Mucosal Penetrative Polymeric Micelle Formulations for Insulin Delivery to the Respiratory Tract.

Autor: Kang JH; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea.; School of Pharmacy, Institute of New Drug Development, and Respiratory Drug Development Research Institute, Jeonbuk National University, Jeonju, Republic of Korea., Jeong JH; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea., Kwon YB; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea., Kim YJ; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea., Shin DH; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea., Park YS; Research & Development Center, P2K Bio, Cheongju, Republic of Korea., Hyun S; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea., Kim DW; College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea., Park CW; College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea.
Jazyk: angličtina
Zdroj: International journal of nanomedicine [Int J Nanomedicine] 2024 Sep 07; Vol. 19, pp. 9195-9211. Date of Electronic Publication: 2024 Sep 07 (Print Publication: 2024).
DOI: 10.2147/IJN.S474287
Abstrakt: Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers.
Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract.
Results: The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (C max ) and AUC 0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h.
Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.
Competing Interests: The authors report no conflicts of interest in this work.
(© 2024 Kang et al.)
Databáze: MEDLINE
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