Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin

Palmiero, Umberto Capasso; Morosi, Lavinia; Bello, Ezia; Ponzo, Marianna; Frapolli, Roberta; Matteo, Cristina; Ferrari, Mariella; Zucchetti, Massimo; Minoli, Lucia; Maglie, Marcella De; Romanelli, Pierpaolo; Morbidelli, Massimo; D’Incalci, Maurizio; Moscatelli, Davide

doi:10.1016/j.jconrel.2018.03.005

Cited by 13 publications

(5 citation statements)

References 38 publications

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“…Biodegradable polymer nanoparticles (NPs) are rapidly coming to the forefront of drug delivery, diagnosis, and other areas of biomedicine due to their versatility and the ability to degrade under physiological conditions. − In particular, they have been successfully used to formulate poorly water-soluble drugs avoiding the use of toxic surfactants, such as the cremophor EL in the case of the novel NP-based paclitaxel formulations (e.g., Genexol), or to reduce the side-effects of many drugs (e.g., Doxil and Trabectedin).…”

Section: Introductionmentioning

confidence: 99%

“…Among the many types of NPs developed, the ones structurally composed of a polyester core and a polyethylene glycol (PEG) shell are the most studied and adopted so far. , In fact, the polyester chains provide a suitable environment for the encapsulation of hydrophobic drugs and confer biodegradability to the NPs, being amenable to hydrolysis. On the other hand, the PEG portion confers colloidal stability and, at the same time, allows the NPs to escape the body immune system and the nonspecific absorption of proteins .…”

Section: Introductionmentioning

confidence: 99%

“…To overcome this technological complication, we have recently developed a method to formulate drugs into NPs directly at the point of care just by using a common syringe. ,, This method consists in the dissolution of an amphiphilic copolymer and the drug in a small amount of a slightly toxic water-miscible solvent (e.g., DMSO or ethanol). This organic mixture then undergoes few aspiration/ejection cycles through the needle of a syringe preloaded with an isotonic solution (e.g., phosphate-buffered saline, PBS).…”

Section: Introductionmentioning

confidence: 99%

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Preformed Biodegradable Zwitterionic Nanoparticles as Tunable Excipients for the Formulation of Therapeutics Directly at the Point of Care

Auriemma

Sponchioni

Lotti

et al. 2021

Ind. Eng. Chem. Res.

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Polyester-based nanoparticles (NPs) are among the most adopted drug delivery systems developed so far. This is mainly due to their ability to increase the bioavailability of the loaded therapeutics, to prevent the adverse effects often associated with their use, and to eliminate the toxic excipients necessary to formulate them. In addition, these NPs are biodegradable under physiological conditions thus avoiding the polymer accumulation in the body. However, the complexity in the formulation and storage hampers the cost-effective use of these formulations reducing their availability among the patient population. In addition, the manifold drugs available on the market, characterized by different chemical structures and charges, impose the continuous optimization of different delivery systems for their efficient formulation. Therefore, tunable NPs able to encapsulate different drugs with high loading efficiencies and to modulate their release after administration are urgently needed. In this work, a method to formulate different drugs directly at the point of care using only a syringe and starting from preformed NPs has been developed. Highly tunable zwitterionic NPs have been synthesized via the combination of ring opening polymerization and reversible addition–fragmentation chain transfer emulsion polymerization and then used to load paclitaxel, doxorubicin, or ibuprofen with high efficiency. The controlled release of such therapeutics has been achieved by tuning the characteristics of the NPs, in particular by the addition of charged groups.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preformed Biodegradable Zwitterionic Nanoparticles as Tunable Excipients for the Formulation of Therapeutics Directly at the Point of Care

Auriemma

Sponchioni

Lotti

et al. 2021

Ind. Eng. Chem. Res.

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“…The black color observed in the magnetite aqueous suspension was preserved after the polymer addition and the nanoprecipitation process. This nanoprecipitation method is well established for synthesizing organic nanoparticles by hydrophobic interactions of amphiphilic polymers, allowing the encapsulation of hydrophobic molecules. Nevertheless, it was still not reported for the formation of polymer–inorganic nanocomposites.…”

Section: Resultsmentioning

confidence: 99%

Magnetite Nanoparticles Coated with Biodegradable Zwitterionic Polymers as Multifunctional Nanocomposites for Drug Delivery and Cancer Treatment

Perecin

Sponchioni

Auriemma

et al. 2022

ACS Appl. Nano Mater.

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Tailor-made materials for biomedical applications can be constructed with different building blocks to confer multiple functions on one platform. Here, we demonstrate the facile synthesis of magnetite-biodegradable polymer nanocomposites combining superparamagnetism with the possibility of loading and controlling the release of a lipophilic drug. The magnetite nanoparticles were synthesized by reduction–precipitation and used as nuclei to grow a biodegradable zwitterionic shell. The copolymer used for this scope comprises a hydrophobic block made of a biodegradable ε-caprolactone-based macromonomer (CL n ) with three different degrees of polymerization (DP n , n = 3, 5, and 7) obtained by ring-opening polymerization (ROP). Dopamine molecules were attached to the end of this CL n oligomer (CL n Dopa), conferring a specific affinity for the magnetite surface. A hydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) block (PMPC) was included by reversible addition–fragmentation chain transfer (RAFT) polymerization to add colloidal stability and water dispersibility to the copolymer. This PMPC was chain-extended with CL n Dopa via RAFT polymerization targeting four different DP m (m = 10, 20, 30, and 40), resulting in a library of 12 copolymers. A facile nanoprecipitation process produced copolymer nanoparticles and copolymer-coated magnetite nanostructures. Physicochemical characterization confirmed the inorganic–organic composite nature. The copolymer-coated magnetic materials showed water stability, superparamagnetic behavior, and appropriate hyperthermic ability under an alternate magnetic field. Biological assays using HeLa cells showed high biocompatibility and efficient nanoparticle uptake. In addition, a sustained release of dexamethasone, used as a model drug encapsulated in the polymer shell, and local heating as a dual functional material could be accessed.

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“…Interestingly, it has been proposed that these Ecteinascidins may be combined with specific antibodies forming antibody-drug complexes (ADC) [ 165 ] and nanoparticles [ 168 ]. These approaches might help to overcome unwanted collateral side effects and improve safety parameters, both locally in the vasculature at the injection site, and systemically.…”

Section: Combination Therapies Involving Trabectedin and Lurbinectedinmentioning

confidence: 99%

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment—Progresses in Their Use in Combined Cancer Therapy

Povo-Retana,

Landauro-Vera,

Alvarez-Lucena

et al. 2024

Molecules

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Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-β-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

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Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin

Cited by 13 publications

References 38 publications

Preformed Biodegradable Zwitterionic Nanoparticles as Tunable Excipients for the Formulation of Therapeutics Directly at the Point of Care

Preformed Biodegradable Zwitterionic Nanoparticles as Tunable Excipients for the Formulation of Therapeutics Directly at the Point of Care

Magnetite Nanoparticles Coated with Biodegradable Zwitterionic Polymers as Multifunctional Nanocomposites for Drug Delivery and Cancer Treatment

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment—Progresses in Their Use in Combined Cancer Therapy

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