Hollow Microparticles as a Superior Delivery System over Solid Microparticles for the Encapsulation of Peptides

• Published in: Pharmaceutical research Vol. 35; no. 10; pp. 185 - 10
• Main Authors: Kharel, Sharad, Gautam, Archana, Dickescheid, Andreas, Loo, Say Chye Joachim
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-10-2018; Springer; Springer Nature B.V
• Subjects: Analysis; Bioavailability; Biochemistry; Biodegradability; Biodegradation; Biological activity; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemical compounds; Encapsulation; Glucagon; Health aspects; Homeopathy; Materia medica and therapeutics; Medical Law; Microparticles; Molecular weight; Peptides; pH effects; Pharmacology/Toxicology; Pharmacy; Political aspects; Research Paper; Therapeutics; hollow; biodegradable; peptide; PLGA; bioactivity; acidic microenvironment
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-018-2461-y

Purpose
Peptides are gaining significant interests as therapeutic agents due to their high targeting specificity and potency. However, their low bioavailability and short half-lives limit their massive potential as therapeutics. The use of dense, solid particles of biodegradable polymer as a universal carrier for peptides also has its challenges, such as inefficient peptide release and low bioactivity. In this paper, it was established that hollow microparticles (h-MPs) instead of solid microparticles (s-MPs), as peptide carriers, could improve the release efficiency, while better preserving their bioactivity.
Methods
Glucagon like Peptide-1 (GLP-1) was encapsulated as a model peptide. Mass loss, average molecular weight changes, intraparticle pH, polymer-peptide interaction and release studies, together with bioactivity assessment of the peptide for s-MPs and h-MPs were systematically analyzed and evaluated for efficacy.
Results
The intraparticle pH of s-MPs was as low as 2.64 whereas the pH of h-MPs was 4.99 by day 7. Consequently, 93% of the peptide extracted from h-MPs was still bioactive while only 58% of the peptide extracted from s-MPs was bioactive. Likewise, the cumulative release of GLP-1 by day 14 from h-MPs showed a cumulative amount of 88 ± 8% as compared to 33 ± 6% for s-MPs.
Conclusions
The cumulative release of peptide can be significantly improved, and the bioactivity can be better preserved by simply using h-MPs instead of s-MPs as carriers.