Preparation And Evaluation Of Azithromycin-loaded Micelles

Azithromycin（AZI）is a macrolide antibiotic with broad-spectrum antibacterial properties.It was used to treat bacterial infections such as respiratory infections,skin infections and urinary system infections.AZI can inhibit the growth of bacteria by binding to the 50S subunit of bacterial ribosome and prevent the translation of amino acids.Nano drug delivery refers to the system which particle size range of 1000 nm formed by drugs and pharmaceutical materials,including nanoparticles,liposomes,drug loaded micel es,etc.The drug-loaded micel es are usual y formed by self-assembly of amphiphilic block copolymers in aqueous solution through hydrophobic interaction.Not only can it avoid direct contact of the drug with the gastrointestinal tract,which reduces the side effects of the drug,it can also prevent the drug from being swal owed by the reticuloendothelial system and prolong the action time in the body.In this paper,monomethoxy polyethylene glycol（Mw=2000Da）was used as the raw material to synthesize MPEG-（OH）₄ through condensation and hydrolysis ring-opening reaction.Then MPEG-（OH）₄ was performed N-acylation withα-linolenic（LNA）acid to form MPEG-（LNA）₄.Its structure was confirmed by nuclear magnetic resonance hydrogen spectroscopy（¹H-NMR）and infrared spectroscopy（FT-IR）.AZI-loaded micel es（AZI-M）were prepared by thin-film hydration,and the single factors affecting drug loading and encapsulation efficiency were investigated.On the basis,orthogonal design was carried out to select the best preparation process.X-ray diffraction（XRD）and FT-IR were used to study the presence of AZI in micel es.The in vitro release of micel es was studied.In terms of activity,Staphylococcus aureus was selected as the model bacteria,and AZI-M in vitro and in vivo activities were studied.The results showed that the optimal drug-loaded micelles were prepared with MPEG-（LNA）₄ dosage of 70 mg,AZI dosage of 10 mg,hydration temperature 60℃,aqueous phase dosage of 10 mL,and dichloromethane volume of 2 mL.In this condition,the encapsulation efficiency and loading capacity of AZI-M was 87.77±1.28%、10.97±0.16%,respectively.The particle size distribution of drug-loaded micel es was uniform,with a diameter of 105.80±1.16nm.Both XRD and FT-IR indicated that AZI was encapsulated in amphiphilic polymers and existed in AZI-M in an amorphous state.In vitro release studies had shown that drug-loaded micel es can release AZI more slowly and continuously than AZI.In terms of in vitro activity,the activity of AZI-M is comparable to that of the bulk drug.In terms of in vivo activity,the therapeutic effect of AZI-M is the same as that of commercially available preparations,all of perparations kill S.aureus in the abdominal cavity of mice.