Mucus permeating self-emulsifying drug delivery systems (SEDDS): About the impact of mucolytic enzymes

Efiana, Nuri Ari; Phan, Thi Nhu Quynh; Wicaksono, Arko Jatmiko; Schnürch, Andreas Bernkop

doi:10.1016/j.colsurfb.2017.10.032

Cited by 33 publications

(23 citation statements)

References 26 publications

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“…The study showed the diffusion of SEDDS with no lipids was higher than the diffusion of other tested systems [151]. Similarly, the same group used the rotary tube technique to understand the influence of different mucolytic agents on the relative movement of a SEDDS consisting of Captex 355 (Capric Triglyceride), Kolliphor EL and propylene glycol [152]. This study showed that the SEDDS loaded with papain had a higher diffusion through mucus compared with the same system loaded with other mucolytic agents.…”

Section: Zupancˇicˇ Et Al Utilized This Technique To Study the Permementioning

confidence: 85%

“…A more exhaustive study to understand the effect of mucolytic agents like bromelain, papain and trypsin was conducted by Efiana et al [125]. The enzymes were ion paired with a hydrophobic surfactant (palmitoyl chloride) with a maximum conjugation of up to 47.8% for papain compared with other peptides.…”

Section: Other Strategies To Improve Mucus Permeation Of Sedds: Mucolmentioning

confidence: 99%

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Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

Abdulkarim

Sharma

Gumbleton

2019

Advanced Drug Delivery Reviews

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Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.

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Section: Zupancˇicˇ Et Al Utilized This Technique To Study the Permementioning

confidence: 85%

Section: Other Strategies To Improve Mucus Permeation Of Sedds: Mucolmentioning

confidence: 99%

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

Abdulkarim

Sharma

Gumbleton

2019

Advanced Drug Delivery Reviews

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“…Moreover, the use of non-ionic surfactants was necessary. However, further analyses were necessary to refine the surfactant choice to a PEGylated type, such as the Kolliphor type reported to show a negative droplet surface charge [ 39 , 40 ]. Additionally, we observed well-adapted zeta-potential changes corresponding to the added concentrations of cationic polymers dissolved in these micellar surfactants.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, the zeta potential exhibited by nanodroplets strongly influences their muco-permeation. The composition of mucin fibers from negatively charged proteoglycans forming the mucus displays selectivity towards the positively charged droplets electrostatically interacting with the mucus, causing major entrapment and poor permeation [ 8 , 39 ]. On the contrary, the diffusion of neutral or particularly negatively charged droplets repelling electrostatic interactions with the mucus is favorable [ 8 ].…”

Section: Resultsmentioning

confidence: 99%

Dual-Acting Zeta-Potential-Changing Micelles for Optimal Mucus Diffusion and Enhanced Cellular Uptake after Oral Delivery

2021

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Context: Overcoming the intestinal mucosal barrier can be a challenge in drug delivery. Nanoemulsions with negative zeta potentials can effectively permeate the mucus layer, but those with positive zeta potentials are better taken up by cells; a nanoemulsion with capricious zeta potential from negative to positive can achieve both good permeation and high uptake. Objective: This study aimed to develop dual-acting zeta-potential-amphoteric micelles enabling optimal muco-permeation and enhancement of cellular uptake. Methods: A micellar pre-concentrate was prepared from 15% Labrasol, 15% Kolliphor EL, 30% Kolliphor RH 40, and 40% dimethylsulfoxide. The micellar pre-concentrate was loaded with anionic stearic acid (SA), forming ionic complexes with cationic polymers at a ratio of 25:1 with Eudragit RS 100 and Eudragit RL 100. Blank micelles and those containing complexes were separately diluted in physiological buffers and examined for their droplet sizes, polydispersity indices (PDIs), zeta potentials, and cytotoxicity. The SA release from the micellar complexes was evaluated in 0.1 mM phosphate buffer (pH 6.8) containing 0.001% fluorescein, thereby enabling an instant decrease in fluorescence. Finally, the micelles were loaded with the model drug fluorescein diacetate (FDA) and evaluated for their muco-permeation behavior and cellular uptake. Results: The micellar dilutions formed micelles at the critical micelle concentration (CMC) of 312 µg/mL and showed a uniform average droplet size of 14.2 nm, with a PDI < 0.1. Micellar dilutions were non-cytotoxic when used at 1:100 in a physiological medium. Micelles loaded with ionic complexes achieved a sustained release of 95.5 ± 3.7% of the SA in 180 min. Moreover, the zeta potential of the complex-loaded micelles shifted from −5.4 to +1.8 mV, whereas the blank micelles showed a stabilized zeta potential of −10 mV. Furthermore, the negatively charged blank and complex-loaded micelles exhibited comparable muco-permeation, with an overall average of 58.2 ± 3.7% diffusion of FDA. The complex-loaded micellar droplets, however, provided a significantly higher cellular uptake of the model drug FDA (2.2-fold, p ≤ 0.01) Conclusion: Due to undergoing a shift in zeta potential, the modified micelles significantly enhanced cellular uptake while preserving mucus-permeating properties.

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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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Mucus permeating self-emulsifying drug delivery systems (SEDDS): About the impact of mucolytic enzymes

Cited by 33 publications

References 26 publications

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

Self-emulsifying drug delivery system: Mucus permeation and innovative quantification technologies

Dual-Acting Zeta-Potential-Changing Micelles for Optimal Mucus Diffusion and Enhanced Cellular Uptake after Oral Delivery

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

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