In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

Kontogiannidou, Eleni; Meikopoulos, Thomas; Gika, Helen; Panteris, Emmanuel; Vizirianakis, Ioannis S.; Müllertz, Anette; Fatouros, Dimitrios G.

doi:10.3390/pharmaceutics12080699

Cited by 28 publications

(12 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 57 , 58 This property enhances chyle particle production as well as lymphatic transport of drug and avoids drug degradation by first-pass hepatic metabolism, by which reasons the bioavailability of the drug can be improved. 47 , 59 Hence, for the purposes of achieving optimum drug loading, forming the smallest particle sizes and improving lymphatic transport of GKA, Maisine CC was selected as the oil phase in GKA-SNEDDS.…”

Section: Discussionmentioning

confidence: 99%

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Yin¹,

Yin²,

Ouyang³

et al. 2021

DDDT

View full text Add to dashboard Cite

Purpose The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA. Methods We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model. Results The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model. Conclusion Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.

show abstract

Section: Discussionmentioning

confidence: 99%

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Yin¹,

Yin²,

Ouyang³

et al. 2021

DDDT

View full text Add to dashboard Cite

show abstract

“…To overcome these limitations, various lipid-based nano-formulations were previously reported for the enhancement of solubility, bioavailability, and oral efficacy. The delivery systems like solid lipid nanoparticles [12], nanostructure lipid carriers [13], liposomes [14], niosomes [15], and self-nanoemulsifying drug delivery systems [16,17] have shown the potential for the enhancement of solubility and bioavailability. Among these, SNEDDS is the most prominent and novel formulation approach for the oral delivery of poorly soluble therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

et al. 2021

View full text Add to dashboard Cite

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

show abstract

“…For comparison, after 3 h of incubation at the highest concentration (5 μM), AmB-OA SNEDDS resulted in an ∼2.8-fold increase in drug transport compared to AmB-OA and an ∼63.3-fold increase in drug transport compared to AmB. These results were remarkably higher than previously published reports of AmB SNEDDS. − Distinct enhancement in permeation of AmB-OA SNEDDS could be the combined effect of improved lipophilicity of prodrug, enhanced Caco-2 cell internalization offered by nanometer sized (<100 nm) emulsion droplet, the opening of tight cellular junctions, and p-gp efflux inhibition offered by bioactive formulation components such as Camul MCM C8 and Cremophor RH 40. , These observations highlighted the role of prodrug formation and nanoformulation in improving drug permeation.…”

Section: Results and Discussionmentioning

confidence: 78%

“…There are few reports available that explored the potential of AmB SNEDDS to improve the oral bioavailability. − However, these approaches attained limited success because of the poor solubility of AmB in oils, the very low intestinal permeability of AmB in native form, and its instability in GIT. Also, a majority of reports related to oral AmB SNEDDS formulation have limited their research exploration to in vitro studies and have not extensively analyzed critical formulation attributes such as accelerated stability study at tropical stress conditions, in vivo pharmacokinetic analysis, and in vivo toxicity testing.…”

Section: Introductionmentioning

confidence: 99%

Enabling Oral Amphotericin B Delivery by Merging the Benefits of Prodrug Approach and Nanocarrier-Mediated Drug Delivery

Thanki

Date

Jain

2021

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Amphotericin B (AmB) is gold standard therapy for leishmaniasis and fungal infections. Considering the global disease burden, nearly 90% of cases occur in economically vulnerable countries, making the cost of AmB therapy a critical healthcare challenge in controlling disease burden. All currently marketed AmB products are administered through an intravenous (i.v.) route and involve high treatment costs. Designing an orally effective AmB formulation can substantially reduce the cost of therapy and improve patient compliance. However, it is a challenging task because of the distinctive physicochemical properties of AmB. Previously, we developed a lipid-based prodrug of AmB, AmB-oleyl conjugate (AmB-OA), which showcased remarkable stability in the gastrointestinal (GI) environment and improved intestinal permeation. Hereby, we have developed self-nanoemulsifiying drug delivery system (SNEDDS) of AmB-OA to further enhance the oral bioavailability of AmB and potentiate its therapeutic benefits. SNEDDS was developed by screening a wide range of oils, surfactants, and cosurfactants, and formulation composition was optimized using extreme vertices design. AmB-OA SNEDDS possessed the ability of quick self-nanoemulsification on dilution (droplet size ∼56 nm) along with remarkable stability in the GI environment. Accelerated stability (40 °C/75% relative humidity) studies and freeze–thaw cycling studies proved that the formulation was stable at tropical conditions as well as temperature cycling stress. Drug transport analysis in Caco-2 cells revealed a remarkable increase in drug transport for AmB-OA SNEDDS compared to AmB along with minimal cellular toxicities. AmB-OA SNEDDS showcased ∼8.9-fold higher AUCTot than AmB in in vivo pharmacokinetic study, proving the effectiveness of formulation to enhance oral bioavailability. In vivo toxicity analysis highlighted the ameliorated toxicity risk associated with SNEDDS formulation. Therefore, the AmB-OA SNEDDS formulation may provide a cost-friendly and effective strategy to resolve the oral AmB drug delivery challenge.

show abstract

In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

Cited by 28 publications

References 40 publications

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer

Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Enabling Oral Amphotericin B Delivery by Merging the Benefits of Prodrug Approach and Nanocarrier-Mediated Drug Delivery

Contact Info

Product

Resources

About