Amphiphilically-modified gelatin nanoparticles: Self-assembly behavior, controlled biodegradability, and rapid cellular uptake for intracellular drug delivery

The design of efficient drug-delivery vehicles remains a big challenge in materials science. Herein, we describe a novel class of amphiphilic hybrid dendrimers that consist of a poly(amidoamine) (PAMAM) dendritic core functionalized with bisMPA dendrons bearing cholesterol and coumarin moieties. Their self-assembly behavior both in bulk and in water was investigated. All dendrimers exhibited smectic A or hexagonal columnar liquid crystal organizations, depending on the generation of the dendrimer. In water, these dendrimers self-assembled to form stable spherical micelles that could encapsulate Nile Red, a hydrophobic model compound. The cell viability in vitro of the micelles was studied in HeLa cell line, and proved to be non-toxic up to 72 h of incubation. Therefore, these spherical micelles allow the encapsulation of hydrophobic molecules, and at the same time provided fluorescent traceability due to the presence of coumarin units in their chemical structure, demonstrating the potential of these dendrimers as nanocarriers for drug-delivery applications.

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Drug-induced hierarchical self-assembly of poly(amino acid) for efficient intracellular drug delivery

Chinese Chemical Letters ◽

10.1016/j.cclet.2020.10.016 ◽

2020 ◽

Author(s):

Zifen Li ◽

Yanxue Yang ◽

Chuan Peng ◽

Hang Liu ◽

Rui Yang ◽

...

Keyword(s):

Drug Delivery ◽

Amino Acid ◽

Self Assembly ◽

Drug Induced ◽

Intracellular Drug Delivery

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Review of Contemporary Self-Assembled Systems for the Controlled Delivery of Therapeutics in Medicine

Nanomaterials ◽

10.3390/nano11020278 ◽

2021 ◽

Vol 11 (2) ◽

pp. 278

Author(s):

Laura Osorno ◽

Alyssa Brandley ◽

Daniel Maldonado ◽

Alex Yiantsos ◽

Robert Mosley ◽

...

Keyword(s):

Drug Delivery ◽

Self Assembly ◽

Deep Understanding ◽

Drug Bioavailability ◽

Medical Needs ◽

Self Assembling ◽

Amphiphilic Molecules ◽

Self Assembled ◽

Assembly Behavior ◽

External Stimuli

The novel and unique design of self-assembled micro and nanostructures can be tailored and controlled through the deep understanding of the self-assembly behavior of amphiphilic molecules. The most commonly known amphiphilic molecules are surfactants, phospholipids, and block copolymers. These molecules present a dual attraction in aqueous solutions that lead to the formation of structures like micelles, hydrogels, and liposomes. These structures can respond to external stimuli and can be further modified making them ideal for specific, targeted medical needs and localized drug delivery treatments. Biodegradability, biocompatibility, drug protection, drug bioavailability, and improved patient compliance are among the most important benefits of these self-assembled structures for drug delivery purposes. Furthermore, there are numerous FDA-approved biomaterials with self-assembling properties that can help shorten the approval pathway of efficient platforms, allowing them to reach the therapeutic market faster. This review focuses on providing a thorough description of the current use of self-assembled micelles, hydrogels, and vesicles (polymersomes/liposomes) for the extended and controlled release of therapeutics, with relevant medical applications. FDA-approved polymers, as well as clinically and commercially available nanoplatforms, are described throughout the paper.

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The Molecular Structure and Self-Assembly Behavior of Reductive Amination of Oxidized Alginate Derivative for Hydrophobic Drug Delivery

Molecules ◽

10.3390/molecules26195821 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5821

Author(s):

Xiuqiong Chen ◽

Qingmei Zhu ◽

Zhengyue Li ◽

Huiqiong Yan ◽

Qiang Lin

Keyword(s):

Molecular Structure ◽

Drug Delivery ◽

Self Assembly ◽

Reductive Amination ◽

Critical Aggregation Concentration ◽

Gravimetric Analysis ◽

Hydrophobic Drug ◽

Amination Reaction ◽

Raw264.7 Cell ◽

Assembly Behavior

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a 1H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about −69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.

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Fabrication of Carboxylmethyl Chitosan Nanocarrier via Self-Assembly for Efficient Delivery of Phenylethyl Resorcinol in B16 Cells

Polymers ◽

10.3390/polym12020408 ◽

2020 ◽

Vol 12 (2) ◽

pp. 408 ◽

Cited By ~ 2

Author(s):

Pei Zhang ◽

Huixia Guo ◽

Chenguang Liu

Keyword(s):

Drug Delivery ◽

Cellular Uptake ◽

Self Assembly ◽

Chemical Properties ◽

The Body ◽

Efficient Delivery ◽

Mean Size ◽

Physical And Chemical ◽

Drug Nanocarriers ◽

And Chemical Properties

Micro-molecular drugs have special advantages to cope with challenging diseases, however their structure, physical and chemical properties, stability, and pharmacodynamics have more requirements for the way they are delivered into the body. Carrier-based drug delivery systems can circumvent many limited factors of drug delivery and increase their bioavailability. In this context, stable drug nanocarriers of alkaline amino acids (arginine, Arg) modified conjugated linoleic acid-carboxymethyl chitosan (CLA-CMCS) conjugate were developed, which could generate supramolecular micelles to effectively encapsulate the tyrosinase inhibitor phenylethyl resorcinol (PR). The resulting CCA-NPs were spherical nanoparticles with a mean size around 175 nm. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cellular uptake investigation demonstrated that the CCA-NPs were non-cytotoxic and had excellent cell transport ability. In addition, these CCA-NPs were able to effectively deliver PR and inhibited melanin formation to reduce pigmentation by enhancing cellular uptake. In conclusion, our research indicated that nanocarriers based on self-assembly amphiphilic polymers constituted a promising and effective drug delivery system in hyperpigmentation targeting.

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Self-Assembly of Amphiphilic Compounds as a Versatile Tool for Construction of Nanoscale Drug Carriers

International Journal of Molecular Sciences ◽

10.3390/ijms21186961 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6961

Author(s):

Ruslan Kashapov ◽

Gulnara Gaynanova ◽

Dinar Gabdrakhmanov ◽

Denis Kuznetsov ◽

Rais Pavlov ◽

...

Keyword(s):

Drug Delivery ◽

Self Assembly ◽

Lipid Membrane ◽

Synergetic Effect ◽

Drug Carriers ◽

Biological Species ◽

Endosomal Escape ◽

Macrocyclic Compounds ◽

Intracellular Drug Delivery ◽

Lipid Formulations

This review focuses on synthetic and natural amphiphilic systems prepared from straight-chain and macrocyclic compounds capable of self-assembly with the formation of nanoscale aggregates of different morphology and their application as drug carriers. Since numerous biological species (lipid membrane, bacterial cell wall, mucous membrane, corneal epithelium, biopolymers, e.g., proteins, nucleic acids) bear negatively charged fragments, much attention is paid to cationic carriers providing high affinity for encapsulated drugs to targeted cells. First part of the review is devoted to self-assembling and functional properties of surfactant systems, with special attention focusing on cationic amphiphiles, including those bearing natural or cleavable fragments. Further, lipid formulations, especially liposomes, are discussed in terms of their fabrication and application for intracellular drug delivery. This section highlights several features of these carriers, including noncovalent modification of lipid formulations by cationic surfactants, pH-responsive properties, endosomal escape, etc. Third part of the review deals with nanocarriers based on macrocyclic compounds, with such important characteristics as mucoadhesive properties emphasized. In this section, different combinations of cyclodextrin platform conjugated with polymers is considered as drug delivery systems with synergetic effect that improves solubility, targeting and biocompatibility of formulations.

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