Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Lam, Hung Thanh; Le‐Vinh, Bao; Phan, Thi Nhu Quynh; Bernkop‐Schnürch, Andreas

doi:10.1111/jphp.13021

Cited by 46 publications

(23 citation statements)

References 32 publications

(111 reference statements)

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“…The size distribution of complex loaded SEDDS FB was in the range of 40 ± 10 nm as described in Figure 3 B. Lam et al also observed an increase in the size of oily droplets by incorporation of cationic surfactants as the mean droplet size of SEDDS increased from 31 to 45 nm by incorporation of 1% 1-decyl-3-methylimidazolium chloride and to 55 nm by the incorporation of 5% octylamine. 26 During the incubation period neither precipitation nor phase separation of formulations was observed. The size distribution of the oily droplets of all formulations remained constant, the and PDI remained under 0.5 indicating monodisperse emulsions during the incubation time.…”

Section: Resultsmentioning

confidence: 98%

“…The tertiary amine surfactant octylamine could not raise the zeta potential of SEDDS to a positive value even when added in a concentration of 5%, whereas the incorporation of 1% quaternary ammonium surfactants caused a dramatic shift in zeta potential to positive values. 26 To a certain extent CTL–polymer complexes seem to be located on the interface, as their incorporation in SEDDS had a significant impact on the zeta potential of the resulting oily droplets. Generally, SEDDS remained stable in the release medium despite size and zeta potential alterations caused by incorporating CTL–polymer complexes.…”

Section: Resultsmentioning

confidence: 99%

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Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

et al. 2020

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The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5′-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

et al. 2020

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“…Another possibility to optimize the formulation could be to change the cationic surfactant to one that has shown a lower cytotoxicity at the same concentration. Cationic surfactants such as alkyltrimethylammonium bromide, octylamine and 1-decyl-3-methylimidazolium have recently shown a lower cytotoxicity than benzalkonium chloride and its possible to design and prepare systems with nanometric size using these surfactants [36].…”

Section: Resultsmentioning

confidence: 99%

Hyaluronic Acid Nanocapsules as a Platform for Needle-Free Vaccination

2019

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Vaccination faces many challenges nowadays, and among them the use of adjuvant molecules and needle-free administration are some of the most demanding. The combination of transcutaneous vaccination and nanomedicine through a rationally designed new-formulation could be the solution to this problem. This study focuses on this rational design. For this purpose, new hyaluronic acid nanocapsules (HA-NCs) have been developed. This new formulation has an oily nucleus with immunoadjuvant properties (due to α tocopherol) and a shell made of hyaluronic acid (HA) and decorated with ovalbumin (OVA) as the model antigen. The resulting nanocapsules are smaller than 100 nm, have a negative superficial charge and have a population that is homogeneously distributed. The systems show high colloidal stability in storage and physiological conditions and high OVA association without losing their integrity. The elevated interaction of the novel formulation with the immune system was demonstrated through complement activation and macrophage viability studies. Ex vivo studies using a pig skin model show the ability of these novel nanocapsules to penetrate and retain OVA in higher quantities in skin when compared to this antigen in the control solution. Due to these findings, HA-NCs are an interesting platform for needle-free vaccination.

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“…In vitro hemolysis assay with exenatide-THA and exenatide-DOC as well as blank NCs was performed according to a previously reported protocol [27]. The dilution of 0.556 ml of human whole blood with 1.944 ml of sterile Dulbecco's PBS pH 7.4 was performed.…”

Section: In Vitro Hemolysis Assaymentioning

confidence: 99%

“…The in vitro hemolysis assay on human erythrocytes can be used as a rapid and reliable method to evaluate the effect of drug delivery systems on cell membranes [27,29]. In comparison to other cell types, the cell membrane of erythrocytes is very fragile.…”

Section: Cytocompatibilitymentioning

confidence: 99%

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Ismail

Phan

Laffleur

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log D lipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log D LPh/RM of exenatide-DOC was 1.2 and −0.9 in simulated intestinal fluid and Hanks' balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.

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Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Cited by 46 publications

References 32 publications

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

Hyaluronic Acid Nanocapsules as a Platform for Needle-Free Vaccination

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

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