Advances in the therapeutic delivery and applications of functionalized Pluronics: A critical review

Singla, Pankaj; Garg, Saweta; McClements, Jake; Jamieson, Oliver; Peeters, Marloes; Mahajan, Rakesh Kumar

doi:10.1016/j.cis.2021.102563

Cited by 58 publications

(35 citation statements)

References 289 publications

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Section: Introductionmentioning

confidence: 99%

“…This makes Poloxamers particularly well‐suited as scaffolds for creating polymer‐linked prodrugs designed to enhance drug delivery to solid tumors. However, while used extensively in their chemically unmodified form, 21,24 their utility for making prodrug‐based delivery systems to improve cancer pharmacotherapy has remained largely unexplored 28 …”

Section: Introductionmentioning

confidence: 99%

“…However, while used extensively in their chemically unmodified form, 21,24 their utility for making prodrug-based delivery systems to improve cancer pharmacotherapy has remained largely unexplored. 28 of high-risk neuroblastoma, PF108-[SN22] 2 can pave the way to a robust and clinically viable therapeutic strategy urgently needed for patients with multidrugresistant disease presently lacking effective treatment options.…”

Section: Introductionmentioning

confidence: 99%

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Poloxamer‐linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high‐risk neuroblastoma with primary and acquired chemoresistance

et al. 2022

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High‐risk solid tumors continue to pose a tremendous therapeutic challenge due to multidrug resistance. Biological mechanisms driving chemoresistance in high‐risk primary and recurrent disease are distinct: in newly diagnosed patients, non‐response to therapy is often associated with a higher level of tumor “stemness” paralleled by overexpression of the ABCG2 drug efflux pump, whereas in tumors relapsing after non‐curative therapy, poor drug sensitivity is most commonly linked to the dysfunction of the tumor suppressor protein, p53. In this study, we used preclinical models of aggressive neuroblastoma featuring these characteristic mechanisms of primary and acquired drug resistance to experimentally evaluate a macromolecular prodrug of a structurally enhanced camptothecin analog, SN22, resisting ABCG2‐mediated export, and glucuronidation. Together with extended tumor exposure to therapeutically effective drug levels via reversible conjugation to Pluronic F‐108 (PF108), these features translated into rapid tumor regression and long‐term survival in models of both ABCG2‐overexpressing and p53‐mutant high‐risk neuroblastomas, in contrast to a marginal effect of the clinically used camptothecin derivative, irinotecan. Our results demonstrate that pharmacophore enhancement, increased tumor uptake, and optimally stable carrier‐drug association integrated into the design of the hydrolytically activatable PF108‐[SN22]2 have the potential to effectively combat multiple mechanisms governing chemoresistance in newly diagnosed (chemo‐naïve) and recurrent forms of aggressive malignancies. As a macromolecular carrier‐based delivery system exhibiting remarkable efficacy against two particularly challenging forms of high‐risk neuroblastoma, PF108‐[SN22]2 can pave the way to a robust and clinically viable therapeutic strategy urgently needed for patients with multidrug‐resistant disease presently lacking effective treatment options.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Poloxamer‐linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high‐risk neuroblastoma with primary and acquired chemoresistance

et al. 2022

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“…Pluronics have found numerous applications in the pharmaceutical industry due to their non-ionic, amphiphilic, and non-toxic nature; ability to form micelles; thermoresponsive gelling properties; and excellent biocompatibility and biodegradability [ 30 , 31 ]. They are commonly used in drug solubilisation, gene/therapeutic delivery, diagnostics, and tissue engineering applications.…”

Section: Introductionmentioning

confidence: 99%

“…They are commonly used in drug solubilisation, gene/therapeutic delivery, diagnostics, and tissue engineering applications. Their properties and various applications in pharmaceutical formulations and drug delivery are comprehensively discussed in a number of recently published reviews [ 31 , 32 , 33 , 34 , 35 , 36 ]. Pluronics are also commonly used in the preparation of solid dispersions (SDs) to improve the dissolution rate of poorly soluble drugs.…”

Section: Introductionmentioning

confidence: 99%

Melting Point Depression of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Polymers in Supercritical Carbon Dioxide in the Presence of Menthol as a Solid Co-Plasticiser

et al. 2022

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The melting behaviour of the triblock polymers, Pluronic F38, F68, F77, F108, and F127, was investigated in pressurised CO2 and in the presence of menthol. The melting points of the polymers combined with 0, 10, 25, and 50 wt% of menthol were studied at atmospheric pressure and compared with those at 10 and 20 MPa in supercritical carbon dioxide (scCO2). The highest melting point depressions of 16.8 ± 0.5 °C and 29.0 ± 0.3 °C were observed at 10 and 20 MPa, respectively. The melting point of triblock polymers in pressurised CO2 was found to be dependent on molecular weight, poly(propylene oxide) (PPO) content, and menthol percentage. The melting point of most of the polymers studied in this work can be reduced to room temperature, which can be pivotal to the formulation development of thermolabile substances using these polymers.

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Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles

Peng,

Hu,

Zhang

et al. 2024

Adv Healthcare Materials

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Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near‐infrared (NIR)‐absorbing and heavy‐atom‐free Aza‐BODIPY dye is presented that exhibits both type‐I and type‐II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F‐127), yielding BDP‐6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor‐associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much‐desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.

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Advances in the therapeutic delivery and applications of functionalized Pluronics: A critical review

Cited by 58 publications

References 289 publications

Poloxamer‐linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high‐risk neuroblastoma with primary and acquired chemoresistance

Poloxamer‐linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high‐risk neuroblastoma with primary and acquired chemoresistance

Melting Point Depression of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Polymers in Supercritical Carbon Dioxide in the Presence of Menthol as a Solid Co-Plasticiser

Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles

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