
Biostability and biological performance of a PDMS-based polyurethane for controlled drug release
Biomaterials, 2008
Polymers have been used to deliver therapeutic agents in a range of medical devices with drug eluting stents being the most widespread current application. Although polymers enable controlled release of a therapeutic agent, the polymeric surface has been reported to provide suboptimal biocompatibility and haemocompatibility and it has been suggested that currently used polymers may be at least partly responsible for the late adverse events observed in intravascular stent systems. In this study, the biostability and biological performance of a siloxane-based polyurethane elastomer (E2A) demonstrating excellent long-term biostability in the unloaded state was investigated following incorporation of a therapeutic agent. After implantation in an ovine model for 6 months, samples were assessed using SEM and ATR-FTIR to determine changes in the surface chemical structure and morphology of the materials and tensile testing was used to examine changes in bulk characteristics. Biological response was assessed using in vitro cytotoxicity testing and histological analysis. Results indicated that incorporation of 25 mg/g dexamethasone acetate (DexA) into the siloxane-based polyurethane resulted in no significant difference in the biostability and biocompatibility of the material. Some level of cytotoxic potential was exhibited which was believed to result from residual DexA leaching from samples during the extraction process. These findings suggest that E2A is a potential candidate for a delivery vehicle of therapeutic agents in implantable drug delivery applications.
Three polyether-ester triblock diols, with various molecular weights, were synthesized from ε-caprolactone and polyethylene glycol and used, with diisocyanates, as soft segments for the preparation of polyurethane acrylate oligomers. The polyurethane acrylates were used to generate cross-linked polyurethane films via UV initiated po-lymerization with and without cargo incorporation. Degradation experiment indicated that in PBS/H 2 O 2 /CoCl 2 the films degraded rapidly compared to PBS alone or with lipase. The polyurethane membrane loaded with the antibiotic tetracycline, demonstrated prolonged release over 200 h, suggesting that the polymers could be used as an implant coating for controlled drug release.
Journal of Pharmaceutical Sciences, 2008
Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres and nanoparticles remain the focus of intensive research effort directed to the controlled release and in vivo localization of drugs. In recent years engineering approaches have been devised to create novel micro-and nano-particles which provide greater control over the drug release profile and present opportunities for drug targeting at the tissue and cellular levels. This has been possible with better understanding and manipulation of the fabrication and degradation processes, particularly emulsionsolvent extraction, and conjugation of polyesters with ligands or other polymers before or after particle formation. As a result, particle surface and internal porosity have been designed to meet criteria-facilitating passive targeting (e.g., for pulmonary delivery), modification of the drug release profile (e.g., attenuation of the burst release) and active targeting via ligand binding to specific cell receptors. It is now possible to envisage adventurous applications for polyester microparticles beyond their inherent role as biodegradable, controlled drug delivery vehicles. These may include drug delivery vehicles for the treatment of cerebral disease and tumor targeting, and codelivery of drugs in a pulsatile and/or time-delayed fashion.
Salting-Out Waterborne Catiomeric Polyurethanes for Drugs Encapsulation and Delivery
Macromolecular Chemistry and Physics, 2015
Novel polyurethane (PU) catiomers with high urethane density are explored as templates for self-assembling into drug-carrying nanomicelles via a salting-out method. The micelles sizes, the salting-out effi ciency, and drug encapsulation effi ciency have been analyzed by dynamic light scattering and UV-vis. The ratio catiomeric/hydrophobic in the PU blocks structure infl uences the micelle hydrodynamic diameters varying from ≈50 to 200 nm. The encapsulating effi ciencies of different model drugs (MDs) have been analyzed. The infl uence of MD nature and PU catiomeric/hydrophobic blocks ratio on MD release kinetics has been evaluated, showing how PU, MD nature, and the pH infl uence on the MD release patterns. These results pave the way to the design of tuned copolymers for controlled release kinetics of specifi c drugs.
The Pharma Innovation Journal, 2019
Biodegradable polyurethane is considered as a potent biomaterial in various field of biomedical engineering. Polyurethane as a polymer shows their ability to get the product with wide variety of physical and mechanical properties. Biodegradable polyurethane membrane was composed by reacting PEG 400 and HDI in presence of DBTDL, catalyst. Morphological feature and functional group were analyzed by FESEM and FTIR. Degradation, cytotoxicity and in vitro antimicrobial activity were evaluated. In vitro drug release profile was analyzed using lysine hydrochloride drug. The material presented in this study shows the effective release of lysine hydrochloride which may consider as an efficient material for further study and clinical research.
PH Responsive Polyurethane for the Advancement of Biomedical and Drug Delivery
Polymers
Due to the specific physiological pH throughout the human body, pH-responsive polymers have been considered for aiding drug delivery systems. Depending on the surrounding pH conditions, the polymers can undergo swelling or contraction behaviors, and a degradation mechanism can release incorporated substances. Additionally, polyurethane, a highly versatile polymer, has been reported for its biocompatibility properties, in which it demonstrates good biological response and sustainability in biomedical applications. In this review, we focus on summarizing the applications of pH-responsive polyurethane in the biomedical and drug delivery fields in recent years. In recent studies, there have been great developments in pH-responsive polyurethanes used as controlled drug delivery systems for oral administration, intravaginal administration, and targeted drug delivery systems for chemotherapy treatment. Other applications such as surface biomaterials, sensors, and optical imaging probes are...
Biomacromolecules, 2015
Polyurethanes are a unique class of biomaterials that are widely used in medical devices. In spite of their easy synthesis and excellent biocompatibility, polyurethanes are less explored for controlled drug delivery due to their slow or lack of degradation. In this paper, we report the design and development of novel acid degradable poly(acetal urethane) (PAU) and corresponding triblock copolymer micelles for pH-triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX). PAU with Mn ranging from 4.3 to 12.3 kg/mol was conveniently prepared from polycondensation reaction of lysine diisocyanate (LDI) and a novel diacetal-containing diol, terephthalilidene-bis(trimethylolethane) (TPABTME) using dibutyltin dilaurate (DBTDL) as a catalyst in N,N-dimethylformamide (DMF). The thiol-ene click reaction of Allyl-PAU-Allyl with thiolated PEG (Mn = 5.0 kg/mol) afforded PEG-PAU-PEG triblock copolymers that readily formed micelles with average sizes of about 90-120 ...
Biodegradable micro and nanoparticles for controlled drug release
Abstract: Biodegradable polymeric micro and nanoparticles have shown to be promising forms for the delivery of a wide array of drug formulations, such as hydrophobic or hydrophilic active principles, proteins or other bio molecules. The aim of this study was to prepare micro and nanospheres starting from commercial polyesters, such as Poly-ε-Caprolactone (PCL) and Poly Lactic Acid (PLA) or proprietary polyester-urethanes (PU), for the controlled and targeted delivery of the anticancer drug Paclitaxel (PX) which has ...