title: Polymeric Nanoparticles of Enoxaparin as a Delivery System: In Vivo Evaluation in Normal Rats and in a Venous Thrombosis Rat Model.
abstract: Enoxaparin is an anticoagulant widely used in the treatment and prophylaxis of deep vein thrombosis (DVT). The subcutaneous route of administration, sometimes in repeated doses during 24 hours, represents a limitation to its use. Thus, the development of a product that can be administered either subcutaneously, in a smaller number of applications becomes a major challenge, with interesting clinical applications. The use of a system for sustained release of drugs can help to meet that goal, by protecting and enabling a gradual released of the agent. This study consisted of the evaluation of in vivo anticoagulant and antithrombotic activity of biodegradable nanoparticles of poly (ε-caprolactone) (PCL) with enoxaparin after subcutaneous injection. The nanoparticles were prepared by the method of double emulsion (w/o/w) and solvent evaporation. Subcutaneous enoxaparin encapsulated in PCL nanoparticles (1000 IU/kg) showed a sustained release in vivo for up to 12 hours (Cmax 0.62 IU/mL) a significantly longer period (P < 0.01) when compared to free enoxaparin (1000 IU/Kg) that disappeared after 9 hours (Cmax 1.50 IU/mL), however with lower anti-Xa activity. The antithrombotic action of enoxaparin-nanoparticles was tested in a DVT model by stasis in rats. There were virtually no formation of venous thrombosis in any of the rats that received enoxaparin encapsulated in nanoparticles (0.03 mg), with a significant difference when compared to groups that received saline (17.2 mg, P < 0.001) and free enoxaparin (2.87 mg, P = 0.001). In summary, enoxaparin-encapsulated in polymeric nanoparticles showed a sustained release for a greater period than that of enoxaparin, and with excellent antithrombotic action. These results corroborate the promising use of pharmacological nanoparticles in clinical practice.
authors.forename: Carla
authors.initials: C
authors.lastname: Pazzini
authors.forename: Priscyla D
authors.initials: PD
authors.lastname: Marcato
authors.forename: Lucas Bessa
authors.initials: LB
authors.lastname: Prado
authors.forename: Aline Morandi
authors.initials: AM
authors.lastname: Alessio
authors.forename: Nelci Fenalt
authors.initials: NF
authors.lastname: Höehr
authors.forename: Silmara
authors.initials: S
authors.lastname: Montalvão
authors.forename: Devanira
authors.initials: D
authors.lastname: Paixão
authors.forename: Nelson
authors.initials: N
authors.lastname: Durán
authors.forename: Joyce Maria
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D017984:Enoxaparin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011091:Polyesters; C016240:polycaprolactone