| Baicalin in the treatment of brain diseases related pharmacological study was reported a lot,because the poor solubility and low bioavailability of baicalin,in under the action of the blood-brain barrier,the concentration of baicalin in brain tissue was difficult to achieve effective.The retention time in the nasal cavity of dry powder was longer than nose drops,nanoparticles had unique advantages in the brain targeted,but the size of the nanometer lead to nanoparticles couldn't inhaling through the nose to reach effective absorption area.This topic combined with the advantages of dry powder and the nanoparticles to prepare nanocomposite particles,the nanocomposite particles had been modified by the target body protein-lactoferrin on spray drying,and the related characterization,security,and in vivo pharmacokinetics and brain targeted research had been researched.The preparation of baicalin nanoparticles was used by compound emulsion and ionic crosslinking method respectively.The particle size,drug loadings,coating rate was used as a reference index,to determine the better method of noparticles preparation was ionic crosslinking method.The best process parameters were as follows:the quality ratio of the sodium phosphate polymer and chitosan was 1:5,pH was 5,the speed was 20000 r/min,distilled water washingtime was one,the solvent of baicalin was methanol,the volume ratio of methanol and acetic acid aqueous solution was 1:3.The drug loadings of the nanoparticles was 7.82%,the particle size was 170.5 nm.The nanocomposite particles was prepared by spray drying.The nanocomposite particles were characterized by by scanning electron microscopy,dry laser particle size analysis,X-ray diffraction,differential scanning calorimetry,powder flowability test,and were investigated by in vitro release in artificial nose liquid electrolyte and ex vivo rabbit nasal mucosa permeability experiment.Results of electron microscope scanning showed that nanocomposite particles which liked a kind of ball is composed of nanoparticles.The size of nanoparticles dispersed from nanocomposite particles was larger than the primary nanoparticles.Size distribution showed that average particle size of the nanocomposite particles was(6.8±0.4)?m,The average particle size of nanoparticles dispersed from nanocomposite particles was(510.4±20.4)nm.Results from X-ray diffraction and differential scanning calorimetry showed that baicalin dispersed in carrieris on the amorpHous state.The powder flowability test exhibited that the flowability of nanocompositeparticles was better than that of baicalin APIs,and ventilation performance is worse than chitosan.Results from in vitro release showed that the cumulative release rate of the nanocomposite particles samples was(78.85±2.71)%in 33 hours and the release curve accorded with Riger-Peppas model.In vitro rabbit nasal mucous membrane penetration test results showed that the value of cumulative release rate per unit area of the nanocomposite particles sample was 1.77 times that of the pure baicalin sample in 7 hours,,and osmolality was 198.07±7.07 ?g·cm-2The lactoferrin was added in nanoparticle suspension liquid to prepare lactoferrin modified nanocomposite particles by spray drying.The lactoferrin modification efficiency was as examining index to optimize the appropriate amount of lactoferrin to join.In order to further study the effect of lactoferrin on nanocomposite particles,the lactoferrin modified nanocomposite particles were characterized by scanning electron microscopy and ex vivo rabbit nasal mucosa permeability experiment,and safety evaluation by nasal mucosa toxicity study,hemolytic experiment and methanol residue detection.The lactoferrin modified nanocomposite particles into a kind of spherical,is composed of nanoparticle.In vitro rabbit nasal mucous membrane penetration test results showed that the value of cumulative release rate per unit area of the lactoferrin modified baicalin nanocomposite particles sample was 1.84 times that of the pure baicalin sample and 1.04 times that of the baicalin nanocomposite particles sample in 7 hours,and osmolality was 205.50 ?g·cm-2.Nasal mucosa toxicity test showed that it was basic nontoxic to nasal mucosa.Hemolysis rate was less than 5%which suggested that it was basic undamaged to cell membrane.Methanol residue content was less than 0.3%which was conformed to the requirement of pharmacopoeiaRat nasal cavity were given lactoferrin modified baicalin nanocomposite particles,nano composite particles,baicalin nanocomposite particles dispersed suspension liquid and baicalin API.respectively,with intravenous corresponding samples as a control.The baicalin content of plasma,cerebrospinal fluid,brain tissue from different parts and each viscera were determinated,and the results showed that the modification of lactoferrin and composite nanoparticles technology can enhance the bioavailability of baicalin and brain targeting,and the content of baicalin in the tissue of each viscera distribution was reduced significantly after nasal inhalation drug. |
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