Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B

Serafim, Cláudia; Ferreira, Inês; Rijo, Patrícia; Pinheiro, Lídia; Faustino, Célia; Calado, António R. T.; García‐Río, Luis

doi:10.1016/j.ijpharm.2015.11.034

Cited by 23 publications

(19 citation statements)

References 81 publications

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“…Some cationic LAAs also show interesting biologic properties, such as in vitro antimicrobial and antibiofilm activities and promising anticancer activity (IC50 15.3-22.4 μmol L −1 ) in several human cancer cell lines [21][22][23]. 14 14 C 3 (C 16 His) 2 LAAs have also been studied as drug delivery agents for hydrophobic anticancer [24,25] and antimicrobial [26][27][28] drugs to enhance drug solubilization and bioavailability. LAAs improved the solubility of an investigational anticancer drug from <0.15 µg mL −1 to 8.62 mg mL −1 , being more efficient than nonionic polymeric surfactant polysorbate 80 being used as a model solubilizer, which only achieved 3.16 mg mL −1 drug solubilization [24].…”

Section: Structure and Characterizationmentioning

confidence: 99%

“…The micelles that were formed by a gemini LAA derived from cysteine, (C 8 Cys) 2 , under biomimetic conditions (phosphate buffered-saline (PBS), pH 7.4) were able to solubilize antifungal agent amphotericin B in its monomeric and less toxic form, which increased the molar solubilization ratio of the hydrophobic drug to 0.072 as compared to 0.036 in the commercial deoxycholate micellar formulation [26,27]. Cationic vesicles that formed by the lysine gemini LAA, C 6 (LL) 2 ( Figure 1) and cholesterol showed sustained and controlled release of methotrexate in vitro.…”

Section: -7n(gly)-12mentioning

confidence: 99%

“…This specificity usually differs in the preference of acyl and alkyl group size. Some lipases show a strong or a weak stereospecificity, examples are, respectively, Rizhomucor miehei lipase (RML) and porcine pancreatic lipase (PPL) [27]. The specificity of lipases is categorized by the position of ester bonds (hydrolysed or formed) in the substrate molecules (regioselectivity), the class of substrate accepted (chemo-selectivity), and stereoselectivity [44].…”

Section: Hydrolysismentioning

confidence: 99%

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Lipoaminoacids Enzyme-Based Production and Application as Gene Delivery Vectors

et al. 2019

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Biosurfactant compounds have been studied in many applications, including biomedical, food, cosmetic, agriculture, and bioremediation areas, mainly due to their low toxicity, high biodegradability, and multifunctionality. Among biosurfactants, the lipoplexes of lipoaminoacids play a key role in medical and pharmaceutical fields. Lipoaminoacids (LAAs) are amino acid-based surfactants that are obtained from the condensation reaction of natural origin amino acids with fatty acids or fatty acid derivatives. LAA can be produced by biocatalysis as an alternative to chemical synthesis and thus become very attractive from both the biomedical and the environmental perspectives. Gemini LAAs, which are made of two hydrophobic chains and two amino acid head groups per molecule and linked by a spacer at the level of the amino acid residues, are promising candidates as both drug and gene delivery and protein disassembly agents. Gemini LAA usually show lower critical micelle concentration, interact more efficiently with proteins, and are better solubilising agents for hydrophobic drugs when compared to their monomeric counterparts due to their dimeric structure. A clinically relevant human gene therapy vector must overcome or avoid detect and silence foreign or misplaced DNA whilst delivering sustained levels of therapeutic gene product. Many non-viral DNA vectors trigger these defence mechanisms, being subsequently destroyed or rendered silent. The development of safe and persistently expressing DNA vectors is a crucial prerequisite for a successful clinical application, and it one of the main strategic tasks of non-viral gene therapy research.

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Section: Structure and Characterizationmentioning

confidence: 99%

Section: -7n(gly)-12mentioning

confidence: 99%

Section: Hydrolysismentioning

confidence: 99%

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Lipoaminoacids Enzyme-Based Production and Application as Gene Delivery Vectors

et al. 2019

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“…The polar headgroup of LAA, which contains both donor and acceptor hydrogen bonding groups capable of intra‐ and intermolecular interactions, adds further complexity to their self‐assembly behavior. LAA have been employed as drug delivery agents for hydrophobic drugs (Ménard et al, ; Serafim et al, ), enhancing drug solubilization and bioavailability. Moreover, LAA are obtained from naturally renewable sources and can be produced by green‐chemistry approaches that include biotechnological procedures, such as fermentation or enzymatic catalysis (Ménard et al, ; Pérez et al, ; Pinazo et al, ; Serafim et al, ).…”

Section: Introductionmentioning

confidence: 99%

Self‐Assembly of Lipoaminoacids‐DNA Based on Thermodynamic and Aggregation Properties

Faustino

Martins

Duarte

et al. 2020

J Surfact & Detergents

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Lipoamino acids (LAA) are biocompatible and biodegradable biosurfactants, a promising alternative to viral vectors in gene delivery. LAA are constituted by a polar head, the amino acid, and a hydrocarbon (alkyl) chain usually from a fatty acid or fatty acid derivative, such as a fatty amine or a fatty alcohol. In this work, dodecyl LAA was produced from dodecylamine and natural L-amino acids cystine (Cys), lysine (Lys), and phenylalanine (Phe) using an enzyme-based approach with porcine pancreatic lipase. The self-assembly behavior of LAA solutions, in the absence or presence of DNA, was studied by conductivity and fluorescence regarding the application as transfection agents. Conductivity measurements yielded important system parameters, including critical micelle concentration (CMC) and standard Gibbs energy of micellization (ΔG mic ) for pure LAA systems, and apparent critical aggregation concentration (CAC app ) and apparent standard Gibbs energy of aggregation (ΔG agg ) for the mixed LAA-DNA systems. The CMC increased in the order of decreasing lipophilicity: (C 12 Cys) 2 < C 12 Phe < C 12 Lys, CMC values were higher in the presence of DNA, suggesting the formation of a LAA-DNA complex responsible for hindering the micellization process. Binding of the LAA with DNA was confirmed from fluorescence measurements for the ethidium bromide exclusion assay. Results suggest a weak interaction of the LAA with DNA which can be attributed to their relatively short dodecyl chains and/or the ionic strength of the buffer solution, supporting the role of hydrophobic interactions in complex formation between DNA and the oppositely charged surfactant in combination with electrostatic interactions. The CAC app values decreased with increasing LAA hydrophobicity, reflecting the relevance of hydrophobic interactions in complex coacervation.

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“…19 Studies have reported that the combined use of bile salts with compounds, such as phospholipids, fatty acids, and polyamines, may improve their effectiveness as absorption enhancers and allow a decrease in their concentrations, thus reducing the risks of membrane dissolution. 20,21 Researchers have reported that the conjugation of cholic acid to anticancer drugs, such as carboplatin and cisplatin, resulted in significant antitumor efficiency in platinum-resistant tumor models. 18,22 The organotropism of bile acids can also help overcome chemotherapy resistance of enterohepatic tumors and reduce noxious side effects to healthy tissue by selectively targeting drugs to tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

Zhang¹,

Wu²,

Zhang³

et al. 2017

IJN

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Purpose Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)- block -poly ( d , l -lactide) (mPEG-PDLLA). Methods PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated. Results The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC 0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications. Conclusion These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

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Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B

Cited by 23 publications

References 81 publications

Lipoaminoacids Enzyme-Based Production and Application as Gene Delivery Vectors

Lipoaminoacids Enzyme-Based Production and Application as Gene Delivery Vectors

Self‐Assembly of Lipoaminoacids‐DNA Based on Thermodynamic and Aggregation Properties

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

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