Macromolecular composition and drug-loading effect on the delivery of paclitaxel and folic acid from acrylic matrices

Drug delivery systems based on synthetic polymers are widely employed in the treatment of several pathologies. In particular, the use of implantable devices able to release one or more active principles in a topic site with a controlled delivery kinetic represents an important improvement in this field. However, the release kinetic, that could be affected by different parameters, like polymer composition or chemical nature and initial drug loading, represents one of the problems related to the implantation of delivery systems. In this study, acrylic membranes with different macromolecular composition were prepared and studied analyzing delivery kinetic properties. Drug delivery systems were prepared using as matrix the copolymer poly(methylmethacrylate-co-butylmethacrylate) in three different compositions and folic acid (less hydrophobic) or Paclitaxel (more hydrophobic) as drugs, to evaluate the effect of macromolecular composition and hydrophilicity degree on the release properties. In addition, the effect of the initial drug loading was considered, loading drug delivery systems with four different initial drug percentages. Results showed a direct dependence of kinetics from macromolecular composition, hydrophilicity degree of solutes, and initial drug loading, allowing one to conclude that it is possible to design and to develop drug delivery systems starting from poly(methylmethacrylate-co-butylmethacrylate) matrices with specific properties by varying these three parameters.

[1]  G. Ciardelli,et al.  Acrylic Copolymers as Candidates for Drug-Eluting Coating of Vascular Stents , 2009, Journal of biomaterials applications.

[2]  C. Allen,et al.  Block copolymer micelles for delivery of cancer therapy: transport at the whole body, tissue and cellular levels. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[3]  D. Chiappetta,et al.  Drug delivery systems in HIV pharmacotherapy: what has been done and the challenges standing ahead. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[4]  C. Peterson,et al.  Drug delivery for in vitro fertilization: rationale, current strategies and challenges. , 2009, Advanced drug delivery reviews.

[5]  K. Fowers,et al.  OncoGel (ReGel/paclitaxel)--clinical applications for a novel paclitaxel delivery system. , 2009, Advanced drug delivery reviews.

[6]  Shri Kant,et al.  Polymeric nanoparticulate system: a potential approach for ocular drug delivery. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[7]  P. Giusti,et al.  Different composition poly(methyl methacrylate-co-butyl methacrylate) copolymers through seeded semi-batch emulsion polymerization , 2009 .

[8]  Qingbing Zeng,et al.  Poly(lactide-co-glycolide) nanoparticles as carriers for norcantharidin , 2009 .

[9]  K. Neoh,et al.  Synthesis of Folic Acid Functionalized PLLA-b-PPEGMA Nanoparticles for Cancer Cell Targeting. , 2009, Macromolecular rapid communications.

[10]  Can Zhang,et al.  Water‐soluble poly(ethylene glycol) prodrug of pemetrexed: Synthesis, characterization, and preliminary cytotoxicity , 2009 .

[11]  P. Giusti,et al.  Synthesis and characterization of copolymers of methylmethacrylate and 2-hydroxyethyl methacrylate for the aqueous solubilization of Paclitaxel. , 2009, Drug Delivery.

[12]  M. Stevanović,et al.  Poly(DL-lactide-co-glycolide) Nanospheres for the Sustained Release of Folic Acid , 2008 .

[13]  Dianrui Zhang,et al.  Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system , 2008 .

[14]  David L Kaplan,et al.  Controlled release from multilayer silk biomaterial coatings to modulate vascular cell responses. , 2008, Biomaterials.

[15]  M. Johnston,et al.  A novel trans-lymphatic drug delivery system: implantable gelatin sponge impregnated with PLGA-paclitaxel microspheres. , 2007, Biomaterials.

[16]  J. Filipović,et al.  Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation , 2007 .

[17]  M. Setou,et al.  Cellular recognition of functionalized with folic acid nanoparticles , 2007 .

[18]  Kazunori Kataoka,et al.  Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. , 2006, Pharmacology & therapeutics.

[19]  C. Allen,et al.  Formulation of drugs in block copolymer micelles: drug loading and release. , 2006, Current pharmaceutical design.

[20]  V. Torchilin,et al.  Targeted polymeric micelles for delivery of poorly soluble drugs , 2004, Cellular and Molecular Life Sciences CMLS.

[21]  Alex Sparreboom,et al.  Role of Formulation Vehicles in Taxane Pharmacology , 2001, Investigational New Drugs.

[22]  P. Costa,et al.  Influence of Dissolution Medium Agitation on Release Profiles of Sustained-Release Tablets , 2001 .

[23]  M. R. Mejillano,et al.  Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity. , 1992, Journal of medicinal chemistry.

[24]  N. R. Pallas,et al.  An automated drop shape apparatus and the surface tension of pure water , 1990 .

[25]  Nicholas A. Peppas,et al.  A simple equation for description of solute release II. Fickian and anomalous release from swellable devices , 1987 .

[26]  Nicholas A. Peppas,et al.  A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs , 1987 .

[27]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[28]  T. Higuchi MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.