Low molecular weight heparin gels, based on nanoparticles, for topical delivery

• Published in: International journal of pharmaceutics Vol. 426; no. 1-2; pp. 256 - 262
• Main Authors: Loira-Pastoriza, C., Sapin-Minet, A., Diab, R., Grossiord, J.L., Maincent, P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2012; Elsevier
• Subjects: Acrylic Resins - chemistry; Administration, Cutaneous; Animals; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; drugs; Elastic Modulus; electrostatic interactions; enoxaparin; Enoxaparin - administration & dosage; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - blood; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - pharmacokinetics; Gel; Gels; Heparin, Low-Molecular-Weight - administration & dosage; Heparin, Low-Molecular-Weight - blood; Heparin, Low-Molecular-Weight - chemistry; Heparin, Low-Molecular-Weight - pharmacokinetics; Life Sciences; Low molecular weight heparin; Male; manufacturing; mixing; modulus of elasticity; molecular weight; Nadroparin - administration & dosage; Nanoparticles; Nanotechnology; Permeability; polymers; Rabbits; Rats; Rats, Wistar; Rheology; Skin - metabolism; Skin Absorption; Solubility; Technology, Pharmaceutical - methods; topical application; Topical delivery; Viscosity; Nanoparticles; Low molecular weight heparin; Topical delivery; Gel
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.01.044

A commercial suspension of nanoparticles (Eudragit® RS 30D) was used to manufacture a gel for topical application. Gels were prepared by mixing a polycationic polymer (Eudragit® RS 30D) and a low molecular weight heparin (LMWH), an antithrombotic agent. Gels formed spontaneously at a ratio of 1:1 as a result of electrostatic interactions between the polyanionic drug and the polycationic polymer. Different types of heparin were used: Bemiparin, Enoxaparin (Lovenox®), Nadroparin (Fraxiparin®) and Tinzaparin (Innohep®). Several LMWH concentrations were tested. Rheological measurements were performed to investigate the gel behavior. Gel formation was confirmed by dynamic rheological measurements as the elastic modulus (G′) was higher than the viscous one (G″). The amount of heparin incorporated into the gel matrix was determined. A maximum of incorporation (100%) was reached using a heparin solution of 600IU/mL. The release kinetics of LMWH from the gel were also studied. Regardless of the LMWH used in the formulation, a biphasic release profile was observed. Accordingly, a burst effect was observed. Afterwards, the release rate became steady. The penetration of the LMWH through the dermal barrier was also investigated.