sorbitan-monooleate and oleylamine

Mucoadhesive olaminosomes are novel nanocarriers designed to control agomelatine release and enhance its bioavailability. Olaminosomes were prepared using oleic acid, oleylamine and sorbitan monooleate adopting thin film hydration technique. Chitosan HCl was added to impart the mucoadhesive properties to the olaminosomes. Mucoadhesive olaminosomes were characterized for their particle size, in-vitro drug release and irritation potentiality in rabbit eyes. The reduction in intraocular pressure (IOP) through 8 h in male New Zealand Albino rabbits was measured after administration of the selected formulations. Histopathological changes in rabbits' eye were also evaluated. Results revealed that increasing the amount of the added oleylamine decreased the particle size of the resulted vesicles and increased the drug release rate. Olaminosomes showed enhanced drug absorption, hence more reduction in IOP was observed. Moreover, using chitosan HCl might increase the residence time of the formulation in the eye and hence improved the absorption of the drug. No histopathological changes in rabbits' eye were detected after the application of mucoadhesive olaminosomes concluding their safety on the ocular tissues. In conclusion, mucoadhesive olaminosomes succeeded in enhancing agomelatine bioavailability in rabbits' eyes confirming the development of a novel ocular nanocarrier for insoluble drugs.

Topics: Acetamides; Adhesives; Administration, Ophthalmic; Amines; Animals; Biological Availability; Chemistry, Pharmaceutical; Chitosan; Drug Carriers; Drug Delivery Systems; Drug Liberation; Hexoses; Intraocular Pressure; Male; Ocular Hypertension; Oleic Acid; Particle Size; Rabbits; Solubility

The existing strategies in the design of non-viral vectors for gene therapy are primarily conceived for cationic systems. However, the safety concerns associated with the use of positively charged systems for nucleic acid delivery and several reports regarding the efficacy of negatively charged systems highlights the need for improved gene-delivery vectors. With these premises in mind, we investigated the development of new negatively charged nanoparticles based on Sorbitan esters (Span(®)) – extremely cheap excipients broadly used in the pharmaceutical industry – on the basis of a simple, one-step and easily scalable procedure. For their specific use in gene therapy, we have incorporated oleylamine (OA) or poly-L-arginine (PA) into these nanosystems. Thus, we used Sorbitan monooleate (Span(®) 80) to design Span(®) 80-oleylamine and Span(®) 80-poly-L-arginine nanosystems (SP-OA and SP-PA, respectively). These systems can associate with the model plasmid pEGFP-C3 and show mean particle sizes of 304 nm and 247 nm and surface charges of -13 mV and -17 mV, respectively. The nanoparticles developed were evaluated in terms of in vitro cell viability and transfection ability. Both systems exhibited an appropriate cell-toxicity profile and are able to transfect the plasmid effectively. Specifically, the nanosystems including OA among their components provided higher transfection levels than the SP-PA nanoparticles. In conclusion, anionic nanoparticles based on Span(®) 80 can be considered low-cost, simple and efficient non-viral anionic gene-transfection systems.

Topics: Amines; Anions; Cell Survival; Excipients; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Green Fluorescent Proteins; HEK293 Cells; Hexoses; Humans; Nanoparticles; Particle Size; Peptides; Plasmids; Transfection