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. 2022 Jul 25;23(15):8181. doi: 10.3390/ijms23158181

Table 1.

Polyurethane drug delivery systems.

Drug/Drugs Type of PUs or Composites Type of DDSs Main Conclusions Ref.
DOX PEG-1500/bis-MPA/IPDI nano- and microparticles/injectable carriers
  • -

    Thermoresponsive PUs manifested an LCST that could be easily tuned from 30 °C to 70 °C by increasing the PEG content.

  • -

    Temperature-responsive PU nanoparticles were characterized by a highly controlled DOX release.

 [35]
DOX HDI/PCL/PEG microcapsules
  • -

    pH-sensitive PU-DDSs were easily internalized by BGC 823 and Hela cells.

  • -

    PU-DDSs were characterized by a highly controlled drug release.

 [36]
DOX PU-SS-COOH: PEG-1000/PCL-2000/HDI/CYS/DMPA; PU-SS-COOH-NH2: PEG-1000/PCL-2000/HDI/CYS/DMPA/1,6-diaminohexane micelles
  • -

    The DOX release rate from the redox-sensitive PU micelles was controlled by the addition of GSH.

  • -

    DOX-loaded PU micelles displayed high cytotoxicity against tumor cells.

 [37]
DOX LDI/PEG-PU(SS)-PEG/ micelles
  • -

    DOX-loaded PU micelles had good stability under the extracellular physiological environment, but the drug was released quickly under the intracellular reducing conditions.

  • -

    DOX-loaded PU micelles had a high in vitro anti-tumor activity in C6 cells;

 [38]
DOX PHBHx/PEG-2000/PPG-2050/HDI thermogel
  • -

    DOX was released from thermogel with zero-order kinetics during 10 days.

  • -

    DOX-loaded thermogels showed an enhanced anti-melanoma effect on melanoma solid tumors and no apparent harm to other tissues, including liver, heart, spleen, kidney, and lung tissues.

 [39]
DOX LDI/mPEG-OH-5000/PCL; PCL obtained form ε-CL to 2,20-dithiodiethanol micelles
  • -

    DDSs for osteosarcoma therapy were obtained.

  • -

    In vitro, DOX-loaded PU micelles displayed significant anti-tumor activity, which was comparable with that of free DOX, against Saos–2 cells.

 [40]
DOX PTMC-SS-PTMC/CDI/PEOtz-OH micelles
  • -

    The pH and redox dual stimuli-responsive PU micelles were characterized by controlled DOX release to C6 cells.

 [41]
DOX HDI/2,2-bis(hydroxymethyl) propionic acid/PEG; amphiphilic PUs with carboxyl pendent groups nanoparticles
  • -

    pH-sensitive PU nanoparticles (NP) had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF-7) cells than that of pure DOX.

 [42]
DOX IPDI/methoxyl-poly(ethylene glycol) (mPEG)/carboxylic acid/piperazine micelles
  • -

    The drug release of DOX-loaded PS–PU micelles showed an obvious step-up with the reducion of the pH.

  • -

    The charge-reversal property improved the cellular uptake behavior and intracellular drug release in both HeLa cells and MCF-7 cells.

 [43]
DOX mPEG-5000/HDI/trimethylolpropane/bis(2-hydroxyethyl) disulfide core-shell nanogels
  • -

    GSH-responsive PU-based core-shell nanogels with hydrophilic mPEG shell were prepared.

  • -

    GSH triggered the nanogel swelling and accelerated the loaded drug release in PBS (pH = 7.4).

 [44]
DOX poly(2-oxazoline)s/PLA-SS-PLA/LDI micelles
  • -

    The release of the drug was stimulated in an acidic and reductive environment.

  • -

    The DOX-loaded PU micelles had high activity against C6 (rat glioma cells) cells.

 [45]
DOX PEG-2000/HDI and PCL-2000/PEG-2000/HDI nanomicelles
  • -

    PU micelles had higher cytotoxicity compared with pure DOX.

  • -

    The obtained micelles had better tumor inhibition ability and safety than that of pure DOX.

  • -

    DOX micelles had almost no burst release of the drug in a pH 7.4 environment.

 [46]
DOX mPEG-1000 (or PEG-2000)/poly(1,3-propylene succinate) diols (PPS)/IPDI micelles
  • -

    The enzymatic degradation of the micelles for 8 weeks under the physiological environment revealed that the degradation mainly occurred at the ester group of PPS blocks.

  • -

    A cytotoxicity test proved that the PU micelles were non-toxic, while the DOX-loaded micelles showed concentration-dependent cytotoxicity to HeLa cells.

 [47]
DOX PLA-SS-PLA/LDI/PEG micelles
  • -

    DOX was released quickly under intracellular reducing conditions.

  • -

    CCK-8 assays showed that DOX-loaded PU micelles had high in vitro anti-tumor activity in C6 cells.

 [48]
DOX WPU/CS membranes
  • -

    Waterborne polyurethane (WPU) and chitosan (CS) composite membranes exhibited fine biodegradability, favorable cytocompatibility, excellent blood compatibility, and a well-sustained release effect manifested in slow release, stability, and no sudden releases.

  • -

    DOX can be released efficiently from the drug-loading matrix and taken up by tumor cells.

 [49]
DOX mPEG-1900/PCL/LDI; PUs with benzoic-imine linkage micelles
  • -

    The cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage could act as an on–off switch, which is capable of activating clicked targeting ligands under an extracellular acidic condition, followed by triggering a core degradation and payload release within tumor cells.

 [50]
DOX polycondensation products of ortho ester-based diols and HDI (or HMDI) microparticles
  • -

    pH-sensitive POEUs NP were stable at physiological condition (7.4), were characterized by an accelerated degradation at a mildly acidic pH (5.0), an effective intracellular delivery of DOX, and high anti-tumor activity against 2D monolayer cells in vitro, and significantly enhanced the penetration of DOX into 3D multi-cellular tumor spheroids.

 [51]
DOX polycondensation product of terephthalilidene-bis(trimethylolethane) and LDI (and next termination process with allyl alcohol) nanomicelles
  • -

    In vitro DOX was released from obtained nanomicelles in a controlled and pH-dependent manner.

  • -

    DOX-loaded PU micelles had high in vitro anti-tumor activity in both RAW 264.7 and drug-resistant MCF-7/ADR cells.

 [52]
DOX trans-4,5-dihydroxy-1,2-dithiane
(O-DTT)/HDI/mPEG		 nanomicelles
  • -

    DOX-loaded PU micelles exhibited high anti-tumor efficacy in vivo with reduced toxicity.

 [53]
DOX PEG-2000/bis-1,4-(hydroxyethyl) piperazine (HEP)/O-DTT/HDI nanomicelles
  • -

    PU micelles tended to decompose under a weakly acidic environment or in the presence of an intracellular reducing agent (GSH).

 [54]
DOX LDI/PDO/PEG/PCL/folic acid (FA) nano- and micelles
  • -

    FA-conjugated PU micelles displayed a sustained DOX release, preferential internalization by human epidermoid carcinoma cell line (KB cells), and pronounced cytotoxicity compared with PU micelles without FA.

 [55]
DOX PCL/poly (tetramethylene ether) glycol/HDI cellulose acetate/PU/carbon nanotubes/composite nanofibers
  • -

    The synergic effects of composites and DOX-loaded nanofibers on the death of LNCaP prostate cancer cells were observed.

 [56]
DOX LDI/hydrazine/dihydroxy carboxybetaine conjugates/nano- and micromicelles
  • -

    pH-responsive PU-DDSs showed high stability in a physiological environment and continuously released DOX under acidic conditions. Carrier was virtually non-cytotoxic, while the prodrug micelles were more efficient in killing tumor cells.

 [57]
DOX Dipentaerythritol/HDI/mPEG-2000/glycerol conjugates/nanomicelles/dendritic PU
  • -

    PU-DDSs showed excellent pH/ultrasound dual-triggered drug release and tumor growth inhibition performance.

 [58]
DOX and PACL PLA-SS-PLA/IPDI/PEG micelles
  • -

    PACL release from DDSs was significantly accelerated by redox stimuli.

  • -

    PU micelles showed high cytotoxicity against HepG2 tumor cells.

 [59]
ECG MEG/BDO/PEG-200/HDI/IPDI microparticles
  • -

    The in vitro cytotoxic effect of obtained PU loaded with ECG on human pharyngeal carcinoma cells (Detroit 562) and squamous cell carcinoma (SCC-4) was observed.

 [60]
5-FU HDI/PEG-650 or -1250 or -1500 or -2000/1,2−DAE or 1,6-DAH or 1,4-DAB or 1,8-DAO/L-LYS WPU
  • -

    WPU were characterized with highly controlled drug-released kinetics.

  • -

    The 5-FU release rate was easily controlled in relation to the chain length of the chain extender and Mw of PEG.

 [61]
5-FU and PACL (PCL/HDI)/PNIPAAm grafted-chitosan core-shell nanofibers core-shell nanofibers
  • -

    PACL and 5-FU were released from nanofibers under a acidic and physiological pH with high control (and no burst release of drugs).

  • -

    The minimum increase in tumor volume was obtained using PACL and 5-FU loaded-nanofibers coated by magnetic gold nanoparticles.

 [62]
METX PCL-b-PEG-b-PCL/BDI/
L-glutathione oxidized		 films
  • -

    In some cases, the drug was released with sustained highly controlled kinetics over a period of 96–144 h (with near zero-order kinetics).

 [63]
PACL L-LYS-GQA/L-LYS-ABA-ABA tripeptide/HPCL/HPEG/LDI/PDO nanomicelles
  • -

    Nanocarriers improved cellular internalization and triggered intracellular PACL release in response to acidity within tumor cells.

 [64]
PACL PEG-1000/PCL-2000/LDI/BDO/CYS or PEG-1000/PCL-2000/LDI/MDEA/BDO or PEG-1000/PCL-2000/LDI/CYS/MDEA micelles
  • -

    PACL was released from PU micelles within 48 h in response to acidic and reductive stimuli;.

  • -

    Intracellular release of anti-cancer drug and internalization into H460 cancer cells was evidenced.

 [65]
PACL PCL-co-PEG/HMDI nanoparticles
  • -

    A biodistribution study of healthy mice evidenced no relevant differences between the commercial drug (Taxol) and obtained NP forms of PACL.

 [66]
PACL and TMZ PU purchased from Lubrizol Co magnetic particles incorporated into nanofibers
  • -

    Magnetic MIL-53 nanometal organic framework particles incorporated into poly(acrylic acid) grafted-CS/PU core-shell nanofibers were obtained.

  • -

    Nanofibers induced maximal apoptosis of U-87 MG glioblastoma cells.

 [67]
TMZ PCL/HDI/BDO
  • -

    NP incorporated into nanofibers;

  • -

    gold-coated NP-loaded PU nanofibers;
  • -

    NP (CS/TMZ) incorporated into nanofibers (PU/TMZ) and gold-coated (CS/TMZ) NP-loaded PU nanofibers were obtained.

  • -

    The obtained nanofibers inhibited the growth of U-87 MG human glioblastoma cells.

  • -

    Sustained TMZ release from DDSs for 30 days with the zero-order kinetic model was achieved.

 [68]
DOX polycondensation products of multi-functional L-lysine monomers/1,12-dodecanediol nanomicelles
  • -

    The amphiphilic aliphatic PU (APU) nanocarriers showed thermoresponsiveness above the lower LCST at 41–43 °C corresponding to cancer tissue temperature.

  • -

    The DOX-loaded APU nanoparticles accomplished more than 90% cell death in breast cancer (MCF 7) cells.

 [69]
GEF TDI/unknown polyol/unknown cross-linker (Vysera Biomedical Ltd.); GEF-loaded PLGA-based microspheres PU foams either as micronized
drug or as GEF-PLGA microspheres
  • -

    The coating of drug-eluting stents for the palliative treatment of bronchotracheal cancer was obtained.

  • -

    The drug was released with sustained highly controlled kinetics of GEF over a period of nine months (with zero-order kinetics).

 [70]
PACL MDI/PCL-4000/BDO membrane
  • -

    Temperature-responsive PU membranes exhibited a switching temperature at 44 °C.

  • -

    Below the switching temperature, shrunken free volume within the polymeric matrix prevented the incorporated PACL from diffusing out; upon heating above the switching temperature, the PU membranes rapidly switched on, allowing dramatically accelerated drug diffusion.

 [71]
CYCLOPHO TDI/PEG-600 (or -1500 or -3500)/DEG implant
  • -

    High control of the CYCLOPHO release from PU-DDSs

  • -

    Reduced toxic action of PU-DDSs compared with drug injections (in vivo tests—rats)

 [72]
DOX MDI/PPG-N3/PPEG-2000 or PPEG-4000 micelles
  • -

    At pH 6.0, DOX was rapidly released from pH-responsive PU micelles.

  • -

    Released DOX exerted potent anti-proliferative and cytotoxic effects in vitro.

  • -

    Micelles safely and efficiently delivered DOX into the cell nuclei.

 [73]
5-FU PCL (or PLA, CL/LA copolymers)/HDI conjugates
  • -

    In some cases, a highly controlled release of 5-FU over a period of 35 days was observed (with near zero-order kinetics).

 [74]