Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 18;27(1):1667-1675.
doi: 10.1080/10717544.2020.1850919.

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics

Junqiu Zhai  1 , Zhanlun Ou  1 , Liuting Zhong  1 , Yu-E Wang  1 , Li-Ping Cao  2 , Shixia Guan  1
Affiliations

Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics

Junqiu Zhai et al. Drug Deliv. .

Abstract

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.

Keywords: Exenatide; inside-porous microspheres; long-acting; release behavior; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Scheme 1.
Scheme 1.
Schematic of the synthetic process for the EXT-loaded inside-porous PLGA microspheres.
Figure 1.
Figure 1.
(A) Encapsulation efficiency and drug-loading capacity of EXT-PMS prepared by using different PLGA (50/50) concentrations. (B) Cumulative release of EXT from EXT-PMS prepared by using different PLGA (50/50) concentration (mg/mL). (C) Drug-loading capacity and encapsulation efficiency of EXT-PMS prepared by using different mass ratio of EXT to PLGA. (D) Cumulative release of EXT from EXT-PMS prepared by using different mass ratio of EXT to PLGA. (E) Drug-loading capacity and encapsulation efficiency of EXT-PMS prepared by using different volume ratio of oil to W1 phase. (F) Cumulative release of EXT from EXT-PMS prepared by using different volume ratio of oil to W1 phase.
Figure 2.
Figure 2.
(A) Drug-loading capacity and encapsulation efficiency of EXT-PMS prepared by using different proportion of NH4HCO3 (%). (B) Cumulative release of EXT from EXT-PMS prepared by using different proportion of NH4HCO3 (%).
Figure 3.
Figure 3.
(A) DSC thermograms of EXT-PMS, PLGA (50/50) and EXT. (B) CLSM images of F-EXT-PMS. (C) SEM images of surface of EXT-PMS. (D) SEM images of internal structure of EXT-PMS.
Figure 4.
Figure 4.
Plasma concentration–time curves of EXT-MS or EXT-PMS following subcutaneous administration in SD rats.
See this image and copyright information in PMC

References

    1. Bae SE, Son JS, Park K, Han DK. (2009). Fabrication of covered porous PLGA microspheres using hydrogen peroxide for controlled drug delivery and regenerative medicine. J Control Release 133:37–43. - PubMed
    1. Cai Y, Wei L, Ma L, et al. (2013). Long-acting preparations of exenatide. Drug Des Devel Ther 7:963–70. - PMC - PubMed
    1. Chatterjee S, Khunti K, Davies MJ. (2017). Type 2 diabetes. The Lancet 389:2239–51. - PubMed
    1. Danhier F, Ansorena E, Silva JM, et al. (2012). PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–22. - PubMed
    1. Davidson MB, Bate G, Kirkpatrick P. (2005). Exenatide. Nat Rev Drug Discov 4:713–4. - PubMed

MeSH terms