Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring

Kurpiers, Markus; Wolf, Julian Dominik; Spleis, Helen; Steinbring, Christian; Jörgensen, Arne Matteo; Matuszczak, Barbara; Bernkop‐Schnürch, Andreas

doi:10.1016/j.xphs.2020.07.024

Cited by 13 publications

(17 citation statements)

References 34 publications

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“…Meanwhile, the logP oct/water value of insulin can be estimated from the solubility values in water and n-octanol under the standard conditions to be around −2.4 [ 64 ]. The hydrophilicity of insulin, in fact, presents a major problem for its delivery across the intestinal epithelial barrier, for which reason it is often combined with various carriers that impart a degree of hydrophobicity to it [ 65 ], thus increasing its transportability via the oral delivery route. If insulin is incorporated into the PCL carrier in one such hydrophobic form, then the model implemented here would be a more veritable reflection of its release characteristics than it is for pure insulin.…”

Section: Discussionmentioning

confidence: 99%

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Uskoković

2023

Materials

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Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes.

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Section: Discussionmentioning

confidence: 99%

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Uskoković

2023

Materials

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“…Amino acid-based surfactants, which can be degraded by enzymes into non-toxic fragments, are attracting more and more attention [51][52][53][54]. For example, arginine-based surfactants demonstrate a good antimicrobial activity, biodegradability, and low toxicity [55].…”

Section: Amino Acid Surfactantsmentioning

confidence: 99%

“…Nanocontainers based on amino acid surfactants can be used as carriers for a wide range of medicines [22,34,[41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Lysine-based surfactants were obtained to improve the solubilization of water insoluble anticancer drugs [59].…”

Section: Amino Acid Surfactantsmentioning

confidence: 99%

“…This promotes the inclusion of drug molecules in surfactant-based nanocontainers, which can improve their oral bioavailability [63,64]. In [51], the degradation of lysine-based surfactants was studied. Enzymatic cleavage of cholesterol lysinate (CL), oleyl lysinate (OL) and decyl lysinate (DL) was investigated by incubating lysine esters with isolated enzymes.…”

Section: Amino Acid Surfactantsmentioning

confidence: 99%

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Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

et al. 2021

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This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.

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“…In this sense, new amphiphilic substances, besides the lauric acid, with higher biodegradability should be investigated to obtain SUPRAs with low environmental impact [79,80] in order to make even more versatile the SSME and, moreover, it is mandatory to reduce the organic solvent (i.e., THF) needed for the coacervation step.…”

Section: Conclusion and Future Trendsmentioning

confidence: 99%

Use of green alternative solvents in dispersive liquid‐liquid microextraction: A review

Grau

Azorín

Benedé

et al. 2021

J of Separation Science

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Dispersive liquid-liquid microextraction is one of the most widely used microextraction techniques currently in the Analytical Chemistry field, mainly due to its simplicity and rapidity. The operational mode of this approach has been constantly changing since its introduction, adapting to new trends and applications.Most of these changes are related to the nature of the solvent employed for the microextraction. From the classical halogenated solvents (e.g., chloroform or dichloromethane), different alternatives have been proposed in order to obtain safer and non-pollutants microextraction applications. In this sense, low density solvents, such as alkanols, switchable hydrophobicity solvents and ionic liquids were the first and most popular replacements for halogenated solvents, which provided similar or better results than these classical dispersive liquid-liquid microextraction solvents.However, despite the good performances obtained with low density solvents and

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Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring

Cited by 13 publications

References 34 publications

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

Use of green alternative solvents in dispersive liquid‐liquid microextraction: A review

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