Development of a hydroxypropyl methyl cellulose/polyacrylic acid interpolymer complex formulated buccal mucosa adhesive film to facilitate the delivery of insulin for diabetes treatment

被引：2

作者：

Chen, Yi ^{[1
]}

Zhang, Lili ^{[1
]}

Xu, Jinzhuan ^{[1
,2
]}

Xu, Shan ^{[1
]}

Li, Yi ^{[1
]}

Sun, Runbin ^{[3
]}

Huang, Jing ^{[1
]}

Peng, Jianqing ^{[1
]}

Gong, Zipeng ^{[1
,2
]}

Wang, Jianta ^{[1
]}

Tang, Lei ^{[1
]}

机构：

[1] Guizhou Med Univ, Guizhou Prov Engn Technol Res Ctr Chem Drug R&D, Sch Pharmaceut Sci, State Key Lab Funct & Applicat Med Plants, Guiyang 561113, Peoples R China

[2] Guizhou Med Univ, Guizhou Prov Key Lab Pharmaceut, Guiyang 561113, Peoples R China

[3] Nanjing Univ, Nanjing Drum Tower Hosp, Phase 1 Clin Trials Unit, Affiliated Hosp,Med Sch, Nanjing 210008, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2024年 / 269卷

基金：

中国国家自然科学基金;

关键词：

Hydroxypropyl methylcellulose/polyacrylic; acid interpolymer complex; Buccal mucosa; Insulin; PHASE-BEHAVIOR; ORAL DELIVERY; NANOPARTICLES;

D O I：

10.1016/j.ijbiomac.2024.131876

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Buccal mucosa administration is a promising method for insulin (INS) delivery with good compliance. However, buccal mucosa delivery systems still face challenges of long-term mucosal adhesion, sustained drug release, and mucosal drug penetration. To address these issues, a double-layer film consisting of a hydroxypropyl methylcellulose/polyacrylic acid interpolymer complex (IPC)-formulated mucoadhesive layer and an ethylcellulose (EC)-formulated waterproof backing layer (IPC/EC film) was designed. Protamine (PTM) and INS were co-loaded in the mucoadhesive layer of the IPC/EC film (PTM-INS-IPC/EC film). In ex vivo studies with porcine buccal mucosa, this film exhibited robust adhesion, with an adhesion force of 120.2 +/- 20.3 N/m2 and an adhesion duration of 491 +/- 45 min. PTM has been shown to facilitate INS mucosal transfer. Pharmacokinetic studies indicated that the PTM-INS-IPC/EC film significantly improved the absorption of INS, exhibiting a 1.45 and 2.24fold increase in the area under the concentration-time curve (AUC0-infinity) compared to the INS-IPC/EC film and free INS, respectively. Moreover, the PTM-INS-IPC/EC film effectively stabilized the blood glucose levels of type 1 diabetes mellitus (T1DM) rats with post oral glucose administration, maintaining lower glucose levels for approximately 8 h. Hence, the PTM-INS-IPC/EC film provides a promising noninvasive INS delivery system for diabetes treatment.

引用

页数：13