The Application Of Poly (Lactic Acid) Nanofibers In Drug Encapsulation And Chronic Wound Treatments

Chronic wounds are of high incidence,difficult to heal,and can cause serious consequences if not properly treated.Bioactive dressings play an important role in the treatment of chronic wounds.The electrospun nanofibers of aliphatic polyester polymer have characteristics of non-toxicity,moisture retention,air permeability,antibacterial,and promoting skin regeneration,etc.They thus own advantages for applications in encapsulating drug to construct bioactive dressings and treating chronic wounds.At present,there are three problems when electrospun polyester nanofibers are used for drug encapsulation:(1)The encapsulation process involves harsh physical or chemical conditions,which destroy the biological activity of the drugs.(2)The drugs are not homogenously distributed in nanofibers,leading to poorly controlled release behaviors.(3)Only a single type of drug is encapsulated in nanofibers,the efficacy of which is limited.These problems lead to the limited therapeutic efficacy of electrospun polyester nanofibers on chronic wound treatments.In this study,we intended to rationally design the preparation methods for drug encapsulation of electrospun polyester nanofibers and realize that macromolecular protein drug or small molecular protease inhibitor drug can retain their biological activity and sustained release from nanofibers.The encapsulation methods for the above two types of drugs were then integrated to develop electrospun polyester nanofibers encapsulating two types of drug simultaneously.The therapeutic efficacy of polyester nanofibers on chronic wound treatments was further improved by the synergistic effects of the two types of drug.The work includes three parts:In the first part,we rationally designed the particle preloading method for fabricating electrospun poly(lactic acid)nanofibers encapsulating and controlled releasing bioactive protein drug.Firstly,we used positively charged chitosan nanoparticles as preliminary carriers to absorb negatively charged protein in mild condition.The preloading particles of small size were then dispersed in poly(lactic acid)solution in 1,1,1,3,3,3,-hexafluoro-2-propanol(HFIP)and subjected to electrospinning.The zeta potential of preloading particles was between + 5 m V and +32 m V.The size of preloading particles was between 90 nm and 712 nm.The zeta potential and size of preloading particles could be tuned by adjusting the amount of the input protein.The encapsulation efficiency of protein was more than 90%,and theloading content of protein was between 8% and 20%.The obtained protein encapsulated nanofibers were of smooth surface,uniform size,and with preloading particles homogeneously embedded inside.Protein retained their bioactivity and could release from nanofibers in a sustained manner for more than 4 weeks without initial burst.The nanofibers showed good cytocompatibility,could support cell adhesion and spreading and induce cell proliferation efficiently.The epidermal growth factor encapsulated nanofibers prepared with this method were more effective in promoting the healing of the wounds on the back of diabetic rats than blank nanofibers.In the second part,we prepared doxycycline encapsulated poly(lactic acid)nanofibers by the simple blending electrospinning method.The encapsulation of doxycycline by nanofibers could sustain the release of doxycycline and improve its therapeutic efficacy on chronic wound treatments.Doxycycline and poly(lactic acid)were dissolved into their common solvent HFIP together and subjected to electrospinning.Doxycycline was homogeneously distributed in nanofibers.The wettability of the nanofibers and release rate of doxycycline(sustained release 3 days to 2 weeks)could be controlled by adjusting the loading content of doxycycline.The doxycycline encapsulated nanofibers showed good cytocompatibility,could support cell adhesion,and promoted the healing of wounds on the back of diabetic rats to a higher extent than directly applied doxycycline.In the third part,we integrated the previously developed methods for encapsulating protein and protease inhibitors in nanofibers,and developed poly(lactic acid)nanofibers encapsulating the two types of drug simultaneously.The therapeutic efficacy of polyester nanofibers on chronic wound treatments was further improved by the synergistic effects of the two types of drug.The preloading nanoparticles were dispersed in the blend solution of doxycycline and poly(lactic acid)in HFIP and subjected to electrospinning.The preloading particles and doxycycline were homogeneously distributed in nanofibers.Protein could release from nanofibers in a sustained manner for more than 4 weeks without initial burst.Doxycycline could release from nanofibers in a sustained manner for more than 2 weeks.The nanofibers showed good cytocompatibility,and could support cell adhesion.The epidermal growth factor and doxycycline encapsulated nanofibers prepared by this method were more effective in promoting the healing of the wounds on the back of diabetic rats than nanofibers encapsulating only a single type of drug.