The tetracyclines are broad-spectrum antimicrobial agents which inhibit protein synthesis by binding to the 30S ribosomal subunit. They exhibit activity against many Gram-positive and Gram-negative bacteria, Mycoplasma, Chlamydia and Rickettsiae, as well as spirochetes and some parasites. 1,2) Traditionally tetracyclines have been used for the treatment of a variety of infections including atypical pneumonia, diarrheal diseases, and periodontal diseases.2) Recent years, the additional application besides antimicrobial effects of tetracyclines has been discovered and developed. For example, tetracyclines contribute to the impaired collagen biosynthesis and inhibition of matrix metalloproteases (MMPs) indicating their potential use in the treatment of diabetes and osteoarthritis.3,4) However, drug-resistance, a common problem confronted by almost all antibiotics, and side effects accompanied with long-term administration of tetracyclines limit their use in many infectious diseases and other area. 1,2) Sustained-release drug delivery systems are regarded as promising formulations to improve therapeutic efficacy and safety of drugs by delivering them at a rate dictated by the need of the physiological environment over a period of treatment to the site of action. The most often used sustainedrelease drug delivery systems include hydrogels, microspheres, liposomes, micelles, nanoparticles, and nanocrystals. Among the various sustained-release drug delivery systems, solid lipid nanoparticles (SLN) are attracting major attention due to their unique advantages, such as good tolerability, larger scale production, possibility of controlled released targeting, less acute and chronic toxicity, and avoidance of toxic organic solvents. 5,6) So far, a few tetracyclines sustained release formulations such as, microspheres, 7) hydrogel, 8) liposome 9) and fiber 10) have been developed. Although SLN sustained release drug delivery system has many advantages compared to these systems, no tetracycline-loaded SLN has been reported to our knowledge. On the other hand, different routes of administration may result in varying effects on the biodistribution pattern of drug carriers. 5,11) The pharmacokinetics and biodistribution characteristics of drug encapsulated SLN have been well characterized and compared following intravenous (i.v.) injection, [12][13][14] and oral (per os (p.o.)) administration. However, few attempts have been done on the biodistribution of drug encapsulated SLN after subcutaneous (s.c.) administration. 15,16) The aim of this work was to prepare tetracycline-loaded solid lipid nanoparticles (Tet-SLN), and to investigate the biodistribution of Tet-SLN after subcutaneous administration in mice.
Results and DiscussionConstruction of Ternary Phase Diagrams The prerequisite to obtain a sufficient loading capacity is a sufficiently high solubility of the drug in the lipid melt. Albeit tetracycline is poorly soluble in lipids used in the study, it is soluble in ethanol. Besides, both glyceryl monostearate (GM) and steari...
