The self-assembly of biodegradable polyurethanes constitutes an important area of research for the development of polymeric materials in biomedicine. In particular, colloidal polyurethane assemblies can increase the solubility and stability of hydrophobic compounds, and improve the specificity and efficiency of drug action. Their nanoscale size and modular functionality make them promising for the injectable, targeted and controlled delivery of various therapeutic agents and imaging probes into required cells. Additionally, cationic polyurethanes are able to self-assemble with nucleic acids into nanoparticles to enter cells for efficient gene transfection. These emerging nanocarriers open the door for addressing the failure of traditional localized delivery systems, and present a compelling future opportunity to achieve personalized therapy as versatile candidates. This review article highlights the research progress in the self-assembly of biodegradable polyurethanes for controlled delivery applications, with particular attention being paid to some representative vehicles such as self-assembled polyurethane micelles, nanogels, and polyurethane/DNA complexes, which have emerged as the focus of interest in recent years.
To obtain a pH-sensitive multifunctional polyurethane micelle drug carrier, a novel pH-sensitive macrodiol containing acid-cleavable hydrazone linkers, poly(ε-caprolactone)−hydrazone−poly(ethylene glycol)−hydrazone−poly(ε-caprolactone) diol (PCL−Hyd−PEG−Hyd−PCL), was synthesized and characterized with proton nuclear magnetic resonance spectra (1H NMR). A series of pH-sensitive biodegradable polyurethanes (pHPUs) were designed and synthesized using pH-sensitive macrodiol, l-lysine ethyl ester diisocyanate (LDI) and l-lysine derivative tripeptide as chain extender, which can provide an active reaction site for the development of positive target polyurethane micelles for drug delivery. The bulk structures of the prepared polyurethanes were carefully characterized with 1H NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The polyurethanes could be cleaved in acidic media (pH ∼ 4−6) as well as degraded in PBS and enzymatic solution, as demonstrated by 1H NMR and weight loss, respectively. The cytotoxicity of their degradation products was evaluated using methylthiazoletetrazolium (MTT) assay in vitro, resulting in no apparent inhibition effect on the fibroblasts. These polyurethanes could self-assemble into micelles in aqueous solutions, as verified using dynamic light-scattering (DLS). Our present work provides a new method for the preparation of amphiphilic multiblock polyurethanes with pH-sensitivity and biodegradability. It could be a good candidate as biodegradable multifunctional carrier for active intracellular drug delivery.
Specific accumulation of therapeutics at tumor sites to improve in vivo biodistribution and therapeutic efficacy of anticancer drugs is a major challenge for cancer therapy. Herein, we demonstrate a new generation of intelligent nanosystem integrating multiple functionalities in a single carrier based on multifunctional multiblock polyurethane (MMPU). The smart nanocarriers equipped with stealth, active targeting, and internalizable properties can ferry paclitaxel selectively into tumor tissue, rapidly enter cancer cells, and controllably release their payload in response to an intracellular acidic environment, thus resulting in an improved biodistribution and excellent antitumor activity in vivo. Our work provides a facile and versatile approach for the design and fabrication of smart intracellular targeted nanovehicles for effective cancer treatment, and opens a new era in the development of biodegradable polyurethanes for next-generation nanodelivery systems.
A super-nanodevice engineered at molecular level integrates various desired properties in a smart and coordinated way, and can "switch on" or "turn off" certain functionalities as required. Importantly, it can break through complex physiological barriers, and then precisely ferry potent toxic triptolide into tumor cells in vivo, thus significantly maximizing the therapeutic efficacy and reducing the drug toxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.