Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media

Hu, Shunwen; Niu, Mengmeng; Hu, Fuqiang; Lü, Yi; Qi, Jianping; Yin, Zongning; Wu, Wei

doi:10.1016/j.ijpharm.2012.10.025

Cited by 149 publications

(94 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Transmission electron microscopy (TEM) Shukla et al, 2008;Mann et al, 2009;Shukla et al, 2010a;Guan et al, 2011;Niu et al, 2011;Shukla et al, 2011;Dai et al, 2013;Premanand et al, 2013;Jain et al, 2014a,b Cryogenic-transmission electron microscopy (Cryo-TEM) Chen et al, 2009 Scanning electron microscopy (SEM) Gebril et al, 2014 Freeze fracture electron microscopy (FFEM) Mann et al, 2006 Separation of free drug from drug-loaded vesicles Molecular exclusion chromatography Singh et al, 2004;Shukla et al, 2008Shukla et al, , 2011Chen et al, 2009;Sun et al, 2010;Guan et al, 2011;Niu et al, 2011Niu et al, , 2012Niu et al, , 2014Dai et al, 2013;Hu et al, 2013;Jain et al, 2014a,b Ultracentrifugation Conacher et al, 2001Song et al, 2005;Mann et al, 2009;Premanand et al, 2013;Gebril et al, 2014 Entrapment efficiency percent High performance liquid chromatography (HPLC) Chen et al, 2009;Sun et al, 2010;Niu et al, 2011Niu et al, , 2012Niu et al, , 2014Hu et reported that increasing either homogenization pressure or cycles reduced the size of BS-liposomes (Chen et al, 2009;Niu et al, 2011). Oppositely, extremely high homogenization pressure increased particle size and PI of BS-vesicles due to rupturing and combination of the vesicles under high h...…”

Section: Morphologymentioning

confidence: 99%

“…Hu et al (2013) reported that SGCliposomes retained most of the insulin load as compared with conventional liposomes in either simulated GI fluids (including pancreatin or pepsin) or in ex vivo GI fluids obtained from rats. The protective effect was credited to the enzymeinhibiting ability of SGC and its associated membrane stabilization aptitude.…”

Section: Stability In Simulated Biological Milieumentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Morphologymentioning

confidence: 99%

Section: Stability In Simulated Biological Milieumentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…These might be attributed to the good deformability of liposomes containing bile salts (Hu et al, 2013). Niu et al (2012) compared the differences between liposomes containing sodium glycocholate, sodium taurocholate and sodium deoxycholate, and the highest oral bioavailability was observed in rats administrated with insulin-loaded sodium glycocholate (8.5 and 11.0% in non-diabetic and diabetic rats, respectively).…”

Section: Paracellular Routementioning

confidence: 99%

“…About 51% blood glucose level reductions were achieved in severely diabetic rats (Kebede et al, 2013). This approach is (Su et al, 2012;Chuang et al, 2013) Bile salts Open the tight junctions and improve deformability and permeation (Degim et al, 2004;Niu et al, 2011Niu et al, , 2012Hu et al, 2013) Enteric coatings HPMCP, Eudragit Õ pH-sensitive Rapid release in intestinal Maroni et al, 2009;Wang & Zhang, 2012;Wu et al 2012a,b,c;Marais et al, 2013;Viehof et al, 2013;Zhao et al, 2013) …”

Section: Natural Polymersmentioning

confidence: 99%

A review of biodegradable polymeric systems for oral insulin delivery

Luo

Xiong

Tian³

et al. 2015

Drug Delivery

View full text Add to dashboard Cite

Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, g-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects.

show abstract

“…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

View full text Add to dashboard Cite

-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.

show abstract

Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media

Cited by 149 publications

References 41 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

A review of biodegradable polymeric systems for oral insulin delivery

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

Contact Info

Product

Resources

About