Perspective

Understanding the burst release phenomenon: toward designing effective nanoparticulate drug-delivery systems

Sourav Bhattacharjee

Sourav Bhattacharjee

*Author for correspondence: Tel.: +353 1 716 6271;

E-mail Address: sourav.bhattacharjee@ucd.ie

https://orcid.org/0000-0002-6528-6877

School of Veterinary Medicine, University College Dublin (UCD), Belfield, Dublin 4, Ireland

Search for more papers by this author

Published Online:23 Dec 2020https://doi.org/10.4155/tde-2020-0099

View article

Abstract

Burst release of encapsulated drug with release of a significant fraction of payload into release medium within a short period, both in vitro and in vivo, remains a challenge for translation. Such unpredictable and uncontrolled release is often undesirable, especially from the perspective of developing sustained-release formulations. Moreover, a brisk release of the payload upsets optimal release kinetics. This account strives toward understanding burst release noticed in nanocarriers and investigates its causes. Various mathematical models to explain such untimely release were also examined, including their strengths and weaknesses. Finally, the account revisits current techniques of limiting burst release from nanocarriers and prioritizes future directions that harbor potential of fruitful translation by reducing such occurrences.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Hua S, De Matos MBC, Metselaar JM, Storm G. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: pathways for translational development and commercialization. Front. Pharmacol. 9, 790 (2018).
MedlineGoogle Scholar
2. Zhao N, Woodle MC, Mixson AJ. Advances in delivery systems for doxorubicin. J. Nanomed. Nanotechnol. 9(5), 519 (2018).
MedlineGoogle Scholar
3. Lee H, Park S, Kang JE, Lee HM, Kim SA, Rhie SJ. Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: a meta-analysis. Sci. Rep. 10(1), 530 (2020).
Medline CASGoogle Scholar
4. Li J, Mooney DJ. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 1(12), 16071 (2016). • Comprehensive review on hydrogel materials for drug delivery.
Medline CASGoogle Scholar
5. Lynch CR, Kondiah PPD, Choonara YE, Du Toit LC, Ally N, Pillay V. Hydrogel biomaterials for application in ocular drug delivery. Front. Bioeng. Biotechnol. 8, 228 (2020).
MedlineGoogle Scholar
6. Gangrade A, Mandal BB. Injectable carbon nanotube impregnated silk based multifunctional hydrogel for localized targeted and on-demand anticancer drug delivery. ACS Biomater. Sci. Eng. 5(5), 2365–2381 (2019).
Medline CASGoogle Scholar
7. Subbiah R, Guldberg RE. Materials science and design principles of growth factor delivery systems in tissue engineering and regenerative medicine. Adv. Healthc. Mater. 8(1), 1801000 (2019).
Google Scholar
8. Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun. 9(1), 1410 (2018).
MedlineGoogle Scholar
9. Hristov D, McCartney F, Beirne J et al. Silica-coated nanoparticles with a core of zinc, L-arginine, and a peptide designed for oral delivery. ACS Appl. Mater. Interfaces 12(1), 1257–1269 (2020). • A study on the synthesis and characterization of silica nanoparticles with encapsulated insulin.
Medline CASGoogle Scholar
10. Mourdikoudis S, Pallares RM, Thanh NTK. Characterization techniques for nanoparticles: comparison and complementarity upon studying nanoparticle properties. Nanoscale 10(27), 12871–12934 (2018).
Medline CASGoogle Scholar
11. Rodrigues De Azevedo C, Von Stosch M, Costa MS et al. Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics. Int. J. Pharm. 532(1), 229–240 (2017). •• An interesting study on the use of machine learning while analyzing data on drug release.
MedlineGoogle Scholar
12. Karimi M, Bahrami S, Ravari SB et al. Albumin nanostructures as advanced drug delivery systems. Exp. Opin. Drug Deliv. 13(11), 1609–1623 (2016).
Medline CASGoogle Scholar
13. Niwa T, Takeuchi H, Hino T, Kunou N, Kawashima Y. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D,L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. J. Control. Rel. 25(1), 89–98 (1993).
CASGoogle Scholar
14. Li S-D, Huang L. Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J. Control. Rel. 145(3), 178–181 (2010).
Medline CASGoogle Scholar
15. Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Control. Rel. 73(2), 121–136 (2001). •• Crucial review on burst release.
Medline CASGoogle Scholar
16. Moradi Kashkooli F, Soltani M, Souri M. Controlled anti-cancer drug release through advanced nano-drug delivery systems: static and dynamic targeting strategies. J. Control. Rel. 327, 316–349 (2020). •• Explains the various drug release models from nanocarriers in detail.
MedlineGoogle Scholar
17. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric systems for controlled drug release. Chem. Rev. 99(11), 3181–3198 (1999).
Medline CASGoogle Scholar
18. Arifin DY, Lee LY, Wang C-H. Mathematical modeling and simulation of drug release from microspheres: implications to drug delivery systems. Adv. Drug Deliv. Rev. 58(12), 1274–1325 (2006).
Medline CASGoogle Scholar
19. Lowinger MB, Barrett SE, Zhang F, Williams RO. Sustained release drug delivery applications of polyurethanes. Pharmaceutics 10(2), 55 (2018).
Google Scholar
20. Wu F, Jin T. Polymer-based sustained-release dosage forms for protein drugs, challenges, and recent advances. AAPS Pharm. Sci. Tech. 9(4), 1218–1229 (2008).
Medline CASGoogle Scholar
21. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA. Polymers for drug delivery systems. Annu. Rev. Chem. Biomol. Eng. 1, 149–173 (2010).
Medline CASGoogle Scholar
22. Patel RB, Carlson AN, Solorio L, Exner AA. Characterization of formulation parameters affecting low molecular weight drug release from in situ forming drug delivery systems. J. Biomed. Mater. Res. A 94(2), 476–484 (2010).
MedlineGoogle Scholar
23. Mu L, Feng S-S. PLGA/TPGS Nanoparticles for controlled release of paclitaxel: effects of the emulsifier and drug loading ratio. Pharm. Res. 20(11), 1864–1872 (2003).
Medline CASGoogle Scholar
24. Sah H, Toddywala R, Chien YW. The influence of biodegradable microcapsule formulations on the controlled release of a protein. J. Control. Rel. 30(3), 201–211 (1994).
CASGoogle Scholar
25. Jeyanthi R, Mehta RC, Thanoo BC, Deluca PP. Effect of processing parameters on the properties of peptide-containing PLGA microspheres. J. Microencapsul. 14(2), 163–174 (1997).
Medline CASGoogle Scholar
26. Mao S, Shi Y, Li L, Xu J, Schaper A, Kissel T. Effects of process and formulation parameters on characteristics and internal morphology of poly(D,L-lactide-co-glycolide) microspheres formed by the solvent evaporation method. Eur. J. Pharm. Biopharm. 68(2), 214–223 (2008). • Investigates the effects of various synthetic conditions on burst release.
Medline CASGoogle Scholar
27. Penco M, Marcioni S, Ferruti P, D'antone S, Deghenghi R. Degradation behaviour of block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments. Biomaterials 17(16), 1583–1590 (1996).
Medline CASGoogle Scholar
28. Brazel CS, Peppas NA. Mechanisms of solute and drug transport in relaxing, swellable, hydrophilic glassy polymers. Polymer 40(12), 3383–3398 (1999). • Important paper on the release kinetics of drug from polymeric hydrogel matrices.
CASGoogle Scholar
29. Shively ML, Coonts BA, Renner WD, Southard JL, Bennett AT. Physico-chemical characterization of a polymeric injectable implant delivery system. J. Control. Rel. 33(2), 237–243 (1995).
CASGoogle Scholar
30. Jalil R, Nixon JR. Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties. J. Microencapsul. 7(3), 297–325 (1990).
Medline CASGoogle Scholar
31. Patil NS, Dordick JS, Rethwisch DG. Macroporous poly(sucrose acrylate) hydrogel for controlled release of macromolecules. Biomaterials 17(24), 2343–2350 (1996). • An interesting paper explaining the influence of monomer concentration on hydrogel properties.
Medline CASGoogle Scholar
32. Tzafriri AR. Mathematical modeling of diffusion-mediated release from bulk degrading matrices. J. Control. Rel. 63(1), 69–79 (2000).
Medline CASGoogle Scholar
33. Peppas NA, Narasimhan B. Mathematical models in drug delivery: how modeling has shaped the way we design new drug delivery systems. J. Control. Rel. 190, 75–81 (2014). •• An excellent paper on the various mathematical models to fit drug release data.
Medline CASGoogle Scholar
34. Mircioiu C, Voicu V, Anuta V et al. Mathematical modeling of release kinetics from supramolecular drug delivery systems. Pharmaceutics 11(3), 140 (2019).
Medline CASGoogle Scholar
35. Huang J, Wigent RJ, Schwartz JB. Nifedipine molecular dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blends for controlled drug delivery: effect of matrix composition. Drug Dev. Ind. Pharm. 32(10), 1185–1197 (2006).
Medline CASGoogle Scholar
36. Pourtalebi Jahromi L, Ghazali M, Ashrafi H, Azadi A. A comparison of models for the analysis of the kinetics of drug release from PLGA-based nanoparticles. Heliyon 6(2), e03451 (2020).
MedlineGoogle Scholar
37. Paolino D, Tudose A, Celia C, Di Marzio L, Cilurzo F, Mircioiu C. Mathematical models as tools to predict the release kinetic of fluorescein from lyotropic colloidal liquid crystals. Materials 12(5), 693 (2019).
CASGoogle Scholar
38. Zou H, Banerjee P, Leung SSY, Yan X. Application of pharmacokinetic-pharmacodynamic modeling in drug delivery: development and challenges. Front. Pharmacol. 11, 997 (2020).
Medline CASGoogle Scholar
39. Huang W, Lee SL, Yu LX. Mechanistic approaches to predicting oral drug absorption. AAPS J. 11(2), 217–224 (2009).
Medline CASGoogle Scholar
40. Chetty M, Johnson TN, Polak S, Salem F, Doki K, Rostami-Hodjegan A. Physiologically based pharmacokinetic modelling to guide drug delivery in older people. Adv. Drug Deliv. Rev. 135, 85–96 (2018).
Medline CASGoogle Scholar
41. Grassi M, Lamberti G, Cascone S, Grassi G. Mathematical modeling of simultaneous drug release and in vivo absorption. Int. J. Pharm. 418(1), 130–141 (2011).
Medline CASGoogle Scholar
42. Kim H, Fassihi R. Application of binary polymer system in drug release rate modulation. 2. Influence of formulation variables and hydrodynamic conditions on release kinetics. J. Pharm. Sci. 86(3), 323–328 (1997).
MedlineGoogle Scholar
43. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm. Acta. Helv. 60(4), 110–111 (1985). • Provides important insights into the release kinetics of drug molecules from matrices.
Medline CASGoogle Scholar
44. Peppas NA, Sahlin JJ. A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int. J. Pharm. 57(2), 169–172 (1989).
CASGoogle Scholar
45. Klech CM, Simonelli AP. Examination of the moving boundaries associated with non-fickian water swelling of glassy gelatin beads: effect of solution pH. J. Membr. Sci. 43(1), 87–101 (1989).
CASGoogle Scholar
46. Batycky RP, Hanes J, Langer R, Edwards DA. A theoretical model of erosion and macromolecular drug release from biodegrading microspheres. J. Pharm. Sci. 86(12), 1464–1477 (1997).
Medline CASGoogle Scholar
47. Rhine WD. Sukhatme V. Hsieh DST. Langer RS. A new approach to achieve zero-order release kinetics from diffusion-controlled polymer matrix systems. In: Controlled Release of Biologically Active Agents. Baker R (Ed.). Wiley, NY, USA (1987).
Google Scholar
48. Heller J, Baker RW. Theory and practice of controlled drug delivery from bioerodible polymers. In: Controlled Release of Bioactive Materials Baker RW (Ed.). Academic Press, NY, USA, 1–17 (1980).
Google Scholar
49. Corrigan OI, Li X. Quantifying drug release from PLGA nanoparticulates. Eur. J. Pharm. Sci. 37(3), 477–485 (2009). •• Describes an interesting mathematical model for burst release.
Medline CASGoogle Scholar
50. Lucero-Acuña A, Guzmán R. Nanoparticle encapsulation and controlled release of a hydrophobic kinase inhibitor: three stage mathematical modeling and parametric analysis. Int. J. Pharm. 494(1), 249–257 (2015).
Medline CASGoogle Scholar
51. Hussain Z, Arooj M, Malik A et al. Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy. Artif. Cells Nanomed. Biotechnol. 46(Suppl. 2), 1015–1024 (2018).
Medline CASGoogle Scholar
52. Andresen TL, Thompson DH, Kaasgaard T. Enzyme-triggered nanomedicine: drug release strategies in cancer therapy. Mol. Membr. Biol. 27(7), 353–363 (2010).
Medline CASGoogle Scholar
53. Gao X, Cao Y, Song X et al. pH- and thermo-responsive poly(N-isopropylacrylamide-co-acrylic acid derivative) copolymers and hydrogels with LCST dependent on pH and alkyl side groups. J. Mater. Chem. B 1(41), 5578–5587 (2013).
Medline CASGoogle Scholar
54. Price PM, Mahmoud WE, Al-Ghamdi AA, Bronstein LM. Magnetic drug delivery: where the field is going. Front. Chem. 6, 619 (2018).
Medline CASGoogle Scholar
55. Mena-Giraldo P, Pérez-Buitrago S, Londoño-Berrío M, Ortiz-Trujillo IC, Hoyos-Palacio LM, Orozco J. Photosensitive nanocarriers for specific delivery of cargo into cells. Sci. Rep. 10(1), 2110 (2020).
Medline CASGoogle Scholar
56. Sánchez-Moreno P, De Vicente J, Nardecchia S, Marchal JA, Boulaiz H. Thermo-sensitive nanomaterials: recent advance in synthesis and biomedical applications. Nanomaterials 8(11), 935 (2018).
Google Scholar
57. Tharkar P, Varanasi R, Wong WSF, Jin CT, Chrzanowski W. Nano-enhanced drug delivery and therapeutic ultrasound for cancer treatment and beyond. Front. Bioeng. Biotechnol. 7, 324 (2019).
MedlineGoogle Scholar
58. Karimi M, Ghasemi A, Sahandi Zangabad P et al. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem. Soc. Rev. 45(5), 1457–1501 (2016).
Medline CASGoogle Scholar
59. Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J. Natl Cancer Inst. 98(5), 335–344 (2006).
Medline CASGoogle Scholar
60. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2(12), 751–760 (2007). •• An excellent review on the evolution of cancer nanomedicine with implications and challenges.
Medline CASGoogle Scholar
61. Ye M, Kim S, Park K. Issues in long-term protein delivery using biodegradable microparticles. J. Control. Rel. 146(2), 241–260 (2010).
Medline CASGoogle Scholar
62. Kim S, Shi Y, Kim JY, Park K, Cheng J-X. Overcoming the barriers in micellar drug delivery: loading efficiency, in vivo stability, and micelle–cell interaction. Exp. Opin. Drug Deliv. 7(1), 49–62 (2010).
Medline CASGoogle Scholar
63. Jette KK, Law D, Schmitt EA, Kwon GS. Preparation and drug loading of poly(ethylene glycol)-block-poly(ε-caprolactone) micelles through the evaporation of a cosolvent azeotrope. Pharm. Res. 21(7), 1184–1191 (2004).
Medline CASGoogle Scholar
64. Mahmud A, Xiong X-B, Lavasanifar A. Novel self-associating poly(ethylene oxide)-block-poly(ε-caprolactone) block copolymers with functional side groups on the polyester block for drug delivery. Macromolecules 39(26), 9419–9428 (2006).
CASGoogle Scholar
65. Mallapragada SK, Peppas NA, Colombo P. Crystal dissolution-controlled release systems. II. Metronidazole release from semicrystalline poly(vinyl alcohol) systems. J. Biomed. Mater. Res. 36(1), 125–130 (1997).
Medline CASGoogle Scholar
66. Devi KP, Rao KVR, Baveja S, Fathi M, Roth M. Zero-order release formulation of oxprenolol hydrochloride with swelling and erosion control. Pharm. Res. 6(4), 313–317 (1989).
Medline CASGoogle Scholar
67. Yang Y-Y, Chia H-H, Chung T-S. Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. J. Control. Rel. 69(1), 81–96 (2000). • An interesting study on the effect of temperature on the poly(lactic-co-glycolic acid) microspheres and drug release.
Medline CASGoogle Scholar
68. Ahmed AR, Elkharraz K, Irfan M, Bodmeier R. Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer. Pharm. Dev. Technol. 17(1), 66–72 (2012).
Medline CASGoogle Scholar
69. Shen Y, Zhan Y, Tang J et al. Multifunctioning pH-responsive nanoparticles from hierarchical self-assembly of polymer brush for cancer drug delivery. AIChE J. 54(11), 2979–2989 (2008).
CASGoogle Scholar
70. Tyrrell ZL, Shen Y, Radosz M. Near-critical fluid micellization for high and efficient drug loading: encapsulation of paclitaxel into PEG-b-PCL micelles. J. Phys. Chem. C 115(24), 11951–11956 (2011).
CASGoogle Scholar
71. Tyrrell ZL, Shen Y, Radosz M. Multilayered nanoparticles for controlled release of paclitaxel formed by near-critical micellization of triblock copolymers. Macromolecules 45(11), 4809–4817 (2012).
CASGoogle Scholar
72. Iijima M, Nagasaki Y, Okada T, Kato M, Kataoka K. Core-polymerized reactive micelles from heterotelechelic amphiphilic block copolymers. Macromolecules 32(4), 1140–1146 (1999).
CASGoogle Scholar
73. Meng F, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials 30(12), 2180–2198 (2009).
Medline CASGoogle Scholar
74. Xiong J, Meng F, Wang C, Cheng R, Liu Z, Zhong Z. Folate-conjugated crosslinked biodegradable micelles for receptor-mediated delivery of paclitaxel. J. Mater. Chem. 21(15), 5786–5794 (2011).
CASGoogle Scholar
75. Abdullah Al N, Lee H, Lee YS, Lee KD, Park SY. Development of disulfide core-crosslinked pluronic nanoparticles as an effective anticancer-drug-delivery system. Macromol. Biosci. 11(9), 1264–1271 (2011).
MedlineGoogle Scholar
76. Xiong X-B, Falamarzian A, Garg SM, Lavasanifar A. Engineering of amphiphilic block copolymers for polymeric micellar drug and gene delivery. J. Control. Rel. 155(2), 248–261 (2011).
Medline CASGoogle Scholar
77. Yokoyama M, Kwon GS, Okano T, Sakurai Y, Seto T, Kataoka K. Preparation of micelle-forming polymer-drug conjugates. Bioconjugate Chem. 3(4), 295–301 (1992).
Medline CASGoogle Scholar
78. Bae Y, Alani AWG, Rockich NC, Lai TSZC, Kwon GS. Mixed pH-sensitive polymeric micelles for combination drug delivery. Pharm. Res. 27(11), 2421–2432 (2010).
Medline CASGoogle Scholar
79. Aryal S, Hu C-MJ, Zhang L. Polymer-cisplatin conjugate nanoparticles for acid-responsive drug delivery. ACS Nano 4(1), 251–258 (2010). •• An interesting study on designing of an internal stimuli-responsive nanoformulation.
Medline CASGoogle Scholar
80. Wong L, Kavallaris M, Bulmus V. Doxorubicin conjugated, crosslinked, PEGylated particles prepared via one-pot thiol-ene modification of a homopolymer scaffold: synthesis and in vitro evaluation. Polym. Chem. 2(2), 385–393 (2011).
CASGoogle Scholar
81. Jarvis M, Krishnan V, Mitragotri S. Nanocrystals: a perspective on translational research and clinical studies. Bioeng. Transl. Med. 4(1), 5–16 (2018). • Explains the nanocrystal technology and how it addresses the solubility issue in drug delivery.
MedlineGoogle Scholar
82. Güncüm E, Işıklan N, Anlaş C, Ünal N, Bulut E, Bakırel T. Development and characterization of polymeric-based nanoparticles for sustained release of amoxicillin – an antimicrobial drug. Artif. Cells Nanomed. Biotechnol. 46(Suppl. 2), 964–973 (2018).
MedlineGoogle Scholar
83. Greish K, Mathur A, Bakhiet M, Taurin S. Nanomedicine: is it lost in translation? Ther. Deliv. 9(4), 269–285 (2018).
CASGoogle Scholar
84. Salvioni L, Rizzuto MA, Bertolini JA, Pandolfi L, Colombo M, Prosperi D. Thirty years of cancer nanomedicine: success, frustration, and hope. Cancers 11, 12 (2019).
Google Scholar
85. Sarmento B. Have nanomedicines progressed as much as we'd hoped for in drug discovery and development? Exp. Opin. Drug Discov. 14(8), 723–725 (2019).
MedlineGoogle Scholar
86. He H, Liu L, Morin EE, Liu M, Schwendeman A. Survey of clinical translation of cancer nanomedicines—lessons learned from successes and failures. Acc. Chem. Res. 52(9), 2445–2461 (2019).
Medline CASGoogle Scholar
87. Rangel-Yagui CO, Pessoa A Jr, Tavares LC. Micellar solubilization of drugs. J. Pharm. Pharm. Sci. 8(2), 147–165 (2005).
Medline CASGoogle Scholar
88. Mülhopt S, Diabaté S, Dilger M et al. Characterization of nanoparticle batch-to-batch variability. Nanomaterials 8(5), 311 (2018).
Google Scholar
89. Colombo P, Conte U, Gazzaniga A et al. Drug release modulation by physical restrictions of matrix swelling. Int. J. Pharm. 63(1), 43–48 (1990). • Interesting article on release of drug from swellable matrices.
CASGoogle Scholar
90. Colombo P. Swelling-controlled release in hydrogel matrices for oral route. Adv. Drug Deliv. Rev. 11(1), 37–57 (1993).
CASGoogle Scholar
91. Wheatley MA, Chang M, Park E, Langer R. Coated alginate microspheres: factors influencing the controlled delivery of macromolecules. J. Appl. Polym. Sci. 43(11), 2123–2135 (1991).
CASGoogle Scholar
92. Colombo P, Catellani PL, Peppas NA, Maggi L, Conte U. Swelling characteristics of hydrophilic matrices for controlled release: new dimensionless number to describe the swelling and release behavior. Int. J. Pharm. 88(1), 99–109 (1992).
CASGoogle Scholar
93. Lee PI. Effect of non-uniform initial drug concentration distribution on the kinetics of drug release from glassy hydrogel matrices. Polymer 25(7), 973–978 (1984).
CASGoogle Scholar
94. Savić R, Azzam T, Eisenberg A, Maysinger D. Assessment of the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles under biological conditions: a fluorogenic-based approach. Langmuir 22(8), 3570–3578 (2006).
Medline CASGoogle Scholar
95. Chen H, Kim S, He W et al. Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo Förster resonance energy transfer imaging. Langmuir 24(10), 5213–5217 (2008).
Medline CASGoogle Scholar
96. Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int. J. Pharm. 418(1), 6–12 (2011). •• Explains how the Higuchi equation can be misinterpreted and abused.
Medline CASGoogle Scholar
97. Siepmann J, Faisant N, Benoit J-P. A new mathematical model quantifying drug release from bioerodible microparticles using Monte Carlo simulations. Pharm. Res. 19(12), 1885–1893 (2002).
Medline CASGoogle Scholar

Vol. 12, No. 1

Metrics

Downloaded 821 times

History

Received 14 August 2020

Accepted 9 December 2020

Published online 23 December 2020

Published in print January 2021

Information

Keywords

Acknowledgments

The author would like to thank Prof. Dermot Brougham from UCD School of Chemistry for stimulating discussions.

Financial & competing interests disclosure

The study was funded by UCD Research. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download