Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Intestinal Absorption of Insulin Using the In Situ Closed-Loop Method
2.3. Estimation of Intestinal Membrane Damage
2.4. Circular Dichroism Studies
2.5. Preparation of Rat Mucosal Tissue Homogenates
2.6. Degradation of Insulin in Intestinal Mucosal Homogenates
2.7. Measurement of Transepithelial Electrical Resistance (TEER) and Transport of Insulin Using Caco-2 Cell Monolayers
2.8. Analytical Methods
2.9. Statistical Analyses
3. Results
3.1. Effects of Labrasol® and Its Related Formulations on the Intestinal Absorption of Insulin and Their Intestinal Membrane Toxicity
3.2. Absorption Enhancing Characteristics of Capryol 90
3.3. Effect of Capryol 90 on the Association Properties of Insulin
3.4. Effect of Capryol 90 on the Stability of Insulin in Intestinal Homogenates
3.5. Effects of Capryol 90 on TEER and Insulin Transport in Caco-2 Cell Monolayers
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Product Name | Chemical Definition | Hydrophobic Group |
---|---|---|
Labrasol® | Caprylocaproyl macrogol-8 glycerides | caproic acid (≤2.0%), caprylic acid (50–80%), capric acid (20.0–50.0%), lauric acid (≤3.0%), myristic acid (≤1.0%) |
Caprylocaproyl polyoxyl-8 glycerides | ||
Capryol 90 | Propylene glycol monocaprylate (type ii) | caprylic acid (≥90%), capric acid (≤3.0%), lauric acid (≤3.0%), myristic acid (≤3.0%), palmitic acid (≤1.0%) |
Capryol PGMC | Propylene glycol monocaprylate (type i) | caprylic acid (≥99%), capric acid (≤3.0%), lauric acid (≤3.0%) |
Lauroglycol 90 | Propylene glycol monolaurate (type ii) | caprylic acid (≤0.5%), capric acid (≤2.0%), lauric acid (≥95.0%), myristic acid (≤3.0%), palmitic acid (≤1.0%) |
Lauroglycol FCC | Propylene glycol monolaurate (type i) | caprylic acid (≤0.5%), capric acid (≤2.0%), lauric acid (≥95.0%), myristic acid (≤3.0%), palmitic acid (≤1.0%) |
Labrafil M 2125 CS | Linoleoyl macrogol-6 glycerides | palmitic acid (4.0–20.0%), stearic acid (≤6.0%),oleic acid (20.0–35.0%), linoleic acid (50.0–65.0%), linolenic acid (≤2.0%), arachidic acid (≤1.0%), eicosenoic acid (≤1.0%) |
Linoleoyl polyoxyl-6 glycerides | ||
Maisine 35-1 | Glycerol monolinoleate | palmitic acid (4.0–20.0%), stearic acid (≤6.0%), oleic acid (10.0–35.0%), linoleic acid (≥50.0%), linolenic acid (≤2.0%), arachidic acid (≤1.0%), eicosenoic acid (≤1.0%) |
Glyceryl monolinoleate |
Formulation | Concentration (% v/v) | AAC0→4h (%⋅min) | PA% | Enhancement Ratio |
---|---|---|---|---|
Control | - | 636 ± 636 | 0.10 ± 0.10 | - |
+ Labrasol® | 10 | 5700 ± 130 ** | 0.87 ± 0.02 ** | 9.0 |
+ Capryol 90 | 5 | 1040 ± 550 | 0.16 ± 0.08 | 1.6 |
10 | 8050 ± 703 ** | 1.23 ± 0.11 ** | 12.7 | |
15 | 9870 ± 2740 ** | 1.51 ± 0.42 ** | 15.5 | |
+ Capryol PGMC | 10 | 2750 ± 1100 | 0.42 ± 0.17 | 4.3 |
+ Lauroglycol 90 | 10 | 5700 ± 1350 ** | 0.87 ± 0.21 ** | 9.0 |
+ Lauroglycol FCC | 10 | 844 ± 286 | 0.13 ± 0.04 | 1.3 |
+ Labrafil M 2125 CS | 10 | 10 ± 10 | 0.002 ± 0.002 | 0.02 |
+ Maisine 35-1 | 10 | 1110 ± 1100 | 0.17 ± 0.17 | 1.7 |
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Ukai, H.; Iwasa, K.; Deguchi, T.; Morishita, M.; Katsumi, H.; Yamamoto, A. Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery. Pharmaceutics 2020, 12, 462. https://doi.org/10.3390/pharmaceutics12050462
Ukai H, Iwasa K, Deguchi T, Morishita M, Katsumi H, Yamamoto A. Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery. Pharmaceutics. 2020; 12(5):462. https://doi.org/10.3390/pharmaceutics12050462
Chicago/Turabian StyleUkai, Hiroki, Kazuki Iwasa, Takamasa Deguchi, Masaki Morishita, Hidemasa Katsumi, and Akira Yamamoto. 2020. "Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery" Pharmaceutics 12, no. 5: 462. https://doi.org/10.3390/pharmaceutics12050462
APA StyleUkai, H., Iwasa, K., Deguchi, T., Morishita, M., Katsumi, H., & Yamamoto, A. (2020). Enhanced Intestinal Absorption of Insulin by Capryol 90, a Novel Absorption Enhancer in Rats: Implications in Oral Insulin Delivery. Pharmaceutics, 12(5), 462. https://doi.org/10.3390/pharmaceutics12050462