Probucol Release from Novel Multicompartmental Microcapsules for the Oral Targeted Delivery in Type 2 Diabetes

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2014 Aug 30

PMID 25168450

Citations 21

Authors

Armin Mooranian

Rebecca Negrulj

Hesham S Al-Sallami

Zhongxiang Fang

Momir Mikov

Svetlana Golocorbin-Kon

Marc Fakhoury

Gerald F Watts

Vance Matthews

Frank Arfuso

Amanda Lambros

Hani Al-Salami

Affiliations

Soon will be listed here.

Abstract

In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6 ± 0.25% PB content, and zeta potential of -66 ± 1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p < 0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85 ± 5 and 92 ± 2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules.

Citing Articles

Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, Placebo-Controlled Clinical Study.

Lakic B, Skrbic R, Uletilovic S, Mandic-Kovacevic N, Grabez M, Saric M J Diabetes Res. 2024; 2024:4187796.

PMID: 38455850 PMC: 10919985. DOI: 10.1155/2024/4187796.

Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.

Jones M, Ionescu C, Walker D, Wagle S, Kovacevic B, Chester J Int J Mol Sci. 2022; 23(2).

PMID: 35055022 PMC: 8775521. DOI: 10.3390/ijms23020836.

Artificial Cell Encapsulation for Biomaterials and Tissue Bio-Nanoengineering: History, Achievements, Limitations, and Future Work for Potential Clinical Applications and Transplantation.

Mooranian A, Jones M, Ionescu C, Walker D, Wagle S, Kovacevic B J Funct Biomater. 2021; 12(4).

PMID: 34940547 PMC: 8704355. DOI: 10.3390/jfb12040068.

The Effects of Primary Unconjugated Bile Acids on Nanoencapsulated Pharmaceutical Formulation of Hydrophilic Drugs: Pharmacological Implications.

Mooranian A, Foster T, Ionescu C, Carey L, Walker D, Jones M Drug Des Devel Ther. 2021; 15:4423-4434.

PMID: 34720580 PMC: 8550211. DOI: 10.2147/DDDT.S328526.

Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant.

Mooranian A, Ionescu C, Wagle S, Kovacevic B, Walker D, Jones M Pharmaceutics. 2021; 13(10).

PMID: 34684006 PMC: 8538409. DOI: 10.3390/pharmaceutics13101713.

References

Awasthi R, Kulkarni G . Development of novel gastroretentive drug delivery system of gliclazide: hollow beads. Drug Dev Ind Pharm. 2013; 40(3):398-408. DOI: 10.3109/03639045.2013.763817. View

Zimetbaum P, Eder H, Frishman W . Probucol: pharmacology and clinical application. J Clin Pharmacol. 1990; 30(1):3-9. DOI: 10.1002/j.1552-4604.1990.tb03431.x. View

Caesar R, Fak F, Backhed F . Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med. 2010; 268(4):320-8. DOI: 10.1111/j.1365-2796.2010.02270.x. View

Yamashita S, Matsuzawa Y . Where are we with probucol: a new life for an old drug?. Atherosclerosis. 2009; 207(1):16-23. DOI: 10.1016/j.atherosclerosis.2009.04.002. View

Shimizu H, Uehara Y, Shimomura Y, Tanaka Y, Kobayashi I . Probucol attenuated hyperglycemia in multiple low-dose streptozotocin-induced diabetic mice. Life Sci. 1991; 49(18):1331-8. DOI: 10.1016/0024-3205(91)90197-j. View

Al-Kassas R, Al-Gohary O, Al-Faadhel M . Controlling of systemic absorption of gliclazide through incorporation into alginate beads. Int J Pharm. 2007; 341(1-2):230-7. DOI: 10.1016/j.ijpharm.2007.03.047. View

Efentakis M, Buckton G . The effect of erosion and swelling on the dissolution of theophylline from low and high viscosity sodium alginate matrices. Pharm Dev Technol. 2002; 7(1):69-77. DOI: 10.1081/pdt-120002232. View

Nourooz-Zadeh J, Gopaul N, Forster L, Ferns G, Anggard E . Measurement of plasma probucol levels by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1994; 654(1):55-60. DOI: 10.1016/0378-4347(94)00003-4. View

Al-Salami H, Butt G, Tucker I, Golocorbin-Kon S, Mikov M . Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats. Eur J Drug Metab Pharmacokinet. 2011; 37(2):99-108. DOI: 10.1007/s13318-011-0060-y. View

10.

Cani P, Possemiers S, Van de Wiele T, Guiot Y, EVERARD A, Rottier O . Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009; 58(8):1091-103. PMC: 2702831. DOI: 10.1136/gut.2008.165886. View

11.

Mikov M, Fawcett J, Kuhajda K, Kevresan S . Pharmacology of bile acids and their derivatives: absorption promoters and therapeutic agents. Eur J Drug Metab Pharmacokinet. 2006; 31(3):237-51. DOI: 10.1007/BF03190714. View

12.

Wu R, Zhang W, Liu B, Gao J, Xiao X, Zhang F . Probucol ameliorates the development of nonalcoholic steatohepatitis in rats fed high-fat diets. Dig Dis Sci. 2012; 58(1):163-71. DOI: 10.1007/s10620-012-2335-9. View

13.

Goldfine A, Fonseca V, Shoelson S . Therapeutic approaches to target inflammation in type 2 diabetes. Clin Chem. 2010; 57(2):162-7. PMC: 3227024. DOI: 10.1373/clinchem.2010.148833. View

14.

George M, Abraham T . Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan--a review. J Control Release. 2006; 114(1):1-14. DOI: 10.1016/j.jconrel.2006.04.017. View

15.

Huang X, Brazel C . On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001; 73(2-3):121-36. DOI: 10.1016/s0168-3659(01)00248-6. View

16.

Mladenovska K, Cruaud O, Richomme P, Belamie E, Raicki R, Venier-Julienne M . 5-ASA loaded chitosan-Ca-alginate microparticles: Preparation and physicochemical characterization. Int J Pharm. 2007; 345(1-2):59-69. DOI: 10.1016/j.ijpharm.2007.05.059. View

17.

Cani P, Neyrinck A, Fava F, Knauf C, Burcelin R, Tuohy K . Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007; 50(11):2374-83. DOI: 10.1007/s00125-007-0791-0. View

18.

Duboc H, Rajca S, Rainteau D, Benarous D, Maubert M, Quervain E . Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2012; 62(4):531-9. DOI: 10.1136/gutjnl-2012-302578. View

19.

Yang L, Zhang H, Mikov M, Tucker I . Physicochemical and biological characterization of monoketocholic acid, a novel permeability enhancer. Mol Pharm. 2009; 6(2):448-56. DOI: 10.1021/mp800143w. View

20.

Duro R, Alvarez C, Martinez-Pacheco R, Gomez-Amoza J, Concheiro A, Souto C . The adsorption of cellulose ethers in aqueous suspensions of pyrantel pamoate: effects on zeta potential and stability. Eur J Pharm Biopharm. 1998; 45(2):181-8. DOI: 10.1016/s0939-6411(97)00103-3. View