Modeling diffusion-based drug release inside a nerve conduit in vitro and in vivo validation study.


Journal

Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061

Informations de publication

Date de publication:
02 2021
Historique:
pubmed: 6 5 2020
medline: 26 11 2021
entrez: 6 5 2020
Statut: ppublish

Résumé

The objective of this work was to develop a model and understand the diffusion of a drug into and throughout a drug delivering nerve conduit from a surrounding reservoir through a hole in the wall separating the lumen of the conduit and the reservoir. A mathematical model based on Fick's law of diffusion was developed using the finite difference method to understand the drug diffusion and the effect of varying device parameters on the concentration of drug delivered from a hole-based drug delivery device. The mathematical model was verified using a physical microfluidic (μFD) model and an in vitro/in vivo release test using prototype devices. The results of the mathematical model evaluation and microfluidic device testing offered positive insight into the reliability and function of the reservoir and hole-based drug delivering nerve conduit. The mathematical model demonstrated how changing device parameters would change the drug concentration inside the device. It was observed that the drug release in the conduit could be tuned by both concentration scaling and changing the hole size or number of holes. Based on the results obtained from the microfluidic device, the error in the mathematical drug release model was shown to be less than 10% when comparing the data obtained from mathematical model and μFD model. The data highlights the flexibility of having a hole-based drug delivery system, since the drug release can be scaled predictably by changing the device parameters or the concentration of the drug in the reservoir. Graphical abstract .

Identifiants

pubmed: 32367424
doi: 10.1007/s13346-020-00755-y
pii: 10.1007/s13346-020-00755-y
doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

154-168

Références

Navarro X, Udina E, Ceballos D, Gold BG. Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps. Muscle Nerve. 2001;24:905–15.
pubmed: 11410918
Udina E, Gold BG, Navarro X. Comparison of continuous and discontinuous FK506 administration on autograft or allograft repair of sciatic nerve resection. Muscle Nerve. 2004;29:812–22.
pubmed: 15170614
Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Ann Rev. Neurosci. 2001;24:677–736.
pubmed: 11520916
Frostick SP, Yin Q, Kemp GJ. Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurg. 1998;18:397–405.
Giger RJ, Hollis ER, Tuszynski MH. Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol. 2010;2:a001867.
pubmed: 20519341 pmcid: 2890195
Zhou FQ, Snider WD. Intracellular control of developmental and regenerative axon growth. Philos Trans R Soc Lond Ser B Biol Sci. 2006;361:1575–92.
De Boer R, Knight AM, Borntraeger A, Hébert-Blouin M, Spinner RJ, Malessy MJ, et al. Rat sciatic nerve repair with a poly-lactic-co-glycolic acid scaffold and nerve growth factor releasing microspheres. Microsurg. 2011;31:293–302.
Wang Z, Han N, Wang J, Zheng H, Peng J, Kou Y, et al. Improved peripheral nerve regeneration with sustained release nerve growth factor microspheres in small gap tubulization. Am J Transl Res. 2014;6(4):413–21.
pubmed: 25075258 pmcid: 4113503
Manoukian OS, Arul MR, Rudraiah S, Kalajzic I, Kumbar SG. Aligned microchannel polymer-nanotube composites for peripheral nerve regeneration: small molecule drug delivery. J Control Release. 2019;296:54–67.
pubmed: 30658124 pmcid: 6379151
Tajdaran K, Shoichet MS, Gordon T, Borschel GH. A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506). Biotechnol Bioeng. 2015;112:1948–53.
pubmed: 25850693
Langert KA, Brey EM. Strategies for targeted delivery to the peripheral nerve. Front Neurosci. 2018;12:887.
pubmed: 30542262 pmcid: 6277764
Pfister LA, Papaloizos M, Merkle HP, Gander B. Nerve conduits and growth factor delivery in peripheral nerve repair. J Peripher Nerv Syst. 2007;12:65–82.
pubmed: 17565531
Wang Z, Han N, Wang J, Zheng H, Peng J, Kou Y, et al. Evaluation of biodegradable polymer conduits—poly (L-lactic acid)--for guiding sciatic nerve regeneration in mice. Methods. 2016;99:28–36.
Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Ann Rev Neurosci. 2001;24:1217–81.
pubmed: 11520933
Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012;10:239.
pubmed: 23190582 pmcid: 3543237
Evans GR, Brandt K, Katz S, Chauvin P, Otto L, Bogle M, et al. Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration. Biomaterials. 2002;23:841–8.
pubmed: 11774850
Frost HK, Andersson T, Johansson S, Englund-Johansson U, Ekström P, Dahlin LB, et al. Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo. Sci Rep. 2018;8:16716.
pubmed: 30425260 pmcid: 6233209
Fitzgerald R, Bass LM, Goldberg DJ, Graivier MH, Lorenc ZP. Physiochemical characteristics of poly-L-lactic acid (PLLA). Aesthet Surg J. 2018;38:S13–7.
pubmed: 29897517
Yilgör E, Yurtsever E, Yilgör I. Hydrogen bonding and polyurethane morphology. II. Spectroscopic, thermal and crystallization behavior of polyether blends with 1,3-dimethylurea and a model urethane compound. Polymer. 2002;43:6561–8.
Aparicio Gallego E, Castilla Peris C, Díez García MT, et al. Therapeutic behavior of a hydrocolloid dressing. Its evolution in the treatment of acute and chronic dermal ulcers. Rev. Enferm. 2005;28:49–55.
Simmons A, Padsalgikar AD, Ferris LM, Poole-Warren LA. Biostability and biological performance of a PDMS-based polyurethane for controlled drug release. Biomaterials. 2008;29:2987–95.
pubmed: 18436300
Malcolm RK, McCullagh SD, Woolfson AD, et al. Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial. J Control Rel. 2004;97:313–20.
Maeda H, Brandon M, Sano A. Design of controlled-release formulation for ivermectin using silicone. Int J Pharm. 2003;261:9–19.
pubmed: 12878391
Tallury P, Alimohammadi N, Kalachandra S. Poly(ethylene-co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: effect of drug combination, copolymer composition and coating on the drug release rate. Dent Mater. 2007;23:404–9.
pubmed: 16556460
de Queiroz AA, Abraham GA, Higa OZ. Controlled release of 5-fluorouridine from radiation-crosslinked poly(ethylene-co-vinyl acetate) films. Acta Biomater. 2006;2:641–50.
pubmed: 16876492
Labroo P, Ho S, Sant H, Shea J, Gale BK, Agarwal J. Controlled delivery of FK506 to improve nerve regeneration. Shock. 2016;46:154–9.
pubmed: 27058050
Labroo P, Shea J, Edwards K, Ho S, David B, Sant H, et al. Novel drug delivering conduit for peripheral nerve regeneration. J Neural Eng. 2017;14:066011.
pubmed: 28829045
Ho S, Labroo P, Lin KM, Sant H, Shea J, Gale BK, et al. Designing a novel drug delivering nerve guide: a preliminary study. J Med Biol Eng. 2019;39:294–304.
Labroo P, Hilgart D, Davis B, Lambert C, Sant H, Gale B, et al. Drug-delivering nerve conduit improves regeneration in a critical-sized gap. Biotechnol Bioeng. 2019;116:143–54.
pubmed: 30229866
Crank J. The mathematics of diffusion. 2nd ed. Oxford: Clarendon Press; 1975.
Grassi M, Grassi G. Mathematical modelling and controlled drug delivery: matrix systems. Curr Drug Deliv. 2005;2:97–116.
pubmed: 16305412
Siepmann J, Siepmann F. Modeling of diffusion controlled drug delivery. J Control Release. 2012;161:351–62.
pubmed: 22019555
Higuchi T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.
pubmed: 14088963
Ritger PL, Peppas NA. 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. J Control Release. 1987;5:23–36.
Peppas NA, Sahlin JJ. A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm. 1989;57:169–72.
Serra L, Domenech J, Peppas NA. Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels. Biomaterials. 2006;27:5440–51.
pubmed: 16828864
Brannon-Peppas L. Recent advances on the use of biodegradable microparticles and nanoparticles in controlled drug delivery. Int J Pharm. 1995;116:1–9.
Narasimhan B, Peppas NA. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier. J Pharm Sci. 1997;86:297–304.
pubmed: 9050796
Rothstein SN, Federspiel WJ, Little SR. A unified mathematical model for the prediction of controlled release from surface and bulk eroding polymer matrices. Biomaterial. 2009;30:1657–64.
Lao LL, Venkatraman SS, Peppas NA. Modeling of drug release from biodegradable polymer blends. Eur J Pharm Biopharm. 2008;70:796–803.
pubmed: 18577449
McGinty S, Pontrelli G. A general model of coupled drug release and tissue absorption for drug delivery devices. J Control Release. 2015;217:327–36.
pubmed: 26390809
Stroh M, Zipfel WR, Williams RM, Webb WW, Saltzman WM. Diffusion of nerve growth factor in rat striatum as determined by multiphoton microscopy. Biophys J. 2003;85:581–8.
pubmed: 12829512 pmcid: 1303113
Popov S, Poo MM. Diffusional transport of macromolecules in developing nerve processes. J Neurosci. 1992;12:77–85.
pubmed: 1370324 pmcid: 6575694
Sutter A, Riopelle RJ, Harris-Warrick RM, Shooter EM. Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. J Biol Chem. 1979;254:5972–82.
pubmed: 571871
Sutter A, Riopelle R, Harris-Warrick RM, Shooter EM. The heterogeneity of nerve growth factor receptors. Prog Clin Biol Res. 1979;31:659–67.
pubmed: 231780
Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus. 2004;16:E1.
pubmed: 15174821
Lin KM, Shea J, Gale B, Sant H, Larrabee P, Agarwal J. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth. J Micromech Microeng. 2016;26:045016.
Arrio-Dupont M, Cribier S, Foucault G, Devaux P, d’Albis A. Diffusion of fluorescently labeled macromolecules in cultures muscle cells. Biophys J. 1996;70:2327–32.
pubmed: 9172756 pmcid: 1225207

Auteurs

Pratima Labroo (P)

Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.

Scott Ho (S)

Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.

Himanshu Sant (H)

Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.

Jill E Shea (JE)

Department of Surgery, University of Utah, 30 N 1900 E, 3b400, Salt Lake City, UT, 84112-9057, USA.

Jayant Agarwal (J)

Department of Surgery, University of Utah, 30 N 1900 E, 3b400, Salt Lake City, UT, 84112-9057, USA. jay.agarwal@hsc.utah.edu.

Bruce Gale (B)

Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.

Articles similaires

Humans Pharmaceutical Preparations Drug Utilization Prescription Drugs
Humans Middle Aged Female Male Surveys and Questionnaires
Vancomycin Polyesters Anti-Bacterial Agents Models, Theoretical Drug Liberation

Classifications MeSH