A nanoemulsion/micelles mixed nanosystem for the oral administration of hydrophobically modified insulin

被引:20
|
作者
Santalices, Irene [1 ,2 ]
Vazquez-Vazquez, Carlos [3 ]
Santander-Ortega, Manuel J. [4 ,5 ]
Lozano, Victoria [4 ,5 ]
Araujo, Francisca [6 ]
Sarmento, Bruno [6 ,7 ]
Shrestha, Neha [8 ]
Preat, Veronique [8 ]
Chenlo, Miguel [9 ]
Alvarez, Clara, V [9 ]
Benetti, Federico [10 ]
Cunarro, Juan [1 ]
Tovar, Sulay [1 ]
Torres, Dolores [2 ]
Jose Alonso, Maria [1 ,2 ]
机构
[1] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Campus Vida, Santiago De Compostela 15782, Spain
[2] Univ Santiago de Compostela, Sch Pharm, Dept Pharmaceut & Pharmaceut Technol, Campus Vida, Santiago De Compostela 15782, Spain
[3] Univ Santiago de Compostela, Fac Chem, Dept Phys Chem, Campus Vida, Santiago De Compostela 15782, Spain
[4] Univ Castilla La Mancha, Sch Pharm, Cellular Neuroanat & Mol Chem Cent Nervous Syst G, Albacete 02071, Spain
[5] Univ Castilla La Mancha, Reg Ctr Biomed Res CRIB, Albacete 02071, Spain
[6] Univ Porto, Inst Invest & Inovacao Saude I3S, Inst Nacl Engn Biomed INEB, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[7] Inst Invest & Formacao Avancada Ciencias & Tecnol, P-4585116 Gandra, Portugal
[8] Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, B-1200 Brussels, Belgium
[9] Univ Santiago de Compostela, Ctr Res Mol Med & Chron Dis CIMUS, Neoplasia & Endocrine Differentiat Grp, Campus Vida 15782, Santiago De Compostela, Spain
[10] ECAMRICERT SRL, ECSIN European Ctr Sustainable Impact Nanotechnol, Padua, Italy
关键词
Oral; Peptide; Insulin; Nanocarrier; Nanoemulsion; Micelles; BILE-SALTS; PARTICLE TRACKING; NANOCAPSULES; DRUG; DELIVERY; CARRIERS; CALCITONIN; STABILITY; CHITOSAN; PEG;
D O I
10.1007/s13346-021-00920-x
中图分类号
TH7 [仪器、仪表];
学科分类号
0804 ; 080401 ; 081102 ;
摘要
The potential of nanoemulsions for the oral administration of peptides is still in its early stage. The aim of the present work was to rationally design, develop, and fully characterize a new nanoemulsion (NE) intended for the oral administration of hydrophobically modified insulin (HM-insulin). Specific components of the NE were selected based on their enhancing permeation properties as well as their ability to improve insulin association efficiency ( Miglyol 812, sodium taurocholate), stability in the intestinal fluids, and mucodiffusion (PEGylated phospholipids and poloxamer 407). The results showed that the NE co-existed with a population of micelles, forming a mixed system that exhibited a 100% of HM-insulin association efficiency. The nanosystem showed good stability and miscibility in different bio-relevant media and displayed an acceptable mucodiffusive behavior in porcine mucus. In addition, it exhibited a high interaction with cell mono-cultures (Caco-2 and C2BBe1 human colon carcinoma Caco-2 clone cells) and co-cultures (C2BBe1 human colon carcinoma Caco-2 clone/HT29-MTX cells). The internalization in Caco-2 monolayers was also confirmed by confocal microscopy. Finally, the promising in vitro behavior of the nanosystem in terms of overcoming the biological barriers of the intestinal tract was translated into a moderate, although significant, hypoglycemic response (approximate to 20-30%), following intestinal administration to both healthy and diabetic rat models. Overall, this information underlines the crucial steps to address when designing peptide-based nanoformulations to successfully overcome the intestinal barriers associated to the oral modality of administration.
引用
收藏
页码:524 / 545
页数:22
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