title: Drug release mechanisms of chemically cross-linked albumin microparticles: effect of the matrix erosion.
abstract: Albumin (BSA) microparticles were developed as a biotechnological alternative for drug delivery. Vitamin B12 (Vit-B12) was used as a model drug. The microparticles were obtained from maleic anhydride-functionalized BSA and N',N'-dimethylacrylamide (DMAAm) in a W/O emulsion without and with PVA. The microparticles produced at 15min of stirring without PVA showed the best results in terms of size, homogeneity, and sphericity. In such a case, BSA played a role as a surface active agent, replacing PVA. For longer stirring times, BSA was unable to act as an emulsifier. These microparticles showed an uncommon release profile, consisting of a two-step release mechanism, at the pH range studied. Considering that a two-step release mechanism is occurring, the experimental data were adjusted by applying modified power law and Weibull equations in order to describe release mechanism n and release rate constant k, respectively. Each one of the release stages was related to a specific value of n and k. The second stage was driven by a super case II transport mechanism, as a result of diffusion, macromolecular relaxation, and erosion. A third model, described by Hixson-Crowell, confirmed the erosion mechanism. Vit-B12 diffusion kinetics in aqueous solutions (i.e., without the microparticles) follows a one-step process, being k dependent on the pH, confirming that the two-step release mechanism is a characteristic profile of the developed microparticles. The microparticles released only 2.70% of their initial drug load at pH 2, and 58.53% at pH 10.
authors.affiliation: Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Danielly L A
authors.initials: DLA
authors.lastname: Sitta
authors.affiliation: Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Guilherme
authors.affiliation: Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Elisangela P
authors.initials: EP
authors.lastname: da Silva
authors.affiliation: Department of Chemistry, University of Coimbra, Coimbra 3004 535, Portugal.
authors.forename: Artur J M
authors.initials: AJM
authors.lastname: Valente
authors.affiliation: Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, Paraná, Brazil.
authors.forename: Edvani C
authors.initials: EC
authors.lastname: Muniz
authors.affiliation: Department of Chemistry, State University of Maringá, Av. Colombo, 5790, CEP 87020-900, Maringá, Paraná, Brazil. Electronic address: afrubira@uem.br.
authors.forename: Adley F
authors.initials: AF
authors.lastname: Rubira
mesh_terms: D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D066244:Proton Magnetic Resonance Spectroscopy; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014805:Vitamin B 12 / Q000493:pharmacokinetics
chemical_list: D012710:Serum Albumin, Bovine; D014805:Vitamin B 12
keywords: Albumin; Drug delivery; Drug release kinetics; Emulsion; Erosion; Microparticles