Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid

• Published in: International journal of pharmaceutics Vol. 334; no. 1; pp. 179 - 189
• Main Authors: Attama, A.A., Müller-Goymann, C.C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.04.2007; Elsevier
• Subjects: Adipose Tissue - chemistry; Animals; Biological and medical sciences; Calorimetry; Crystallinity; Crystallization; Drug delivery; Drug Delivery Systems; Drug Stability; Drug Storage; General pharmacology; Goats; Heterolipid; Homolipid; In situ crystallization; Lipid nanocontainers; Lipids - chemistry; Medical sciences; Microscopy; Nanoparticles - chemistry; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines - chemistry; Polysorbates - chemistry; Surface modification; Surface Properties; Surface-Active Agents - chemistry; Temperature; Templation; Transition Temperature; X-Ray Diffraction; Surface modification; Homolipid; Lipid nanocontainers; Templation; Drug delivery; Heterolipid; Crystallinity; In situ crystallization; Drug; Delivery system; Pharmaceutical technology; Nanoparticle; In situ; Crystallization; Lipids; Ocular administration; Solid; Parenteral administration; Microparticle
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.10.032

There is increasing interest in the search for improved drug delivery systems with greater versatility. Consequently, many drug delivery systems have been studied. In this study, surface-modified lipid nanocontainers were formulated with a homolipid from Capra hircus (goat fat) templated with a heterolipid (Phospholipon 90G ®) which was also the surface modifier. The solid lipid nanocontainers (SLN) were formulated by hot high pressure homogenisation using increasing concentrations of polysorbate 80 as the mobile surfactant. Prior to SLN preparation, the templated homolipid was formulated by fusion to obtain a homogeneous lipid matrix, which was characterized using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and wide angle X-ray diffraction (WAXD) to obtain its thermal and crystal characteristics. Isothermal heat conduction microcalorimetry (IMC) and freeze-fracture transmission electron microscopy (FFTEM) studies were carried out on the templated homolipid and SLN containing 1.0% (w/w) of polysorbate 80 to study their in situ crystallization kinetics and morphology, respectively. The formulated SLN were also subjected to time-resolved DSC, WAXD and particle size analyses for one month. The thermal and crystal characteristics were compared with those of the bulk lipid matrix (templated homolipid). Result of the particle size analysis indicated that the particles size remained roughly within the lower nanometer range after one month. FFTEM micrograph of the lipid matrices revealed lamellar sheets for Phospholipon 90G ® and layered triglyceride structures for the homolipid and Phospholipon 90G ®-templated homolipid. FFTEM micrograph of SLN revealed anisometric structures. PLM of the templated homolipid did not show, but goat fat (homolipid) alone showed slight growth in crystals with time. WAXD and DSC studies revealed minor increase in crystallinity of the new lipid matrix after one month and DSC also detected templation of homolipid by the heterolipid noted by the disappearance of the lower melting peak of the homolipid. However, for the SLN, WAXD results showed low crystalline particles while DSC only showed a very little endothermic process after one month of storage at 20°C. The implication of this finding is that progression of the SLN to highly ordered particles over time would not occur. This will be favourable for any incorporated drug as drug expulsion, due to increase in crystallinity, will not occur. Result obtained from analysis of the isothermal crystallization exotherms indicated that the templated homolipid and SLN1 containing 1.0% polysorbate 80 possess similar nucleation mechanisms and growth dimensions different from the pure homolipid. The SLN containing 0.5 and 1.0% polysorbate 80 possessed good properties and could prove to be good delivery systems for drugs for parenteral or ocular administration. The result of this study also shows a method of improving natural lipids for use in particulate drug delivery systems.