Low molecular weight heparin gels, based on nanoparticles, for topical delivery.
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 600 IU/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.
EA 3452 Drug Targets, Formulation and Preclinical Drug Assessment, Faculty of Pharmacy, Nancy-University, 54001 Nancy Cedex, France.
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Loira-Pastoriza
EA 3452 Drug Targets, Formulation and Preclinical Drug Assessment, Faculty of Pharmacy, Nancy-University, 54001 Nancy Cedex, France.
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Sapin-Minet
EA 3452 Drug Targets, Formulation and Preclinical Drug Assessment, Faculty of Pharmacy, Nancy-University, 54001 Nancy Cedex, France.
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Diab
UMR CNRS 8612, Faculty of Pharmacy, Paris-Sud University, 5 Rue J.B. Clément 92296, Châtenay Malabry, France.
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Grossiord
EA 3452 Drug Targets, Formulation and Preclinical Drug Assessment, Faculty of Pharmacy, Nancy-University, 54001 Nancy Cedex, France. Electronic address: philippe.maincent@pharma.uhp-nancy.fr.
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Maincent
D000180:Acrylic Resins / Q000737:chemistry*; D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D055119:Elastic Modulus; D017984:Enoxaparin / Q000008:administration & dosage; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D017762:Nadroparin / Q000008:administration & dosage; D053758:Nanoparticles; D036103:Nanotechnology; D010539:Permeability; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D000078222:Tinzaparin; D014783:Viscosity
D000180:Acrylic Resins; D004337:Drug Carriers; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D005782:Gels; D006495:Heparin, Low-Molecular-Weight; D017762:Nadroparin; C050528:Eudragit RS; D000078222:Tinzaparin; C411345:bemiparin