Co-encapsulation of l-asparaginase and etoposide in dextran nanoparticles for synergistic effect in chronic myeloid leukemia cells

Konhäuser, Matthias; Kannaujiya, Vinod K.; Steiert, Elena; Schwickert, Kevin; Schirmeister, Tanja; Wich, Peter

doi:10.1016/j.ijpharm.2022.121796

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…The main reason for performing DEX acetylation is to allow solubility of DEX molecules in organic solvents, facilitating the encapsulation of various hydrophilic and hydrophobic active substances, which has always been challenging, and allowing their simultaneous delivery [ 62 ]. Ac-DEX is an essential derivative of DEX synthesized in mild conditions, at room temperature, from DEX and 2-methoxypropene in a one-step reaction catalysed by pyridinium p-toluene sulfonate [ 3 ].…”

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

“…Ac-DEX is an essential derivative of DEX synthesized in mild conditions, at room temperature, from DEX and 2-methoxypropene in a one-step reaction catalysed by pyridinium p-toluene sulfonate [ 3 ]. Ac-DEX contains cyclic and methoxy acyclic acetal moieties and has been shown to be biodegradable at neutral pH, biocompatible and pH-sensitive [ 4 , 62 ]. Because it is an acid-sensitive polymer, Ac-DEX degrades more rapidly at lower pH, for example in the endosome of phagocytic cells, tumours, or in areas with inflammation [ 63 ], making it an ideal carrier for a wide range of therapeutics.…”

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

“…It is suitable for vaccine applications, targeted host-directed therapies to macrophages, controlled release of drugs, chemotherapeutic delivery and engineered drug-delivery devices [ 64 ]. By the simultaneous release of different active substances, synergistic effects, as well as the reduction in side effects and solubility improvement could be achieved at lower concentrations and improved pharmacokinetics [ 62 ].…”

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

“…Pyraclostrobin, an antifungal agent, was successfully loaded in pH-sensitive Ac-DEX microparticles in order to treat Sclerotinia sclerotiorum plant infections [ 3 ]. Konhäuser et al (2022) [ 62 ] developed a DDS system in order to simultaneously release L-asparaginase and etoposide. The active substances have synergistic activity against chronic myeloid leukaemia (CML) K562 cells, but L-asparaginase is hydrophilic and etoposide is hydrophobic [ 62 ].…”

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

“…Konhäuser et al (2022) [ 62 ] developed a DDS system in order to simultaneously release L-asparaginase and etoposide. The active substances have synergistic activity against chronic myeloid leukaemia (CML) K562 cells, but L-asparaginase is hydrophilic and etoposide is hydrophobic [ 62 ]. This system has great potential for CML therapy due to its ingenious ability to release both compounds in a pH-dependent manner, leading to synergistic cytotoxicity, increased drug efficacy and reduced side effects [ 62 ].…”

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

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Dextran Formulations as Effective Delivery Systems of Therapeutic Agents

Petrovici¹,

Pinteala²,

Simiónescu

2023

Molecules

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Dextran is by far one of the most interesting non-toxic, bio-compatible macromolecules, an exopolysaccharide biosynthesized by lactic acid bacteria. It has been extensively used as a major component in many types of drug-delivery systems (DDS), which can be submitted to the next in-vivo testing stages, and may be proposed for clinical trials or pharmaceutical use approval. An important aspect to consider in order to maintain high DDS’ biocompatibility is the use of dextran obtained by fermentation processes and with a minimum chemical modification degree. By performing chemical modifications, artefacts can appear in the dextran spatial structure that can lead to decreased biocompatibility or even cytotoxicity. The present review aims to systematize DDS depending on the dextran type used and the biologically active compounds transported, in order to obtain desired therapeutic effects. So far, pure dextran and modified dextran such as acetalated, oxidised, carboxymethyl, diethylaminoethyl-dextran and dextran sulphate sodium, were used to develop several DDSs: microspheres, microparticles, nanoparticles, nanodroplets, liposomes, micelles and nanomicelles, hydrogels, films, nanowires, bio-conjugates, medical adhesives and others. The DDS are critically presented by structures, biocompatibility, drugs loaded and therapeutic points of view in order to highlight future therapeutic perspectives.

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Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

Section: Biomedical Applications Of Modified Dexmentioning

confidence: 99%

See 3 more Smart Citations

Dextran Formulations as Effective Delivery Systems of Therapeutic Agents

Petrovici¹,

Pinteala²,

Simiónescu

2023

Molecules

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CD133 ligand‐enhanced etoposide‐liposome complex for targeted killing of lung cancer cells

Nie,

Zhou,

Zheng

et al. 2024

Biotechnology Progress

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Lung cancer has a high incidence rate and a low cure rate, hence the urgent need for effective treatment methods. Current lung cancer drugs have several drawbacks, including low specificity, poor targeting, drug resistance, and irreversible damage to normal tissues. Therefore, there is a need to develop a safe and effective new drug that can target and kill tumor cells. In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand‐modified etoposide‐liposome complex (Lipo@ETP‐CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor‐killing effect. Our research results demonstrated that this nano‐drug had efficient targeting and tumor‐killing effects, indicating its potential for clinical application.

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Challenges of enzyme therapy: Why two players are better than one

Cuoghi,

Caraffi,

Anderlini

et al. 2024

WIREs Nanomed Nanobiotechnol

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Enzyme‐based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico‐chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off‐target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine‐based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug‐integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies

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Co-encapsulation of l-asparaginase and etoposide in dextran nanoparticles for synergistic effect in chronic myeloid leukemia cells

Cited by 15 publications

References 55 publications

Dextran Formulations as Effective Delivery Systems of Therapeutic Agents

Dextran Formulations as Effective Delivery Systems of Therapeutic Agents

CD133 ligand‐enhanced etoposide‐liposome complex for targeted killing of lung cancer cells

Challenges of enzyme therapy: Why two players are better than one

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