Collagen containing microcapsules: smart containers for disease controlled therapy.

The protein collagen is the major component of connective tissue and it is involved in many biological functions. Its degradation is at the basis of different pathological processes. The up-regulated expression of matrix metalloproteinases and the down-regulated expression of their inhibitors are the causes for such degradation. The aim of this work was to evaluate the possibility to fabricate collagen based containers for drug encapsulation and release by cellular demand by the action of matrix metalloproteinases. In present work collagen type I based microcapsules were fabricated by means of the layer-by-layer assembly of oppositely charged collagen and poly (stirene sulfonate) onto colloidal particles, followed by removal of the cores to obtain hollow microcapsules. The process of shell growth on planar supports was monitored by quartz crystal microbalance. X-ray reflectivity measurements were carried out at the solid/water interface to study the interaction of matrix metalloproteinase 1 with LbL films of collagen. The morphology of hollow capsules was characterized by scanning electron microscopy, and compared to that of capsules exposed to the matrix metalloproteinase 1. Finally the matrix metalloproteinase 1 mediated permeability of capsules variation was studied by Confocal Laser Scanning Microscopy. The results demonstrated the possibility to fabricate a drug delivery system where the release of the drug is dependent on the biochemistry of the pathological state.

[1]  Y. Lvov,et al.  Nano-encapsulation of furosemide microcrystals for controlled drug release. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[2]  H. Möhwald,et al.  Sustained release properties of polyelectrolyte multilayer capsules. , 2001 .

[3]  T. Kawamoto,et al.  Enhancement of cartilage matrix protein synthesis in arthritic cartilage. , 1997, Arthritis and rheumatism.

[4]  A. Zaninelli,et al.  Osteoarthritis: an overview of the disease and its treatment strategies. , 2005, Seminars in arthritis and rheumatism.

[5]  S. J. Martin,et al.  Modeling the Responses of Thickness-Shear Mode Resonators under Various Loading Conditions. , 1999, Analytical chemistry.

[6]  Gleb B. Sukhorukov,et al.  Stepwise Polyelectrolyte Assembly on Particle Surfaces: a Novel Approach to Colloid Design , 1998 .

[7]  Ponisseril Somasundaran,et al.  ENCYCLOPEDIA OF Surface and Colloid Science , 2006 .

[8]  Stephen J. Martin,et al.  Characterization of a quartz crystal microbalance with simultaneous mass and liquid loading , 1991 .

[9]  Y. Lvov,et al.  (-)-Epigallocatechin gallate/gelatin layer-by-layer assembled films and microcapsules. , 2009, Journal of colloid and interface science.

[10]  H. Möhwald,et al.  Multifunctional cargo systems for biotechnology. , 2007, Trends in biotechnology.

[11]  C. Dupont-Gillain,et al.  Synthesis of collagen nanotubes with highly regular dimensions through membrane-templated layer-by-layer assembly. , 2009, Biomacromolecules.

[12]  Gero Decher,et al.  Toward Layered Polymeric Multicomposites , 1997 .

[13]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[14]  F. Caruso,et al.  Enzyme encapsulation in layer-by-layer engineered polymer multilayer capsules. , 2000 .

[15]  H. Mark,et al.  Encyclopedia of polymer science and engineering , 1985 .

[16]  R. Iler,et al.  Multilayers of colloidal particles , 1966 .

[17]  Nicholas A. Kotov,et al.  Layer-By-Layer Assembly of Collagen Thin Films: Controlled Thickness and Biocompatibility , 2001 .

[18]  Tim Liedl,et al.  Nanoengineered polymer capsules: tools for detection, controlled delivery, and site-specific manipulation. , 2005, Small.

[19]  H. Möhwald,et al.  Hollow polyelectrolyte shells: Exclusion of polymers and Donnan equilibrium. , 1999 .

[20]  B. Clarke.  Dynamics of Bone and Cartilage Metabolism , 2000 .

[21]  T. Berzina,et al.  X-ray reflectivity measurements of layer-by-layer films at the solid/liquid interface. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[22]  M. Fontana,et al.  Light-driven release from polymeric microcapsules functionalized with bacteriorhodopsin. , 2009, Journal of the American Chemical Society.

[23]  T. Viitala,et al.  Structure of anionic phospholipid coatings on silica by dissipative quartz crystal microbalance. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[24]  M. Stamm,et al.  Formation of silver islands on Langmuir-Blodgett films as investigated by x-ray reflectometry , 1992 .

[25]  Gero Decher,et al.  Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites , 1997 .

[26]  J. Bilezikian,et al.  Dynamics of bone and cartilage metabolism , 1999 .

[27]  F. Caruso,et al.  Biocolloids with ordered urease multilayer shells as enzymatic reactors. , 2001, Analytical chemistry.

[28]  Carmelina Ruggiero,et al.  Paclitaxel-containing nano-engineered polymeric capsules towards cancer therapy. , 2009, Journal of nanoscience and nanotechnology.

[29]  H. Nagase,et al.  Progress in matrix metalloproteinase research. , 2008, Molecular aspects of medicine.

[30]  S. Gay,et al.  Proteinases in the joint: clinical relevance of proteinases in joint destruction , 2007, Arthritis research & therapy.

[31]  K. Kjaer,et al.  Influence of ether linkages on the structure of double-chain phospholipid monolayers , 1995 .

[32]  Caruso,et al.  Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating , 1998, Science.

[33]  Helmuth Möhwald,et al.  Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes. , 1998, Angewandte Chemie.

[34]  M. Selman,et al.  MMP-1: the elder of the family. , 2005, The international journal of biochemistry & cell biology.