Preparation And Characterization Of Functional Polyurethane Nanomicelle For Drug Delivery

Stimuli-responsive functional nanomicellar system for drug delivery was a kind of emerging and booming part in biomedical material system,nanomicelle has the special structure of a external hydrophilic shell and interior hydrophobic core,which could be used to embed hydrophobic drug.This would be very helpful in solving the deficiencies of traditional hydrophobic drugs,such as poor solubility and compatibility,low circulating capacity,significant side effects and easily rapid clearance by reticuloendothelial system(RES).The development and application of polyurethane materials has achieved more and more attention of researchers.That was all due to the wide range of raw materials,diversified designability of molecular structure,and mild preparation conditions.polyurethane nanomicelle was a kind of polymeric biomaterials with good biocompatibility,using polyurethane as matrix materials.Combining with stimulus responsive functional groups to the polyurethane molecule can obtain the stimuli-response polyurethane nanomicelle,which was expected to be used in the research of the application of nanomicelle of drug controlled release system.In this paper,three kinds of polyurethane micelle with p H single response or p H/ reduction response were synthesized.The first one was polyurethane PPU with 2,2-dihydroxymethylpropionic acid(DMPA)as anionic functional monomer and 2,6-lutidine(PDM)as cationic functional monomer;the second one was polyurethane BPU with 2-(diethanolamine)sodium ethyl sulfonate as zwitterionic monomer,which contained tertiary amine and sulfonic acid group simultaneously.On this basis,modification of polyester diol was carried out by cysteine dihydrochloride to achieve a new type of polyester diol containing disulfide bonds PNAL-SS,polyurethane BSPU was synthesised by PNAL-SS and BES-Na as functional monomers.After self-assembly,polyurethane nanomicelles PPU and BPU were p H-responsive,and polyurethane nanomicelles PPU was p H and redox dual responsive.Infrared spectrometry(FI-IR),nuclear magnetic resonance hydrogen spectrum(1H NMR)and elemental analysis were used to characterize the structure of polyurethane.Scanning electron microscope(SEM),transmission electron microscope(TEM)and dynamic light scattering(DLS)were used to analyse the morphology characteristics of polyurethane and particle size distribution.Folic acid was used as the hydrophobic model drug to explore drug loading and controlled releasing of polyurethane nanomicelle.As experiment results showed,the hydration particle size of PPU nanomicelles was around 120 nm,it is spherical and evenly distributed.The initial concentration of polyurethane had an effect on the formation of micelles.The loading content(LC)of PPU polyurethane was about 2.59% and the encapsulation efficiency(EE)was about 13.33%,the releasing rate of folic acid changed with the p H of the environmention.The above results showed that PPU polyurethane nanomicelle could be used as the drug carrier of p H-responsive function.The nuclear/shell double structure of BPU polyurethane micelles could be observed under transmission electron microscopy.With change of the content of functional monomer BES-Na and change of the feed ratio of hydrophilic/hydrophobic chain,the actual particle size changes accordingly.According to this change,the particle size of nanomicelle of polyurethane could be adjusted.In this experiment,the average size of BPU nanomicelle was about 100 nm,which was suitable for drug delivery.In vitro release test,the maximal loading content(LC)of BPU polyurethane micelle was about 7.68% for folic acid,which had large improvement compared with the PPU micelle,the cumulative drug release percent(Er)in 24 h can reach 79.17%(p H 6.8)and 89.83%(p H 5.0),the results showed that the BPU micelle was p H-responsive.Polyurethane BSPU was based on polyurethane BPU,disulfide bond with reduced responsiveness was introduced into the main chain structure of polyurethane by modification.With the introduction of this functional group,polyurethane micelle BSPU has become the double responsive polyurethane nanomicelle compared to the original one.In vitro simulation controlled releasing experiments,the result of research showed that the introduction of disulfide bond was helpful to enhance the stimulation responsiveness of polyurethane micelle and increase the releasing rate of folic acid.