Crosslinked casein-based micelles as a dually responsive drug delivery system

Picchio, Matías L.; Cuggino, Julio César; Nagel, Gregor; Wedepohl, Stefanie; Minari, Roque Javier; Igarzabal, Cecilia Inés Álvarez; Gugliotta, Luis Marcelino; Calderón, Marcelo

doi:10.1039/c8py00600h

Cited by 44 publications

(30 citation statements)

References 44 publications

(46 reference statements)

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“…Blank NaCNs on the other hand, demonstrated excellent biocompatibility [ 24 ] with more than 75% cell viability ( Figure 13 ) in almost all concentrations of sodium caseinate used to prepare NaCNs [ 69 ].…”

Section: Resultsmentioning

confidence: 99%

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells

et al. 2020

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Background: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release. Methods: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines. Results: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and −20 °C and when placed at a temperature of 37 °C. Conclusions: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.

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Section: Resultsmentioning

confidence: 99%

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells

et al. 2020

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“…Recently, casein micelles linked using glyceraldehyde and loaded with hydrophobic molecules have been tested as drug delivery vehicles in vitro. 147 These casein NPs showed a controlled degradation under simulated intra-lysosomal conditions; once suspended in neutral (pH = 7.4) or acidic buffer (pH = 5) casein micelles underwent to mild or significant degradation, respectively. Furthermore, their structure was completely destroyed in presence of proteases like trypsin.…”

Section: Milk Proteins Casein Micelles and Fat Globulesmentioning

confidence: 95%

“…146 However, due to change of the fluid phase, after systemic administration casein NPs often disassemble. 147 Several techniques have been used to build more stable crosslinked casein micelles. Recently, casein micelles linked using glyceraldehyde and loaded with hydrophobic molecules have been tested as drug delivery vehicles in vitro.…”

Section: Milk Proteins Casein Micelles and Fat Globulesmentioning

confidence: 99%

“…Furthermore, their structure was completely destroyed in presence of proteases like trypsin. 147 Conclusively, stable crosslinked casein micelles could survive to blood circulation conditions but can be completely disassembled by lysosomal conditions with a consequent time-dependent release of their cargo. This make them suitable carriers for intracellular delivery of hydrophobic molecules, such as anticancer therapeutics.…”

Section: Milk Proteins Casein Micelles and Fat Globulesmentioning

confidence: 99%

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The nanostructured secretome

et al. 2020

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“…A very interesting study was carried out by Picchio et al [ 156 ], who prepared casein micelles crosslinked with glyceraldehyde (GAL) and loaded with Nile red as a model hydrophobic drug. As a function of the dialysis time, the micellar sizes increased from 128 to 509 nm.…”

Section: Micellar Drug Delivery Systems Based On Proteinsmentioning

confidence: 99%

Micellar Drug Delivery Systems Based on Natural Biopolymers

Atanase

2021

Polymers

128

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The broad diversity of structures and the presence of numerous functional groups available for chemical modifications represent an enormous advantage for the development of safe, non-toxic, and cost-effective micellar drug delivery systems (DDS) based on natural biopolymers, such as polysaccharides, proteins, and peptides. Different drug-loading methods are used for the preparation of these micellar systems, but it appeared that dialysis is generally recommended, as it avoids the formation of large micellar aggregates. Moreover, the preparation method has an important influence on micellar size, morphology, and drug loading efficiency. The small size allows the passive accumulation of these micellar systems via the permeability and retention effect. Natural biopolymer-based micellar DDS are high-value biomaterials characterized by good compatibility, biodegradability, long blood circulation time, non-toxicity, non-immunogenicity, and high drug loading, and they are biodegraded to non-toxic products that are easily assimilated by the human body. Even if some recent studies reported better antitumoral effects for the micellar DDS based on polysaccharides than for commercial formulations, their clinical use is not yet generalized. This review is focused on the studies from the last decade concerning the preparation as well as the colloidal and biological characterization of micellar DDS based on natural biopolymers.

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Crosslinked casein-based micelles as a dually responsive drug delivery system

Abstract: Crosslinked casein micelles with a dual pH and protease drug triggered release can be applied as a promising hydrophobic drug carrier material.

Cited by 44 publications

References 44 publications

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells

Optimization and Formulation of Nanostructured and Self-Assembled Caseinate Micelles for Enhanced Cytotoxic Effects of Paclitaxel on Breast Cancer Cells

The nanostructured secretome

Micellar Drug Delivery Systems Based on Natural Biopolymers

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