A new polysaccharidic gel matrix for drug delivery: preparation and mechanical properties

被引:48
作者
Coviello, T
Alhaique, F
Parisi, C
Matricardi, P
Bocchinfuso, G
Grassi, M
机构
[1] Univ Roma La Sapienza, Dipartimento Studi Chim & Tecnol, Sostanze Biol Attive, I-00185 Rome, Italy
[2] Univ Roma Tor Vergata, Dipartimento Sci & Tecnol Chim, I-00133 Rome, Italy
[3] Univ Trieste, Dipartimento Ingn Chim, Ambiente Mat Prime, I-34127 Trieste, Italy
关键词
scleroglucan derivative; hydrogel; theophylline; myoglobin; modified release; texture analyzer;
D O I
10.1016/j.jconrel.2004.10.028
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A new type of hydrogel was prepared, under controlled conditions, by diffusion of Ca(II) ions into a solution of the carboxylated derivative of Scleroglucan (Sclerox). The obtained hydrogel was loaded with Theophylline (TPH) and Myoglobin (MGB), two model drugs of remarkably different steric hindrance, and also used, after freeze drying, for the preparation of tablets. Release studies were carried out on both the freshly prepared gel and on the tablets. As far as the gel systems experiments are concerned, the delivery profiles resulted to be deeply dependent on the molecular dimensions of the loaded molecules; TPH was easily released while the larger tested molecule (MGB) remained partially entrapped within the three-dimensional network. Furthermore, in the case of MGB, the release was dependent also on polymer concentration (c(p)): at the highest investigated cp value a corresponding lowest delivery of the guest molecule was observed. This effect of polymer concentration on the rate of delivery was studied applying three different mathematical approaches: the one that better fitted the experimental release profile allowed to support the explanation of the mechanism involved in the observed two-step delivery that has been related to the drug trapping inside the clusters of the gel network. The delivery profiles from the tablets showed how the release, in this case, could be related, essentially, to the molecular dimensions of the guest molecules, independently on the cp used to prepare the starting hydrogel. TPH was completely delivered in a few hours while the MGB was almost unable to diffuse out of the matrix and more than 80% resulted entrapped in the network for at least 24 h. The novel hydrogel, at different c(p), was also characterized by means of a texture analyzer to inspect its mechanical properties. According to the compression data, the hardness, the work of cohesion and the work of adhesion of the networks were estimated. Furthermore, by means of relaxation experiments, analysed applying the generalized Maxwell model, the gels can be classified as solid viscoelastic materials and the mechanical spectra indicated a predominance of the viscous behaviour, while the Young modulus, E-0, as expected, was found to increase with polymer concentration. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:643 / 656
页数:14
相关论文
共 39 条
[1]  
Alhaique F, 1990, Drug Des Deliv, V5, P249
[2]   Phase equilibria and mechanical properties of gel-like water-gelatin-locust bean gum systems [J].
Alves, MM ;
Antonov, YA ;
Gonçalves, MP .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2000, 27 (01) :41-47
[3]   SOLID-STATE AND SOLUTION CONFORMATION OF SCLEROGLUCAN [J].
BLUHM, TL ;
DESLANDES, Y ;
MARCHESSAULT, RH ;
PEREZ, S ;
RINAUDO, M .
CARBOHYDRATE RESEARCH, 1982, 100 (MAR) :117-130
[4]   CRITICAL ASSOCIATION AND THERMOREVERSIBLE GELATION OF SOME SELECTED POLYMERS [J].
BURCHARD, W ;
LANG, P ;
SCHULZ, L ;
COVIELLO, T .
MAKROMOLEKULARE CHEMIE-MACROMOLECULAR SYMPOSIA, 1992, 58 :21-37
[5]   Structure formation by polysaccharides in concentrated solution [J].
Burchard, W .
BIOMACROMOLECULES, 2001, 2 (02) :342-353
[6]  
CLARK AH, 1987, ADV POLYM SCI, V83, P57
[7]   Static and dynamic light scattering by a thermoreversible gel from Rhizobium leguminosarum 8002 exopolysaccharide [J].
Coviello, T ;
Burchard, W ;
Geissler, E ;
Maier, D .
MACROMOLECULES, 1997, 30 (07) :2008-2015
[8]   Structural and rheological characterization of Scleroglucan/borax hydrogel for drug delivery [J].
Coviello, T ;
Coluzzi, G ;
Palleschi, A ;
Grassi, M ;
Santucci, E ;
Alhaique, F .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2003, 32 (3-5) :83-92
[9]   Scleroglucan/borax: characterization of a novel hydrogel system suitable for drug delivery [J].
Coviello, T ;
Grassi, M ;
Lapasin, R ;
Marino, A ;
Alhaique, F .
BIOMATERIALS, 2003, 24 (16) :2789-2798
[10]   IONIC-STRENGTH AND TEMPERATURE-DEPENDENCE OF OXIDIZED SCLEROGLUCAN SOLUTION PROPERTIES - OPTICAL-ACTIVITY AND VISCOSITY DATA [J].
COVIELLO, T ;
DENTINI, M ;
CRESCENZI, V ;
VINCENTI, A .
CARBOHYDRATE POLYMERS, 1995, 26 (01) :5-10