Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Encapsulation and Controlled Release of the Therapeutic Neuropeptides Somatostatin and Oxytocin from the Lipidic Bicontinuous Cubic Phase

Jamie B. Strachan A , Durga Dharmadana A B , Brendan P. Dyett A , Céline Valéry B and Charlotte E. Conn https://orcid.org/0000-0002-3362-3453 A C
+ Author Affiliations
- Author Affiliations

A School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Vic. 3000, Australia.

B School of Health and Biomedical Sciences, Translational Immunology and Nanotechnology Research Program, College of Science, Engineering and Health, RMIT University, Melbourne, Vic. 3083, Australia.

C Corresponding author. Email: charlotte.conn@rmit.edu.au

Australian Journal of Chemistry 73(10) 1042-1050 https://doi.org/10.1071/CH19573
Submitted: 4 November 2019  Accepted: 17 April 2020   Published: 17 June 2020

Abstract

Therapeutic delivery of neuropeptides including oxytocin and somatostatin is associated with numerous difficulties including low stability, low oral bioavailability, and a short half-life in vivo. For delivery to the brain, these issues are exacerbated by difficulties in crossing the blood–brain barrier. Lipid-based nanomaterials may offer specific advantages for the delivery of therapeutic peptides including good biocompatibility, retention of peptide activity, and controlled release properties. Herein we have investigated the use of the lipid bicontinuous cubic phase as a depot formulation for the controlled release of the neuropeptides oxytocin and somatostatin. Retention of the cubic architecture was confirmed up to high peptide concentrations of at least 30 mg mL−1 for both peptides. Encapsulation had only minimal effect on the peptide secondary structure in both cases. Controlled release of the peptides from the cubic phase was diffusion controlled over the first 24 h. The time-dependent self-assembly of somatostatin into nanofibrils within the bicontinuous cubic phase led to a unique two-stage release mechanism, with diffusion-controlled release of the peptide monomer over the first 24 h followed by a much slower linear release of the peptide from the nanofibrils. Results suggest that the lipid bicontinuous cubic phase is a highly prospective nanomaterial for the encapsulation and controlled release of neuropeptide therapeutics.


References

[1]  U. Rai, T. R. Thrimawithana, C. Valery, S. A. Young, Pharmacol. Ther. 2015, 152, 98.
         | Crossref | GoogleScholarGoogle Scholar | 25956467PubMed |

[2]  B. O. Boehm, R. H. Lustig, Best Pract. Res. Clin. Gastroenterol. 2002, 16, 493.
         | Crossref | GoogleScholarGoogle Scholar | 12079271PubMed |

[3]  WHO Expert Committee on the Selection, Use of Essential Medicines, and World Health Organization, The Selection and Use of Essential Medicines: Report of the WHO Expert Committee 2013 (including the 18th WHO Model List of Essential Medicines and the 4th WHO Model List of Essential Medicines for Children), Vol. 985 2014 (World Health Organization: Geneva).

[4]  H. Acar, J. M. Ting, S. Srivastava, J. L. LaBelle, M. V. Tirrell, Chem. Soc. Rev. 2017, 46, 6553.
         | Crossref | GoogleScholarGoogle Scholar | 28902203PubMed |

[5]  J. Hutchinson, S. Burholt, I. Hamley, J. Pept. Sci. 2017, 23, 82.
         | Crossref | GoogleScholarGoogle Scholar | 28127868PubMed |

[6]  Y. Shechter, E. Heldman, K. Sasson, T. Bachar, M. Popov, M. Fridkin, ACS Chem. Neurosci. 2010, 1, 399.
         | Crossref | GoogleScholarGoogle Scholar | 22778833PubMed |

[7]  A. Hawe, R. Poole, S. Romeijn, P. Kasper, R. Van Der Heijden, W. Jiskoot, Pharm. Res. 2009, 26, 1679.
         | Crossref | GoogleScholarGoogle Scholar | 19343484PubMed |

[8]  D. Dharmadana, N. P. Reynolds, C. Dekiwadia, C. E. Conn, C. Valéry, Nanoscale 2018, 10, 18195.
         | Crossref | GoogleScholarGoogle Scholar | 30141801PubMed |

[9]  A. P. Higueruelo, H. Jubb, T. L. Blundell, Curr. Opin. Pharmacol. 2013, 13, 791.
         | Crossref | GoogleScholarGoogle Scholar | 23735579PubMed |

[10]  H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. Bhat, H. Weissig, I. Shindyalov, P. Bourne, Nucleic Acids Res. 2000, 28, 235.
         | Crossref | GoogleScholarGoogle Scholar | 10592235PubMed |

[11]  A. Anoop, S. Ranganathan, B. Das Dhaked, N. N. Jha, S. Pratihar, S. Ghosh, S. Sahay, S. Kumar, S. Das, M. Kombrabail, K. Agarwal, R. S. Jacob, P. Singru, P. Bhaumik, R. Padinhateeri, A. Kumar, S. K. Maji, J. Biol. Chem. 2014, 289, 16884.
         | Crossref | GoogleScholarGoogle Scholar | 24782311PubMed |

[12]  J. Koehbach, M. O’Brien, M. Muttenthaler, M. Miazzo, M. Akcan, A. G. Elliott, N. L. Daly, P. J. Harvey, S. Arrowsmith, S. Gunasekera, T. J. Smith, S. Wray, U. Göransson, P. E. Dawson, D. J. Craik, M. Freissmuth, C. W. Gruber, Proc. Natl. Acad. Sci. USA 2013, 110, 21183.
         | Crossref | GoogleScholarGoogle Scholar | 24248349PubMed |

[13]  V. D. Tsu, Lancet 2004, 363, 75.
         | Crossref | GoogleScholarGoogle Scholar | 14724005PubMed |

[14]  F. Althabe, A. Mazzoni, M. L. Cafferata, L. Gibbons, A. Karolinski, D. Armbruster, P. Buekens, J. M. Belizán, Int. J. Gynaecol. Obstet. 2011, 114, 184.
         | Crossref | GoogleScholarGoogle Scholar | 21693378PubMed |

[15]  V. Tsu, A. Sutanto, K. Vaidya, P. Coffey, A. Widjaya, Int. J. Gynaecol. Obstet. 2003, 83, 103.
         | Crossref | GoogleScholarGoogle Scholar | 14511884PubMed |

[16]  V. D. Tsu, H. T. Luu, T. T. Mai, Midwifery 2009, 25, 461.
         | Crossref | GoogleScholarGoogle Scholar | 18281131PubMed |

[17]  R. J. Prankerd, T.-H. Nguyen, J. P. Ibrahim, R. J. Bischof, G. C. Nassta, L. D. Olerile, A. S. Russell, F. Meiser, H. C. Parkington, H. A. Coleman, PLoS One 2013, 8, e82965.
         | Crossref | GoogleScholarGoogle Scholar | 24376618PubMed |

[18]  M. Bronstein, N. Musolino, R. Jallad, J. M. Cendros, J. Ramis, R. Obach, A. Leselbaum, F. Catus, Clin. Endocrinol. 2005, 63, 514.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  U. Rai, T. R. Thrimawithana, D. Dharmadana, C. Valery, S. A. Young, Pept. Sci. 2018, 110, e23085.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  S. Mitragotri, P. A. Burke, R. Langer, Nat. Rev. Drug Discov. 2014, 13, 655.
         | Crossref | GoogleScholarGoogle Scholar | 25103255PubMed |

[21]  M. Kanapathipillai, A. Brock, D. E. Ingber, Adv. Drug Deliv. Rev. 2014, 79–80, 107.
         | Crossref | GoogleScholarGoogle Scholar | 24819216PubMed |

[22]  H. D. Lagassé, A. Alexaki, V. L. Simhadri, N. H. Katagiri, W. Jankowski, Z. E. Sauna, C. Kimchi-Sarfaty, F1000 Res. 2017, 6, 113.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  M. Riley, W. Vermerris, Nanomaterials 2017, 7, 94.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  S. Ahmad, A. A. Zamry, H.-T. T. Tan, K. K. Wong, J. Lim, R. Mohamud, Mol. Immunol. 2017, 91, 123.
         | Crossref | GoogleScholarGoogle Scholar | 28898717PubMed |

[25]  H.-W. Sung, M.-C. Chen, Y.-H. Lin, H.-F. Liang, H. Tu, Nanoparticles for Protein Drug Delivery. Google Patents: 2009.

[26]  K. Chaturvedi, K. Ganguly, M. N. Nadagouda, T. M. Aminabhavi, J. Control. Release 2013, 165, 129.
         | Crossref | GoogleScholarGoogle Scholar | 23159827PubMed |

[27]  P. Fonte, F. Araújo, C. Silva, C. Pereira, S. Reis, H. A. Santos, B. Sarmento, Biotechnol. Adv. 2015, 33, 1342.
         | Crossref | GoogleScholarGoogle Scholar | 25728065PubMed |

[28]  P. Mukhopadhyay, S. Chakraborty, S. Bhattacharya, R. Mishra, P. P. Kundu, Int. J. Biol. Macromol. 2015, 72, 640.
         | Crossref | GoogleScholarGoogle Scholar | 25239194PubMed |

[29]  S. Behzadi, V. Serpooshan, W. Tao, M. A. Hamaly, M. Y. Alkawareek, E. C. Dreaden, D. Brown, A. M. Alkilany, O. C. Farokhzad, M. Mahmoudi, Chem. Soc. Rev. 2017, 46, 4218.
         | Crossref | GoogleScholarGoogle Scholar | 28585944PubMed |

[30]  D. Bobo, K. J. Robinson, J. Islam, K. J. Thurecht, S. R. Corrie, Pharm. Res. 2016, 33, 2373.
         | Crossref | GoogleScholarGoogle Scholar | 27299311PubMed |

[31]  A. Nemmar, J. A. Holme, I. Rosas, P. E. Schwarze, E. Alfaro-Moreno, Biomed. Res. Int. 2013, 2013, 279371.
         | Crossref | GoogleScholarGoogle Scholar | 23936830PubMed |

[32]  S. V. Talluri, G. Kuppusamy, V. V. S. R. Karri, S. Tummala, S. V. Madhunapantula, Drug Deliv. 2016, 23, 1291.
         | Crossref | GoogleScholarGoogle Scholar | 26430913PubMed |

[33]  C. E. Conn, C. J. Drummond, Soft Matter 2013, 9, 3449.
         | Crossref | GoogleScholarGoogle Scholar |

[34]  T. G. Meikle, C. E. Conn, F. Separovic, C. J. Drummond, RSC Adv. 2016, 6, 68685.
         | Crossref | GoogleScholarGoogle Scholar |

[35]  C. Darmanin, S. Sarkar, L. Castelli, C. E. Conn, Cryst. Growth Des. 2016, 16, 5014.
         | Crossref | GoogleScholarGoogle Scholar |

[36]  E. Nazaruk, A. Majkowska-Pilip, R. Bilewicz, ChemPlusChem 2017, 82, 570.
         | Crossref | GoogleScholarGoogle Scholar | 31961592PubMed |

[37]  N. Matougui, L. Boge, A.-C. Groo, A. Umerska, L. Ringstad, H. Bysell, P. Saulnier, Int. J. Pharm. 2016, 502, 80.
         | Crossref | GoogleScholarGoogle Scholar | 26899976PubMed |

[38]  L. van ‘t Hag, X. Li, T. G. Meikle, S. V. Hoffmann, N. C. Jones, J. S. Pedersen, A. M. Hawley, S. L. Gras, C. E. Conn, C. J. Drummond, Langmuir 2016, 32, 6882.
         | Crossref | GoogleScholarGoogle Scholar | 27315326PubMed |

[39]  B. Erdlenbruch, C. Schinkhof, W. Kugler, D. E. Heinemann, J. Herms, H. Eibl, M. Lakomek, Br. J. Pharmacol. 2003, 139, 685.
         | Crossref | GoogleScholarGoogle Scholar | 12812991PubMed |

[40]  B. Erdlenbruch, V. Jendrossek, W. Kugler, H. Eibl, M. Lakomek, Cancer Chemother. Pharmacol. 2002, 50, 299.
         | Crossref | GoogleScholarGoogle Scholar | 12357304PubMed |

[41]  B. P. Dyett, H. Yu, J. Strachan, C. J. Drummond, C. E. Conn, Nat. Commun. 2019, 10, 4492.
         | Crossref | GoogleScholarGoogle Scholar | 31582802PubMed |

[42]  J. M. Seddon, A. M. Squires, C. E. Conn, O. Ces, A. J. Heron, X. Mulet, G. C. Shearman, R. H. Templer, Philos. Trans. R. Soc. A 1847, 2006, 2635.

[43]  A. Hawe, W. L. Hulse, W. Jiskoot, R. T. Forbes, Pharm. Res. 2011, 28, 2302.
         | Crossref | GoogleScholarGoogle Scholar | 21560019PubMed |

[44]  A. Angelova, M. Ollivon, A. Campitelli, C. Bourgaux, Langmuir 2003, 19, 6928.
         | Crossref | GoogleScholarGoogle Scholar |

[45]  D. Dharmadana, N. P. Reynolds, C. Dekiwadia, C. E. Conn, C. Valery, Nanoscale 2018, 10, 18195.
         | Crossref | GoogleScholarGoogle Scholar | 30141801PubMed |

[46]  R. Malishev, R. Abbasi, R. Jelinek, L. Chai, Biochemistry 2018, 57, 5230.
         | Crossref | GoogleScholarGoogle Scholar | 29565118PubMed |

[47]  P. L. Ritger, N. A. Peppas, J. Control. Release 1987, 5, 37.
         | Crossref | GoogleScholarGoogle Scholar |

[48]  Y. Fu, W. J. Kao, Expert Opin. Drug Deliv. 2010, 7, 429.
         | Crossref | GoogleScholarGoogle Scholar | 20331353PubMed |

[49]  T. G. Meikle, S. Yao, A. Zabara, C. E. Conn, C. J. Drummond, F. Separovic, Nanoscale 2017, 9, 2471.
         | Crossref | GoogleScholarGoogle Scholar | 28045170PubMed |