Optimisation of a Microfluidic Method for the Delivery of a Small Peptide

Han, Felicity Y.1,2; Xu, Weizhi1,2; Kumar, Vinod1; Cui, Cedric S.1; Li, Xaria1; Jiang, Xingyu3,4; Woodruff, Trent M.1; Whittaker, Andrew K.2,5; Smith, Maree T.1

2021-09-01

10.3390/pharmaceutics13091505

PHARMACEUTICS   影响因子和分区

1999-4923

Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (similar to 400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.

drug delivery system nanoparticles poly (lactic-co-glycolic acid) (PLGA) microfluidic pharmacokinetics (PK) and biodistribution

SCI

英语

其他

National Health and Medical Research Council (NHMRC)["APP1107723","APP1118881","APP1105420"] ; Australian Research Council["LE0775684","LE110100028","LE110100033","LE140100087","LE160100168"]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000701830700001

MDPI

Web of Science

1.Univ Queensland, Fac Med, Sch Biomed Sci, Brisbane, Qld 4072, Australia
2.Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
3.Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China
4.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Peoples R China
5.Univ Queensland, ARC Ctr Excellence Convergent Bio Nano Sci & Tech, Brisbane, Qld 4072, Australia

Han, Felicity Y.,Xu, Weizhi,Kumar, Vinod,et al. Optimisation of a Microfluidic Method for the Delivery of a Small Peptide[J]. PHARMACEUTICS,2021,13(9).

Han, Felicity Y..,Xu, Weizhi.,Kumar, Vinod.,Cui, Cedric S..,Li, Xaria.,...&Smith, Maree T..(2021).Optimisation of a Microfluidic Method for the Delivery of a Small Peptide.PHARMACEUTICS,13(9).

Han, Felicity Y.,et al."Optimisation of a Microfluidic Method for the Delivery of a Small Peptide".PHARMACEUTICS 13.9(2021).