Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose

Niu, Mengmeng; Lü, Yi; Hovgaard, Lars; Guan, Peipei; Tan, Yanan; Lian, Ruyue; Qi, Jianping; Wu, Wei

doi:10.1016/j.ejpb.2012.02.009

Cited by 180 publications

(116 citation statements)

References 38 publications

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“…In this approach, soybean phosphatidylcholine (SPC) and bile salts were dissolved in ethyl ether to which buffered solution containing insulin was added followed by ultra-sonication to form reverse w/o emulsion (Niu et al, 2011(Niu et al, , 2012(Niu et al, , 2014. The solvent was then removed from the emulsion using a rota-evaporator under reduced pressure.…”

Section: Reverse-phase Evaporation Methodsmentioning

confidence: 99%

“…Reverse-phase evaporation method was used to formulate BSliposomes loaded with insulin (Niu et al, 2011(Niu et al, , 2012(Niu et al, , 2014 or hexamethylmelamine (Sun et al, 2010). In this approach, soybean phosphatidylcholine (SPC) and bile salts were dissolved in ethyl ether to which buffered solution containing insulin was added followed by ultra-sonication to form reverse w/o emulsion (Niu et al, 2011(Niu et al, , 2012(Niu et al, , 2014.…”

Section: Reverse-phase Evaporation Methodsmentioning

confidence: 99%

“…Recently, BS-liposomes have been investigated as stable carriers for delivering sensitive therapeutic agents and proteins by replacing a fraction of the CH in the lipid bilayers with bile salts (Guan et al, 2011;Niu et al, 2011Niu et al, , 2012Niu et al, , 2014. Schematic illustrations of different types of liposomes comprising bile salts in comparison to conventional liposome are presented in Figure 3.…”

Section: Bile Salts-containing Liposomes (Bs-liposomes)mentioning

confidence: 99%

“…Several studies have demonstrated the superiority of BS-liposomes to conventional liposomes in improving the oral absorption of different therapeutic agents and proteins (Chen et al, 2009;Niu et al, 2011). Although the exact underlying mechanisms of oral absorption enhancement of drugs or proteins loaded in BS-liposomes have not been comprehensively elucidated, several authors acknowledged the capability of intact BSliposomes to permeate across the unstirred water layer followed by uptake of the vesicles by membranous epithelial cells (M-cells) in the Payer's patch (Aramaki et al, 1993) and transcellular through enterocytes (Niu et al, 2014) in addition to the facilitated transport through the paracellular pathway (Chen et al, 2009;Niu et al, 2012). Furthermore, it is expected that upon contact with the intestinal epithelial, the included bile salts may increase the membrane fluidity followed by membrane-destabilizing effect, which facilitate internalization of the vesicles (Chen et al, 2009).…”

Section: Bile Salts-containing Liposomes (Bs-liposomes)mentioning

confidence: 99%

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Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Aburahma¹

2014

Drug Delivery

103

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Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BSvesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BSvesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted.

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Section: Reverse-phase Evaporation Methodsmentioning

confidence: 99%

Section: Reverse-phase Evaporation Methodsmentioning

confidence: 99%

Section: Bile Salts-containing Liposomes (Bs-liposomes)mentioning

confidence: 99%

Section: Bile Salts-containing Liposomes (Bs-liposomes)mentioning

confidence: 99%

See 2 more Smart Citations

Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Aburahma¹

2014

Drug Delivery

103

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“…However, the harsh environment in the GIT has negative impact on the oral administration as the presence of physiological BS leads to solubilization of the lipid bilayer (33)(34). The incorporation of BS enhancing the bioavailability of insulin colloidal drug carrier system has previously been reported (35)(36). Thus, the integration of BS in the bilayer membrane might not only function as permeation enhancer, but also as a stabilizing agent to the vesicles preventing premature release of the drug in the harsh environment of the GIT.…”

Section: Introductionmentioning

confidence: 99%

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug

et al. 2017

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-PURPOSE: Liposomes have been studied as a colloidal carrier in drug delivery systems, especially for oral administration. However, their low structural integrity in the gut is still a major shortcoming. Membrane disruptive effects of physiological bile salts in the small intestine result in premature drug release prior to intestinal absorption. Thus, we analyzed the stabilizing effect of sodium deoxycholate when incorporated into nano-sized liposomes. METHOD: Cefotaxime-loaded liposomes were prepared with different sodium deoxycholate concentrations (3.75-30 mM) by rotary film evaporation followed by nanosize reduction. The physical integrity of liposomes was evaluated by monitoring cefotaxime leakage, particle sizes in different simulated physiological media. The oral bioavailability and pharmacokinetics of cefotaxime was assessed in rats (n = 6 per group) after single dose of drug-encapsulated in liposomes containing bile salt, drug in conventional liposomes, and cefotaxime solution (oral and intravenous). RESULTS: Simulated gastric fluid with low pH showed less effect on the stability of liposomes in comparison to media containing physiological bile salts. Liposomes containing 15 mM sodium deoxycholate were most stable in size and retained the majority of encapsulated cefotaxime even in fed state of simulated intestinal fluid being the most destructive media. Pharmacokinetics data showed an increase in Cmax and AUC0-inf in the following order: cefotaxime solution < conventional liposomes < liposomes made with bile salts. The total oral bioavailability of cefotaxime in liposomes containing bile salt was found to be 5-times higher compared to cefotaxime solution and twice as much as in conventional liposomes. CONCLUSION: Incorporation of bile salts, initially used as membrane permeation enhancer, also acted as a stabilizer against physiological bile salts. The nanosized liposomes containing sodium deoxycholate were able to reduce the leakage of encapsulated cefotaxime in the gut due to the improved vesicle stability and to enhance the oral bioavailability of acid-labile drugs up to 5-fold.

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Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers

Wang

Yang

Fan

et al. 2018

Adv Healthcare Materials

100

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Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24‐ and 7.91‐fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers.

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Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: The effect of cholate type, particle size and administered dose

Cited by 180 publications

References 38 publications

Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug

Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers

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