Construction Of Drug Loaded Globin Nanoparticles And The Targeting Delivery Study

With the development of nano science,nanotechnology has pervaded in multiple areas of medicine.In recent decades,with the rising incidence and mortality of cancer,people have paid great attention to the nanotechnology.Nowadays,several nanoparticle-based drug delivery systems have entered the market,which are used to diagnose diseases or to cure diseases.The success of these nanoparticle-based drug delivery systems is attributed to at least two aspects,one is that people has thoroughly and accurately understood the progress of the occurrence and development of some diseases,and the other one is that choosing the right drug carriers to delivery drugs.As a typical amphiphile macromolecule,protein not only has the ability of binding with hydrophobic drugs,but also has the ability of melting into the hydrophilic environment.Protein is biocompatible,biodegradable,low immunogenic and low toxic,so it is a good candidate for drug delivery.Addition to these advantages,there are diverse receptors coupling with different proteins in vivo.If use the protein as the drug carrier,it might achieve the goal of targeted delivering drug by one step,which can reduce the complexity of procedures in drug manufacture.For these reasons,protein becomes the favourite drug carrier used in drug delivery area.In this work,hemoglobin was processed under a low temperature to remove heme,the toxic prosthetic group,and expose its hydrophobic domain,and then the apohemoglobin(globin)was used as a drug carrier to produce drug loaded nanoparticles.Finally,we obtained stable nanoparticles with well controlled size.After that,researches were carried out to reveal the mechanism of nanoparticle formation and control release ability of the nanoparticles.We also set up suitable in vitro and in vivo model to evaluate the targeted delivery ability of the drug loaded nanoparticles.Specific work contents are as follows:(1)Heme was removed from hemoglobin by using acidic acetone under a low temperature to obtain globin,which had refolding ability with an empty hydrophobic domain.Adding paclitaxel ethanol solution to globin aqueous solution to prepare paclitaxel loaded globin nanoparticles(Gb-NPs-PTX).Studied the effect of pH and drug loading on nanoparticles sizes and stability.Characterized the nanoparticles and reveal the formation mechanism.The preparation condition was very tender,so that nanoparticles retained the biological activities of globin.Results from in vitro and in vivo assay indicated that Gb-NPs-PTX can be used to targeting deliver drug to CD163+ cells and organs.(2)Tanshinone ?A loaded globin nanoparticles(Gb-NPs-TA)were prepared via the same way as preparing Gb-NPs-PTX.Serial of assays were performed to characterize the Gb-NPs-TA.Results from pharmacokinetics study and tissue distribution study showed that Gb-NPs-TA significantly increased the solubility of tanshinone ?A and changed the features about tissue distribution,which can deliver more tanshinone ?A to liver faster.Then we set up a mouse model of hepatic fibrosis to evaluate the therapeutic effect of Gb-NPs-TA on hepatic fibrosis.Results indicated that Gb-NPs-TA could markedly improve liver function and delay the progression of fibrosis.The therapeutic effect of Gb-NPs-TA had an obvious advantage over the free tanshinone ?A,which may provide a guarantee for its clinical application in the future.