Preparation And Performance Of Keratin Nanoparticles As Drug Carriers

The design and preparation of multi-responsive sustained and controlled release formulations using nanotechnology have shown potential application in drug delivery.Nanocarrier based delivery system can effectively improve the functional defects of traditional dosage forms,and help to improve drug stability,dispersion,loading efficiency and release performance.Using nanocarrier system is an important way to improve drug efficacy and effective utilization,reduce residual pollution and reduce toxic and side effects.Based on the wide application of biocompatible nanoparticles as drug carriers in pharmaceutical preparation,a Keratin nanoparticle(KNP)based drug-carrying system was constructed in this study to explore its properties and applications as nano-drug carriers.Rhodamine B and curcumin were used as hydrophilic and hydrophobic model drugs,and gentamicin sulfate was used as bactericidal model drugs.The model drug loading system and bioassay system were established for efficacy evaluation.The main results are as follows:(1)Establishment and optimization of the keratin nanoparticles preparation method.Keratin nanoparticles were prepared by solvent method.The optimal preparation conditions were as follows: the ratio of absolute ethanol to keratin solution was 1:4,the concentration of glutaraldehyde was 1.25 %,the stirring speed was 500 rpm,and the cross-linking time was 2 h.The keratin nanoparticles were characterized by dynamic light scattering analysis(DLS)and Scanning electron microscopy(SEM).The particle size was about 300 nm.The keratin nanoparticles were evenly dispersed in the aqueous phase with abundant negative charges and good stability.(2)Model drug delivery systems were established with rhodamine B and curcumin as hydrophilic and hydrophobic model drugs.The drug loading capacity of KNP under different drug loading methods was evaluated.The results showed that rhodamine B could be loaded by(1)adsorption post the preparation or(2)addition during the preparation.The drug loading capacity and encapsulation efficiency of method(1)were 7.96 ± 0.31 % and 41.70 ± 1.09 %,respectively;The drug loading and encapsulation efficiency of mehod(2)were 9.64 ± 0.43 %and 43.28 ± 1.38 %,respectively.The addition method is more conducive to the loading of hydrophilic drugs.Curcumin was added into the organic phase during the preparation of the carrier to achieve drug loading,and the drug loading and encapsulation efficiency were 6.56 ±0.07 % and 41.37 ±1.82 %,respectively.The drug was successfully loaded onto KNP by FTIR,X-ray Diffraction(XRD)spectrogram analysis and Zeta potential characterization.It also suggests that the hydrophilic dye rhodamine B binds to KNP by hydrogen bond,while the hydrophobic dye curcumin binds to KNP by non-covalent interaction.In vitro release experiments proved that curcumin and rhodamine B loaded KPN showed better sustained release performance than bulk drugs,and also showed good p H and redox responsiveness controlled release properties.Using Saccharomyces cerevisiae as the model bioassay system,the uptake of Rhodamine B and curcumin loaded KNP by cells was detected.The results showed that KNP improved the cell uptake ability upon hydrophilic and hydrophobic drugs.(3)Using gentamicin sulfate as bactericidal mode drug,the KNP loading system was established.Addition method was adopted to load the drug and the optimal loading and encapsulation rate were 8.96 ± 0.08 % and 45.28 ± 0.43 %,respectively;The drug was proved to be successfully loaded on KNP by FT-IR analysis,XRD analysis,Zeta characterization and thermogravimetric analysis.In vitro release experiment showed that the gentamycin sulfate loaded KNP had good release performance compared with the bulk drug,and showed p H and redox responsiveness controlled release properties.Using gram-negative bacteria Escherichia coli as the model bioassay system,the inhibition of cell growth showed that KNP could prolong the duration of drug efficacy for 96 hours.In conclusion,this study constructed a keratin nanoparticle based drug delivery system and its properties and applications to be explored.The results provide a reference for the development of KNP as new drug carriers as well as the potential application of KNP in precision medicines.