ABSTRACT
A study of the parameters relating to the preparation of para-acyl-calix[9]arene-based solid lipid nanoparticles (SLNs) has been undertaken. Dynamic light scattering and electron microscopy have shown that the particle size varies between 85 and 215 nm depending on the acyl chain length. Parameters, including the organic solvent, amphiphile concentration and the presence of a co-surfactant affect the size of the SLNs obtained significantly. In contrast, stirring speed and solution viscosity have no effect. The ionic strength of the suspension has been shown to affect SLN stability in a salt-dependent manner. Ultrasonic and ultraviolet and 80°C treatment of the SLN suspensions have no effect on the SLN stability. The SLNs are unstable with respect to freezing–defreezing cycles, but can be reconstituted using mono- or disaccharides as cryoprotectants. Importantly, the temporal stability of these suspensions in water has been shown to be superior to 6 months. With regard to protein interactions, no SLN aggregation was observed in the presence of human serum albumin, with formation of a monolayer of albumin on the surface of the SLNs. Encapsulation was shown using acridine as a fluorescent probe.
Subject(s)
Calixarenes/chemistry , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Lipids/chemistry , Nanocapsules/chemistry , Nanoparticles/chemistry , Acylation , Cryoprotective Agents/chemistry , Cryoprotective Agents/pharmacology , Drug Stability , Lipids/administration & dosage , Microscopy, Electron , Nanocapsules/administration & dosage , Nanoparticles/administration & dosage , Organic Chemicals/chemistry , Particle Size , Scattering, Radiation , Solvents/chemistry , Surface-Active Agents/administration & dosage , Surface-Active Agents/chemistry , Suspensions/chemistry , Temperature , Time Factors , Viscosity , Water/chemistryABSTRACT
Twelve new di- and tetraderivatized alpha-cyclodextrin molecules having either alkylthio and perfluoroalkylpropanethio functions at the primary face have been synthesized by using the procedure of Sinay for di-O-debenzylation of perbenzylated alpha-cyclodextrins. A new strategy of protection/deprotection has been developed for introducing the lipophilic chains. The coupling reaction involves the reaction between the appropriate alpha-cyclodextin derivative, regioselectively modified at C-6 positions by a good leaving group (O-mesityl for disubstituted or iodine for tetrasubstituted derivatives), with the thioalkyl or the thioperfluoroakylpropane chains. These nucleophilic reagents are obtained from the in situ basic hydrolysis of the alkylisothiouronium bromides or perfluoalkylropropane and the isothiouronium iodides. These multistep reactions give the desired amphiphilic alpha-cyclodextrins in good overall yields of 33% to 58%.
