Trypsin decorated self-emulsifying drug delivery systems (SEDDS): Key to enhanced mucus permeation

Shahzadi, Iram; Dizdarević, Aida; Efiana, Nuri Ari; Matuszczak, Barbara; Bernkop‐Schnürch, Andreas

doi:10.1016/j.jcis.2018.07.057

Cited by 38 publications

(24 citation statements)

References 33 publications

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“… 8 , 9 Moreover, as the vast majority of SEDDS contain PEG-ylated surfactants forming a muco-inert PEG-corona around the oily droplets, they are able to permeate the mucus gel barrier in a comparatively efficient manner enabling the transport of incorporated drugs to the underlying absorption membrane. 10 − 12 …”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…For the development of NCs, an as low as feasible concentration of PG was used to dissolve HIPs in NCs, as this hydrophilic co-solvent is immediately released from the lipophilic phase in aqueous media promoting the release of HIPs out of the oily droplets [14]. Exenatide release from NCs was characterized based on the affinity of HIPs toward the oily phase of NCs and the release medium [25]. A log D of at least 2 has been demanded to keep ≥ 50% of HIPs in NCs [14].…”

Section: Discussionmentioning

confidence: 99%

“…The release characteristics of exenatide-THA and exenatide-DOC from the nanocarriers were evaluated by determining the distribution of the ion pairs between the lipophilic phase of the NCs and the release medium (log D LPh/RM ) [25,26]. Lyophilized exenatide-THA (molar ratio 1:8) and exenatide-DOC (molar ratio 1:4) were dispersed in simulated intestinal fluid (50 mM phosphate buffer pH 6.8), HBSS and the lipophilic phase of the NC.…”

Section: Determination Of Log D Lipophilic Phase (Lph)/release Mediummentioning

confidence: 99%

“…As the released HIPs are absorbed from the membrane, more HIPs will diffuse out of the nanodroplets until equilibrium is reached again. Since drug release is controlled by the partition coefficient of HIPs between the lipophilic phase (LPh) and the release medium (RM) that should mimic gastrointestinal conditions, log D LPh/ RM was determined in two different aqueous media [25,26]. Log D LPh/ RM of exenatide-THA was 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 HBSS, respectively.…”

Section: Determination Of Log D Of Exenatide-tha and Exenatide-docmentioning

confidence: 99%

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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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“…[ 185 ] NCs decorated with mucolytic enzymes such as papain, bromelain, and trypsin were shown to exhibit highly improved mucus diffusivity. [ 186–188 ]…”

Section: Interactive Surface Propertiesmentioning

confidence: 99%

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Friedl

Nele

Rosa

et al. 2021

Adv Funct Materials

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Nanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off‐target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. These key surface properties—bioinert and stealth versus interactive at the target site—are in contradiction to each other so that the best compromise between them has to be found. Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. Stimuli‐responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.

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Trypsin decorated self-emulsifying drug delivery systems (SEDDS): Key to enhanced mucus permeation

Cited by 38 publications

References 33 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

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

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

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