The invention discloses 
minocycline hydrochloride nano sustained-release gel as well as a preparation method and application thereof, and belongs to the technical field of medicines. The problem of low encapsulation efficiency of small-molecule hydrophilic medicines is solved by introducing a form of a novel complex formed by chelating 
minocycline hydrochloride, 
metal ions and a compound with a plurality of 
sulfate, 
sulfonate or 
phosphate functional groups. Prepared 
minocycline hydrochloride multiple 
emulsion nanoparticles are smooth, round, high in encapsulation efficiency and strong in 
drug loading capacity. A prepared 
minocycline hydrochloride multiple 
emulsion nanoparticle is dispersed in a temperature-sensitive 
gel matrix to construct a double-layer 
delivery system which has certain 
biological adhesion, is good in periodontal retention and is convenient for administration. According to the 
minocycline hydrochloride nano sustained-release gel as well as the preparation method and application thereof, while the positioning 
advantage of the gel is exerted, burst release of a 
medicine can be remarkably reduced, the 
medicine administration period can be prolonged, possibility is created for further periodontal pocket local 
medicine administration treatment of 
periodontitis, the nanoparticles can penetrate through alveolar bone trabecula and bottom 
connective tissue, distribution of the medicine at a focus position is enhanced, and the 
antibacterial effect of the medicine is remarkably improved.