Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-27T19:05:04.317Z Has data issue: false hasContentIssue false

Characterization of Polymeric Microcapsules Containing a Low Molecular Weight Peptide for Controlled Release

Published online by Cambridge University Press:  29 January 2013

Keith Moore*
Affiliation:
Biomedical Engineering Program, University of South Carolina, Columbia, SC 29209, USA
Jennifer Amos
Affiliation:
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Jeffrey Davis
Affiliation:
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
Robert Gourdie
Affiliation:
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
Jay D. Potts
Affiliation:
Biomedical Engineering Program, University of South Carolina, Columbia, SC 29209, USA Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA
*
*Corresponding author. E-mail: [email protected]
Get access

Abstract

A need exists to prolong the release of rapidly metabolized peptides of a low molecular weight, while delivering this peptide without environmental interference. Previous studies have used bovine serum albumin (BSA) as a model peptide to study release characteristics from alginate microcapsules. BSA is 66 kDa in size, while the peptide of interest here, connexin-43 carboxyl-terminus mimetic peptide (αCT1), is only 3.4 kDa. Such a change in size results in a much different set of release parameters. Our overall goal is a sustained release over a 24+ h period. Prolonged application of the peptide to a wound site to investigate therapeutic effects is ideal. As a result, a diffusion method using alginate microcapsules, along with the addition of poly-l-lysine and poly-l-ornithine, has been explored. We first aimed to establish and characterize our parameters through a set of parametric tests. Variations in polymer coating, change in pH, and changes in loading ratio have previously been shown to effect release using model compounds. Here we test specific changes in these parameters to show effects on the release of αCT1. Additionally, the microcapsules were attached to several biomaterials and surgical implants by ultraviolet cross-linking to study the effectiveness of attachment and delivery. Analysis and measurements using phase contrast microscopy, scanning electron microscopy, and atomic force microscopy were used to characterize changes in microcapsule morphology.

Type
Biological Applications
Copyright
Copyright © Microscopy Society of America 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Arghya, P., Dominique, S. & Satya, P. (2010). Investigation on PEG integrated alginate-chitosan microcapsules for myocardial therapy using marrow stem cells genetically modified by recombinant baculovirus. Cardiovasc Eng Technol 1(2), 154164.Google Scholar
Bender, J., Friedman, H., Giurgiutiu, V., Watson, C., Fitzmaurice, M. & Yost, M. (2006). The use of biomedical sensors to monitor capsule formation around soft tissue implants. Ann Plas Surg 56(1), 7277.CrossRefGoogle ScholarPubMed
Casper, C.L., Yamaguchi, N., Kiick, K.L. & Rabolt, J.F. (2005). Functionalizing electrospun fibers with biologically relevant macromolecules. Biomacromolecules 6, 19982007.CrossRefGoogle ScholarPubMed
Chakraborty, S., Liao, I., Adler, A. & Leong, K. (2009). Electrohydrodynamics: A facile technique to fabricate drug delivery systems. Adv Drug Deliver Rev 61, 10431054.CrossRefGoogle ScholarPubMed
Chew, S., Wen, J., Yim, E. & Leong, K. (2005). Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules 6, 20172024.CrossRefGoogle ScholarPubMed
Chew, S., Wen, Y., Dzenis, Y. & Leong, K. (2006). The role of electrospinning in the emerging field of nanomedicine. Current Pharm Design 12(36), 47514770.CrossRefGoogle ScholarPubMed
Choi, J., Leong, K. & Yoo, H. (2008). In vivo wound healing of diabetic ulcers using electrospun nanofibers immobilized with human epidermal growth factor (EGF). Biomaterials 29, 587596.CrossRefGoogle ScholarPubMed
Dashevsky, A. (1998). Protein loss by the microencapsulation of an enzyme (lactase) in alginate beads. Int J Pharm 161, 15.CrossRefGoogle Scholar
Draget, K., Ostgaard, K. & Smidsrod, O. (1989). Alginate-based solid media for plant tissue culture. Appl Microbiol Biotechnol 31(1), 7983.CrossRefGoogle Scholar
Enayati, M., Chang, M.-W., Bragman, F., Edirisinghe, M. & Stride, E. (2011). Electrohydrodynamic preparation of particles, capsules, and bubbles for biomedical engineering applications. Colloid Surface A 382, 154164.CrossRefGoogle Scholar
Ghatnekar, G., O'Quinn, M., Jourdan, L.J., Gurjarpadhy, A., Draughn, R. & Gourdie, R. (2009). Connexin43 carboxyl-terminal peptides reduce scar progenitor and promote regenerative healing following skin wounding. Regen Med 4(2), 205223.CrossRefGoogle ScholarPubMed
Giurgiutiu, V., Friedman, H., Bender, J., Borg, T., Yost, M., Newcomb, W., Black, A., Bost, J. & Stewart, C. (2004). Electromechanical impedance sensor for in vivo monitoring the body reaction to implants. J Invest Surg 17(5), 257270.CrossRefGoogle ScholarPubMed
Gombotz, W. & Wee, S.F. (1998). Protein release from alginate matrices. Adv Drug Deliv Rev 31, 267285.CrossRefGoogle Scholar
Gray, C.J. & Dowsett, J. (1988). Retention of insulin in alginate gel beads. Biotechnol Bioeng 31, 607612.CrossRefGoogle ScholarPubMed
Hunter, A., Barker, R., Zhu, C. & Gourdie, R. (2005). Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell 16, 56865698.CrossRefGoogle ScholarPubMed
Hwang, Y.K., Jeong, U. & Cho, E.C. (2008). Production of uniform-sized polymer core-shell microcapsules by coaxial electrospraying. Langmuir 24, 24462451.CrossRefGoogle ScholarPubMed
Katti, D.S., Robinson, K., Ko, F. & Laurencin, C. (2004). Bioresorbable nanofiber-based systems for wound healing and drug delivery: Optimization of fabrication parameters. J Biomed Mater Res B 70B, 286296.CrossRefGoogle Scholar
Langer, G. & Yamate, G. (1969). Encapsulation of liquid and solid aerosol particles to form dry powders. Colloid Interface Sci 29, 450455.CrossRefGoogle Scholar
Lin, J., Yu, W., Liu, X., Xie, H., Wang, W. & Ma, X. (2008). In vitro and in vivo characterization of alginate-chitosan-alginate artificial microcapsules for therapeutic oral delivery of live bacterial cells. J Biosci Bioeng 105(6), 660665.CrossRefGoogle ScholarPubMed
Mbanaso, E.N. & Roscoe, D.H. (1982). Alginate: An alternative to agar in plant protoblast culture. Plant Sci Lett 25(1), 6166.CrossRefGoogle Scholar
Mercade-Prieto, R., Nguyen, B., Allen, R., York, D., Preece, J., Goodwin, T. & Zhang, Z. (2011). Determination of the elastic properties of single microcapsules using micromanipulation and finite element modeling. Chem Eng Sci 66, 20422049.CrossRefGoogle Scholar
Murphy, J.A. (1980). Non-coating techniques to render biological specimens conductive. Scan Electron Microsc 1, 209220.Google Scholar
Norris, R., Moreno-Rodriguez, R., Sugi, Y., Hoffman, S., Amos, J., Hart, M., Potts, J., Goodwin, R. & Markwald, R. (2008). Periostin regulates atrioventricular valve maturation. Dev Biol 316, 200213.CrossRefGoogle ScholarPubMed
O'Quinn, M., Palatinus, J., Harris, B., Hewett, K. & Gourdie, R. (2011). A peptide mimetic of the connexin43 carboxyl terminus reduces gap junction remodeling and induced arrhythmia following ventricular injury. Circ Res 108, 704715.CrossRefGoogle ScholarPubMed
Orive, G., Tam, S., Pedraz, J. & Halle, J. (2006). Biocompatibility of alginate poly-L-lysine microcapsules for cell therapy. Biomaterials 27, 36913700.CrossRefGoogle ScholarPubMed
Oviedo-Orta, E. & Evans, W. (2004). Gap junctions and connexin-mediated communication in the immune system. Biochim Biophys Acta 1662, 102112.CrossRefGoogle ScholarPubMed
Pham, Q., Sharma, U. & Mikos, A. (2006). Electrospinning of polymeric nanofibers for tissue engineering applications: A review. Tissue Eng 12(5), 11971211.CrossRefGoogle ScholarPubMed
Rhett, J.M., Ghatnekar, G.S., Palatinus, J.A., O'Quinn, M., Yost, M. & Gourdie, R. (2008). Novel therapies for scar reduction and regenerative healing of skin wounds. Trends Biotechnol 26(4), 173180.CrossRefGoogle ScholarPubMed
Rhett, J.M., Jourdan, J. & Gourdie, R. (2011). Connexin 43 connnexon to gap junction transition is regulated by zonula occludins—1. Molec Biol Cell 22, 15161528.CrossRefGoogle Scholar
Rho, K., Jeong, L., Lee, G., Seo, B., Park, Y., Hong, S., Roh, S., Cho, J., Park, W. & Min, B. (2006). Electrospinning of collagen nanofibers: Effects on the behavior of normal human keratinocytes and early stage wound healing. Biomaterials 27, 14521461.CrossRefGoogle ScholarPubMed
Rutledge, G. & Fridrikh, S. (2007). Formation of fibers by electrospinning. Adv Drug Deliv Rev 59, 13841391.CrossRefGoogle ScholarPubMed
Takka, S. & Gurel, A. (2010). Evaluation of chitosan/alginate beads using experimental design: Formulation and in vitro characterization. AAPS PharmSciTech 11(1), 460466.CrossRefGoogle ScholarPubMed
Tama, S.K., Bilodeau, S., Dusseault, J., Langlois, G., Hallé, J.P. & Yahia, L.H. (2011). Biocompatibility and physicochemical characteristics of alginate–polycation microcapsules. Acta Biomater 7, 16831692.CrossRefGoogle Scholar
Vandenberg, G.W., Drolet, C., Scott, S.L. & de la Nouë, J. (2001). Factors affecting protein release from alginate–chitosan coacervate microcapsules during production and gastric/intestinal simulation. J Control Release 77, 297307.CrossRefGoogle ScholarPubMed
Vinkin, M., Decrock, E., Leybaert, L., Bultynck, G., Himpens, B., Vanhaecke, T. & Rogeirs, V. (2011). Non-channel functions of connexins in cell growth and cell death. Biochim Biophys Acta 8, 20022008.Google Scholar
Wan, K., Chan, V. & Dillard, D. (2002). Constitutive equation for elastic indentation of a thin-walled bio-mimetic microcapsule by an atomic force microscope tip. Colloid Surfaces B 27, 241248.CrossRefGoogle Scholar
Wu, Y., MacKay, J.A., McDaniel, J.R., Chilkoti, A. & Clark, R.L. (2009). Fabrication of elastin-like polypeptide nanoparticles for drug delivery by electrospraying. Biomacromolecules 10(1), 1924.CrossRefGoogle ScholarPubMed
Xu, Y. & Hanna, M.A. (2007). Electrosprayed bovine serum albumin-loaded tripolyphosphate cross-linked chitosan capsules: Synthesis and characterization. J Microencapsulation 24, 143151.CrossRefGoogle ScholarPubMed
Xu, Y., Skotak, M. & Hanna, M.A. (2006). Electrospray encapsulation of water-soluble protein with polylactide: Effects of formulations and process on morphology and particle size. Microencapsulation 23, 6978.CrossRefGoogle ScholarPubMed
Zhang, W. & He, X. (2009). Encapsulation of living cells in small (~100 micrometer) alginate microcapsules by electrostatic spraying: A parametric study. J Biomechanical Eng 131, 074515-1–6.CrossRefGoogle Scholar
Zhang, W., Li, B.-G., Zhang, C., Xie, X.-H. & Tang, T.-T. (2008). Biocompatibility and membrane strength of C3H10T1/2 cell-loaded alginate-based microcapsules. Cryotherapy 10(1), 9097.CrossRefGoogle ScholarPubMed
Zhang, W., Yang, G., Zhang, A., Xu, L. & He, X. (2010). Preferential vitrification of water in small alginate microcapsules significantly augments cell cryopreservation by vitrification. Biomed Microdevices 12, 8996.CrossRefGoogle ScholarPubMed
Zhao, Y., Shimizu, T., Nishihira, J., Koyama, Y., Kushibiki, T., Honda, A., Watanabe, H., Abe, R., Tabata, Y. & Shimizu, H. (2005). Tissue regeneration using macrophage migration inhibitory factor-impregnated gelatin microbeads in cutaneous wounds. Am J Pathol 167(6), 15191529.CrossRefGoogle ScholarPubMed