Preparation Of Composite TF-PLGA Slow-release Microcapsule And Its Drug-release Characteristics In Vitro

Objective:The loss of alveolar bone mass is associated with various oral diseases,which seriously affects patients' life quality.At present,using bone morphogenetic proteins(BMPs)to promote bone regeneration has achieved certain progress.However,their expensive price and unstable physicochemical properties,potential induced ectopic ossification and other shortcomings applying in bone tissue engineering were limitted in a certain extent.Based on the particularity of anatomical position of the oral and maxillofacial region,it's an objective requirement to find a safe,inexpensive and effective anti-inflammatory and antibacterial material.Chinese traditional medicine has a unique theoretical system for treating orthopedic diseases.As the pharmacological active ingredient of Rhizoma Drynariae,the total flavonoids of Rhizoma Drynariae(TFRD)can accelerate osteoblast division and propagation and inhibit osteoclast apoptosision.With the advanages on safety,stability and low price,it has been used in the study of bone tissue engineering.As the main pharmacological active ingredient of Chrysanthemum,the total flavonoids of Chrysanthemum(TFC)has antibacterial anti-inflammatory,scavenging oxygen free radicals and other biological activities.It can be used to treat various acute or chronic inflammation and infectious diseases.TFRD and TFC are both flavonoids which may demonstrate an estrogenic effect,promoting bone regeneration.By oral formation or injection of TF,the bioavailability is low,the target absorption is poor,and the treatment time is short,thus it is necessary to develop local sustained-release drugs.Based on current research and existing problems in bone defects,this study innovatively used TFRD and TFC as the Chinese herbal medicine preparation.polyactic-co-glycolic acid(PLGA)as the carrier,developing a new medicine to promote bone regeneration.The study aims to investigate the optimum prescription and slow-release characteristics in vitro through studying TF-PLGA microcapsules' physicochemical properties and drug-release situation.Methods:1.TF-PLGA microcapsules were prepared with TFRD,TFC and PLGA by emulsifying-solvent evaporation technique under certain conditions.2.With encapsulation efficiency(EE)as the index,the influence of formulation and manufacture was studied by single factor and orthogonal experiments,the optimal formulation was verified by orthogonal design;The drug-loading rate(DL)and encapsulation efficiency(EE)was evaluated by spectrophotometric method.3.The characteristics of TF-PLGA microencapsules,the average particle size and the distribution were observed under light microscopy(LM)and scanning electron microscopy(SEM).4.The constant temperature commotion method was selected to examine the drug release in vitro.Results:1.We successfully made the TF-PLG-MC by emulsifying-solvent evaporation technique under certain conditions.Processes of preparation were simple and feasible;2.The optimum prescription was A3B3C2D1,the concentration of PLGA=140g·L-1,oil phase volume=1.4 m L,emulsifying speed=900 r·min-1,emulsifing time=5min.After optimization,we got a high average encapsulation rate(ER)(95.28±0.29)%,average EE(83.89±2.30)% and good average DL(5.90±0.07)% for the first time;3.After optimization,the color of powder was light brown,TF-PLGA microcapsules presented as round and smooth ball under LM and SEM.The average particle size was(44.34±14.68)?m measured by Nano Measurer application,the distribution was relatively narrow;4.In vitro TF-PLGA microencapsules' cumulative sustained release time was about 50 d.The results showed that the initial release was about 40%.The burst release effects existed.Over time,the drug release rate remained stable.At 12 d,TF in vitro released over about 50%.After 30 d,TF release tended to be gentle.The cumulative drug release rate was over 90% after 50 d,with significant sustained-release effect.Conclusions:With roundless shape,uniform size,high EE and DL,the TF-PLGA microcapsules successfully prepared by optimized emulsifying-solvent evaporation technique posessed good sustained-release efficacy in vitro.The preparation process was simple and reproducible.This study provided a theoretical basis for optimizing local slow-release drugs for bone regeneration and a feasible measure for modifying Chinese traditional medicine compound dosage forms.