Bleached shellac in situ forming micro-particle fabricated with different oils as antibacterial delivery system for periodontitis treatment

Abstract

In-situ forming micro-particle (ISM) is an emulsion system that could change into micro-particulate matrices by phase separation of matrix former. In this research work, bleach shellac (BS) was used as the matrix forming agent to develop the doxycycline hyclate (DH)-loaded ISM and the different oils were used as the external phase of non-aqueous in oil emulsion. ISMs were prepared by using BS dissolved in dimethyl sulfoxide (DMSO), N-methyl pyrrolidone (NMP), or 2-pyrrolidone (PYR) as the internal phase and the external phase containing glycerol monosterate (GMS) in various oils including camellia oil, canola oil, olive oil, safflower oil, and sesame oil. The physical properties of ISMs using PYR as the solvent of the internal phase were tested including viscosity, in vitro micro-particle formation, injectability, drug release, surface topography, and antibacterial activity against Porphyrommonas gingivalis. All DH-loaded ISMs were easy to be injected through a needle and formed into micro-particles after exposure to phosphate buffer. The external oil phase reduced the friction between barrel and plunger of syringe and thus promoting easier injectability. The particular drug-loaded ISM prepared from safflower oil was largest, while that prepared from sesame oil was smallest and that of the others had no significant difference (p < 0.05). After 60 sec, the particle size of drug-loaded formula had no presence of coalescence. DH released from BS ISM was sustainable longer than 50 days. Sponge topography of micro-particle after DH release test in SEM micrographs confirmed the solvent exchange initiated further phase separation of BS into a micro-particular sponge. They efficient inhibited against P. gingivalis with a sustainable drug release character from the retardation of drug diffusion. Thus, DH-loaded ISMs using PYR as the solvent of the internal phase could be fabricated with various oils and exhibited the potential use for periodontitis treatment.