Biodegradable polymeric microcapsules: Preparation and properties

Biodegradable polymeric microcapsules can be produced through different methods of which emulsion solvent-evaporation/extraction is frequently used. In this technique, the polymer (often polylactide) is dissolved in a good solvent and is emulsified together with a poor solvent into a nonsolvent phase. The solvent is then removed through the nonsolvent phase by evaporation. This results in solidification of the polymer around an internal droplet of the poor solvent. The poor solvent may be removed later when hollow capsules are required. This paper discusses the fundamental aspects of the formation process of hollow polylactide microcapsules and its effects on the physical and chemical properties of the capsules, with emphasis on the solidification process of the polymer and the resulting properties of the shell. The scope for improvement and adaptation of the current process, including new emulsification techniques, is also discussed. The main message of this paper is that the properties of the capsules can be optimized through the solidification process of the polymer which can be highly influenced by the proper choice of the nonsolvent and oil. Since this field is hardly investigated in literature, there is room for improvement, especially if the capsules can be produced with the newest emulsification technologies that are becoming available.

[1]  B. Wesslén,et al.  Preparation and properties of plasticized poly(lactic acid) films. , 2005, Biomacromolecules.

[2]  S. Sosnowski Poly(L-lactide) microspheres with controlled crystallinity , 2001 .

[3]  Alexander L. Klibanov,et al.  Microbubble Contrast Agents: Targeted Ultrasound Imaging and Ultrasound-Assisted Drug-Delivery Applications , 2006, Investigative radiology.

[4]  M. H. Santana,et al.  THE EFFECT OF SOME PROCESSING CONDITIONS ON THE CHARACTERISTICS OF BIODEGRADABLE MICROSPHERES OBTAINED BY AN EMULSION SOLVENT EVAPORATION PROCESS , 2004 .

[5]  Remko M. Boom,et al.  Droplet formation in a T-shaped microchannel junction: A model system for membrane emulsification , 2005 .

[6]  H. Fritz,et al.  Plasticizing polylactide—the effect of different plasticizers on the mechanical properties , 1999 .

[7]  I. Chronakis,et al.  Biodegradable films of partly branched poly(l-lactide)-co-poly(epsilon-caprolactone) copolymer: modulation of phase morphology, plasticization properties and thermal depolymerization. , 2004, Biomacromolecules.

[8]  A. Albertsson,et al.  Morphology engineering of a novel poly(L-lactide)/poly(1,5-dioxepan-2-one) microsphere system for controlled drug delivery , 2000 .

[9]  Krzysztof Pielichowski,et al.  Polymer/montmorillonite nanocomposites with improved thermal properties Part I. Factors influencing thermal stability and mechanisms of thermal stability improvement , 2007 .

[10]  V. Torchilin,et al.  Biodegradable long-circulating polymeric nanospheres. , 1994, Science.

[11]  M. Jonkman,et al.  Reinforced poly(L-lactic acid) fibres as suture material. , 1995, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[12]  E. Sudhölter,et al.  Covalently attached saccharides on silicon surfaces. , 2003, Journal of the American Chemical Society.

[13]  B. C. Thanoo,et al.  Effect of solvent removal technique on the matrix characteristics of polylactide/glycolide microspheres for peptide delivery , 1996 .

[14]  K. Schroën,et al.  Covalent attachment of organic monolayers to silicon carbide surfaces. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[15]  Hans P Merkle,et al.  Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Ryutaro Maeda,et al.  Straight-through microchannel devices for generating monodisperse emulsion droplets several microns in size , 2008 .

[17]  Ji Song,et al.  Influence of microbubble shell properties on ultrasound signal: Implications for low-power perfusion imaging. , 2002, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[18]  Karin Schroën,et al.  Parallelized edge-based droplet generation (EDGE) devices. , 2009, Lab on a chip.

[19]  A. Häkkinen,et al.  The effect of cosolvents on the formulation of nanoparticles from low-molecular-weight poly(I)lactide , 2002, AAPS PharmSciTech.

[20]  Byung-Soo Kim,et al.  Thermally produced biodegradable scaffolds for cartilage tissue engineering. , 2004, Macromolecular bioscience.

[21]  G. Ma,et al.  Study of the preparation and mechanism of formation of hollow monodisperse polystyrene microspheres by SPG (Shirasu Porous Glass) emulsification technique , 2002 .

[22]  Yi Yan Yang,et al.  Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method , 2000 .

[23]  Paul A Dayton,et al.  Tailoring the Size Distribution of Ultrasound Contrast Agents: Possible Method for Improving Sensitivity in Molecular Imaging , 2007, Molecular imaging.

[24]  R. Boom,et al.  Why liquid displacement methods are sometimes wrong in estimating the pore‐size distribution , 2004 .

[25]  L. Cheng,et al.  Mechanisms of PVDF membrane formation by immersion-precipitation in soft (1-octanol) and harsh (water) nonsolvents , 1999 .

[26]  Ernst J. R. Sudhölter,et al.  Amino-Terminated Organic Monolayers on Hydrogen-Terminated Silicon Surfaces , 2001 .

[27]  P. Kleinebudde,et al.  Residual solvents in biodegradable microparticles. Influence of process parameters on the residual solvent in microparticles produced by the aerosol solvent extraction system (ASES) process. , 1997, Journal of pharmaceutical sciences.

[28]  J Mühling,et al.  Poly(L-lactide): a long-term degradation study in vivo. Part III. Analytical characterization. , 1993, Biomaterials.

[29]  M. Nagai,et al.  Preparation of uniform poly(lactide) microspheres by employing the Shirasu Porous Glass (SPG) emulsification technique , 1999 .

[30]  C. Zavaglia,et al.  Synthesis and characterization of poly(L-lactic acid) membranes: Studies in vivo and in vitro , 2003, Journal of materials science. Materials in medicine.

[31]  Amar K. Mohanty,et al.  Effect of the processing methods on the performance of polylactide films: Thermocompression versus solvent casting , 2006 .

[32]  T. Nisisako,et al.  Microfluidic large-scale integration on a chip for mass production of monodisperse droplets and particles. , 2008, Lab on a chip.

[33]  Karin Schroën,et al.  Tailor-made functionalization of silicon nitride surfaces. , 2004, Journal of the American Chemical Society.

[34]  M. Nagai,et al.  Preparation and analysis of uniform emulsion droplets using SPG membrane emulsification technique , 2000 .

[35]  A. Göpferich,et al.  Mechanisms of polymer degradation and erosion. , 1996, Biomaterials.

[36]  M. Wheatley,et al.  Development of a novel method for synthesis of a polymeric ultrasound contrast agent. , 2003, Journal of biomedical materials research. Part A.

[37]  P. Sinko,et al.  The effect of physical barriers and properties on the oral absorption of particulates. , 1998, Advanced drug delivery reviews.

[38]  J. Pikkemaat,et al.  Preparation of monodisperse polymer particles and capsules by ink-jet printing , 2006 .

[39]  Ajit Raisinghani,et al.  Physical principles of microbubble ultrasound contrast agents. , 2002, The American journal of cardiology.

[40]  M. Wheatley,et al.  Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[41]  R. Boom,et al.  Recent advances in the formation of phase inversion membranes made from amorphous or semi-crystalline polymers , 1996 .

[42]  Ronni Wolf,et al.  Percutaneous absorption and delivery systems3 , 2001 .

[43]  Olivier Rouaud,et al.  Microencapsulation by solvent evaporation: state of the art for process engineering approaches. , 2008, International journal of pharmaceutics.

[44]  R. Boom,et al.  Addition of Oils to Polylactide Casting Solutions as a Tool to Tune Film Morphology and Mechanical Properties , 2010 .

[45]  Goran T Vladisavljević,et al.  Recent developments in manufacturing emulsions and particulate products using membranes. , 2005, Advances in colloid and interface science.

[46]  Sumie Yoshioka,et al.  Preparation of poly(l-lactide) microspheres of different crystalline morphology and effect of crystalline morphology on drug release rate , 1991 .

[47]  L. Cheng,et al.  Formation of crystalline EVAL membranes by controlled mass transfer process in water–DMSO–EVAL copolymer systems , 1998 .

[48]  X. Zhu,et al.  Polymer microspheres for controlled drug release. , 2004, International journal of pharmaceutics.

[49]  A. Coombes,et al.  A novel emulsification-solvent extraction technique for production of protein loaded biodegradable microparticles for vaccine and drug delivery , 1995 .

[50]  T. Park,et al.  Comparative study on sustained release of human growth hormone from semi-crystalline poly(L-lactic acid) and amorphous poly(D,L-lactic-co-glycolic acid) microspheres: morphological effect on protein release. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[51]  L. Avérous,et al.  Poly(lactic acid): plasticization and properties of biodegradable multiphase systems , 2001 .

[52]  E Fattal,et al.  Polymeric nano/microcapsules of liquid perfluorocarbons for ultrasonic imaging: physical characterization. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[53]  P. Mozetic,et al.  Polymer Microbubbles As Diagnostic and Therapeutic Gas Delivery Device , 2008 .

[54]  Frank Caruso,et al.  Layer-by-layer engineered capsules and their applications , 2006 .

[55]  S. Homma,et al.  Effect of microbubble size on fundamental mode high frequency ultrasound imaging in mice. , 2010, Ultrasound in medicine & biology.

[56]  P. Seib,et al.  Blending of poly(lactic acid) and starches containing varying amylose content , 2003 .

[57]  M. Wheatley,et al.  Polymeric contrast agent with targeting potential. , 2004, Ultrasonics.

[58]  Sugiura,et al.  Preparation of Monodispersed Solid Lipid Microspheres Using a Microchannel Emulsification Technique. , 2000, Journal of colloid and interface science.

[59]  J Mühling,et al.  Poly(L-lactide): a long-term degradation study in vivo. I. Biological results. , 1993, Biomaterials.

[60]  R. Boom,et al.  Polylactide films formed by immersion precipitation: Effects of additives, nonsolvent, and temperature , 2007 .

[61]  M. Cima,et al.  Carbon dioxide extraction of residual chloroform from biodegradable polymers. , 2002, Journal of biomedical materials research.

[62]  M. Wheatley,et al.  Ultrasound degradation of novel polymer contrast agents. , 2004, Journal of biomedical materials research. Part A.

[63]  Nico de Jong,et al.  High-speed optical observations of contrast agent destruction. , 2005, Ultrasound in medicine & biology.

[64]  Remko M. Boom,et al.  Preparation of hollow polylactide microcapsules through premix membrane emulsification-Effects of nonsolvent properties , 2008 .

[65]  C. A. Smolders,et al.  Diffusion induced phase separation with crystallizable nylons. II. Relation to final membrane morphology , 1996 .

[66]  R. Guy,et al.  Ultrasound-mediated gene delivery: influence of contrast agent on transfection. , 2007, Bioconjugate chemistry.

[67]  L. Lim,et al.  Processing technologies for poly(lactic acid) , 2008 .

[68]  P. Grayburn Current and Future Contrast Agents , 2002, Echocardiography.

[69]  R. Gross,et al.  Citrate esters as plasticizers for poly(lactic acid) , 1997 .

[70]  A. Loxley,et al.  Preparation of Poly(methylmethacrylate) Microcapsules with Liquid Cores. , 1998, Journal of colloid and interface science.

[71]  R. Boom,et al.  Hollow polylactide microcapsules with controlled morphology and thermal and mechanical properties , 2009 .

[72]  Eleanor Stride,et al.  Novel microbubble preparation technologies , 2008 .

[73]  C. A. Smolders,et al.  Formation of membranes by means of immersion precipitation : Part II. the mechanism of formation of membranes prepared from the system cellulose acetate-acetone-water , 1987 .

[74]  R. Boom,et al.  Influence of dynamic interfacial tension on droplet formation during membrane emulsification. , 2004, Journal of colloid and interface science.

[75]  Suming Li,et al.  Hydrolytic degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. , 1999 .

[76]  A. Hiltner,et al.  Aging of poly(lactide)/poly(ethylene glycol) blends. Part 2. Poly(lactide) with high stereoregularity , 2003 .

[77]  Soojin Park,et al.  Preparation and characterization of biodegradable poly(l-lactide)/poly(ethylene glycol) microcapsules containing erythromycin by emulsion solvent evaporation technique. , 2004, Journal of colloid and interface science.

[78]  T. Randolph,et al.  Process Variable Implications for Residual Solvent Removal and Polymer Morphology in the Formation of Gentamycin-Loaded Poly (L-lactide) Microparticles , 1998, Pharmaceutical Research.

[79]  R. Boom,et al.  Polylactide microspheres prepared by premix membrane emulsification—Effects of solvent removal rate , 2008 .

[80]  R. Boom,et al.  Mechanical properties and porosity of polylactide for biomedical applications , 2008 .

[81]  J.W.A. van den Berg,et al.  Phase behavior of polylactides in solvent–nonsolvent mixtures , 1996 .

[82]  M. L. Ferreira,et al.  PLA nano- and microparticles for drug delivery: an overview of the methods of preparation. , 2007, Macromolecular bioscience.

[83]  W. Shi,et al.  Effect of molecular weight, crystallinity, and hydrophobicity on the acoustic activation of polymer-shelled ultrasound contrast agents. , 2009, Biomacromolecules.

[84]  Nico de Jong,et al.  Oil-filled polymer microcapsules for ultrasound-mediated delivery of lipophilic drugs. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[85]  Stephen P. McCarthy,et al.  Biodegradable polymer blends of poly(lactic acid) and poly(ethylene glycol) , 1997 .

[86]  Jan Feijen,et al.  Phase-Separation Processes in Polymer-Solutions in Relation to Membrane Formation , 1996 .

[87]  S. Nakao,et al.  Preparation of Micron-Sized Monodispersed Thermoresponsive Core−Shell Microcapsules , 2002 .

[88]  C. F. van der Walle,et al.  Engineering biodegradable polyester particles with specific drug targeting and drug release properties. , 2008, Journal of pharmaceutical sciences.

[89]  S. Verma,et al.  Fast degradable poly(L‐lactide‐co‐ε‐caprolactone) microspheres for tissue engineering: Synthesis, characterization, and degradation behavior , 2007 .

[90]  G. Ma,et al.  Preparation of uniform-sized PLA microcapsules by combining Shirasu porous glass membrane emulsification technique and multiple emulsion-solvent evaporation method. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[91]  Goran T. Vladisavljevic,et al.  Preparation and analysis of oil-in-water emulsions with a narrow droplet size distribution using Shirasu-porous-glass (SPG) membranes☆ , 2002 .

[92]  E. Drioli,et al.  New PVDF microcapsules for application in catalysis , 2008 .

[93]  Susan Selke,et al.  An overview of polylactides as packaging materials. , 2004, Macromolecular bioscience.

[94]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.