1-monooleoyl-rac-glycerol and osteum

Nanostructured hydrogels composed by biocompatible molecules are formulated and characterized. They are based on a polymer network formed by hydrophobically modified chitosans (HMCHIT or CnCHIT) in which vesicles of monoolein (MO) and oleic acid or sodium oleate (NaO), depending on pH, are embedded. The best conditions for gel formation, in terms of pH, length of the hydrophobic moieties of chitosan, and weight proportion among the three components were estimated by visual inspection of a large number of samples. Among all possible combinations, the system C12CHIT-MO-NaO in the weight proportion (1:1:1) is optimal for the formation of a well-structured gel-like system, which is also confirmed by rheological experiments. Electron paramagnetic resonance (EPR) measurements unambiguously show the presence of lipid bilayers in this mixture, indicating that MO-NaO vesicles are stabilized by C12CHIT even at acid pH. A wide small angle neutron scattering investigation performed on several ternary systems of general formula CnCHIT-MO-NaO shows that the length of the hydrophobic tail Cn is a crucial parameter in stabilizing the polymer network in which lipid vesicles are embedded. Structural parameters for the vesicles are determined by using a multilamellar model that admits the possibility of displacement of the center of each shell. The number of shells tends to be reduced by increasing the polymer content. The thickness and the distance between consecutive lamellae are not influenced by either the polymer or MO-NaO concentration. The hydrogel presented in this work, being fully biocompatible and nanostructured, is well-suited for possible application in drug delivery.

Topics: Chitosan; Drug Delivery Systems; Glycerides; Hydrogels; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Nanostructures; Oleic Acid; Rheology

Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release.

Topics: Analgesics; Clonidine; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Excipients; Gels; Glycerides; Hyaluronic Acid; Hydrophobic and Hydrophilic Interactions; Injections, Intra-Articular; Oleic Acid; Osteoarthritis; Soybean Oil; Time Factors; Viscosupplements

The present work aimed at evaluating the toxicity and genotoxicity of two organic (vesicles composed of sodium dodecyl sulphate/didodecyl dimethylammonium bromide-SDS/DDAB and of monoolein and sodium oelate-Mo/NaO) and four inorganic (titanium oxide-TiO₂, silicon titanium-TiSiO₄, Lumidot-CdSe/ZnS, and gold nanorods) nanoparticles (NP), suspended in two aqueous media (Milli Q water and American Society for Testing and Materials (ASTM) hardwater), to the bacteria Vibrio fischeri (Microtox test) and Salmonella typhimurium-his⁻ (Ames test with strains TA98 and TA100). Aiming a better understanding of these biological responses physical and chemical characterization of the studied NP suspensions was carried out. Results denoted a high aggregation state of the NP in the aqueous suspensions, with the exception of SDS/DDAB and Mo/NaO vesicles, and of nanogold suspended in Milli Q water. This higher aggregation was consistent with the low values of zeta potential, revealing the instability of the suspensions. Regarding toxicity data, except for nano TiO₂, the tested NP significantly inhibited bioluminescence of V. fischeri. Genotoxic effects were only induced by SDS/DDAB and TiO₂ for the strain TA98. A wide range of toxicity responses was observed for the six tested NP, differing by more than 5 orders of magnitude, and suggesting different modes of action of the tested NP.

Topics: Aliivibrio fischeri; Diffusion; Electrochemistry; Glycerides; Inorganic Chemicals; Luminescence; Luminescent Measurements; Metal Nanoparticles; Mutagenicity Tests; Mutagens; Oleic Acid; Organic Chemicals; Quaternary Ammonium Compounds; Salmonella typhimurium; Sodium Dodecyl Sulfate; Surface-Active Agents

The macroscopic appearance and microstructure in the dilute corner of the ternary monoolein (MO)-sodium oleate (NaO)-water (2H2O) system have been investigated by visual inspection and by using direct structural imaging with light microscopy and cryogenic transmission electron microscopy. The microstructural transformations that take place between the micellar phase (binary NaO2H2O axis) and the dispersed cubic phase (binary MO2H2O axis) upon increasing the ratio of MO to NaO are micelles, ruptured multilamellar vesicles together with flexible threads, various vesicle structures, vesicles in equilibrium with densely packed layers that either represent bilayers or domains of H(II) tubes visible from the side, and finally a pattern that may be either a cubic phase or domains of H(II) tubes visible in a cross section. Spontaneously formed uni- and multilamellar vesicles that show long-term stability are found to be the dominant structure for mixed dispersions over almost the entire concentration range. The addition of NaOH to the non-bilayer-forming system, the ternary MOOA (oleic acid)-2H2O system, leads to the formation of vesicles. Vesicles were also observed in other ternary MO-aqueous-based systems with potassium oleate, cetyltrimethylammonium bromide, sodium taurodeoxycholate, or dipalmitoylphosphatidylcholine instead of NaO.

Topics: Cetrimonium; Cetrimonium Compounds; Cryoelectron Microscopy; Glycerides; Liposomes; Micelles; Microscopy, Polarization; Oleic Acid; Phase Transition; Sodium Hydroxide; Surface-Active Agents; Taurodeoxycholic Acid; Water