Liposomal Carrier Conjugated to APP-Derived Peptide for Brain Cancer Treatment

Gabay, Martín; Weizman, Abraham; Zeineh, Nidal; Kahana, Meygal; Obeid, Fadi; Allon, Nahum; Gavish, Moshe

doi:10.1007/s10571-020-00969-1

Cited by 26 publications

(33 citation statements)

References 28 publications

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“…Curcumin liposomes were also shown to inhibit tumor growth and increase the survival period of brain glioma-bearing mice [ 161 ]. Other than that, a study showed that curcumin-loaded targeted liposomes cross the BBB two-fold higher than the non-targeted liposomes loaded with curcumin [ 162 ]. Curcumin-loaded targeted liposomes can more effectively inhibit GBM tumor growth and increase the survival rate of U87 GBM tumor-bearing mice compared to free curcumin as well as the non-targeted liposome-loaded curcumin [ 162 ].…”

Section: Issues Of Curcumin Bioavailability and Methods To Overcommentioning

confidence: 99%

“…Other than that, a study showed that curcumin-loaded targeted liposomes cross the BBB two-fold higher than the non-targeted liposomes loaded with curcumin [ 162 ]. Curcumin-loaded targeted liposomes can more effectively inhibit GBM tumor growth and increase the survival rate of U87 GBM tumor-bearing mice compared to free curcumin as well as the non-targeted liposome-loaded curcumin [ 162 ]. Additionally, curcumin phytosome meriva (CCP) has been shown to improve curcumin bioavailability [ 163 ], which then help to activate natural killer cells and mediate elimination of GBM and GBM stem cells [ 164 ].…”

Section: Issues Of Curcumin Bioavailability and Methods To Overcommentioning

confidence: 99%

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Anticancer Mechanism of Curcumin on Human Glioblastoma

2021

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Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.

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Section: Issues Of Curcumin Bioavailability and Methods To Overcommentioning

confidence: 99%

Section: Issues Of Curcumin Bioavailability and Methods To Overcommentioning

confidence: 99%

Anticancer Mechanism of Curcumin on Human Glioblastoma

2021

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“…Another study focused on the development of targeted liposomes for brain cancer treatment was published by Gabay et al [82]. The proposed system was composed of PC-based liposomes functionalized with a targeting peptide made of a short sequence of 5 amino acids (RERMS) present in the amyloid precursor protein (APP), which can effectively cross the BBB.…”

Section: Targeting Liposomesmentioning

confidence: 99%

“…In addition, only recently has it been demonstrated that TMZ's partition is dependent on liposome lipid composition and pH [113]. For this reason, reports of TMZ-loaded liposomes generated through thin-film hydration use TMZ dissolved either in the lipid [51,55,82] or in the aqueous phase [52,80]. The reported TMZ-encapsulating MLVs are generally extruded for obtaining a more homogenous population of SUVs, although unextruded LUVs formed by hydrating sieved dry lipid films (proliposomes) have also been reported [9,114], as well as SUVs obtained through sonication of hydrated lyophilized lipid cakes [52].…”

Section: Thin-film Hydration (Thf)mentioning

confidence: 99%

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

et al. 2022

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Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market.

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“…Specifically, liposomal drug delivery is a promising strategy, as many liposome encapsulated drugs are currently undergoing clinical trials [15][16][17]. Liposomes act as an effective vehicle to bring active compounds to their target site, therefore increasing drug bioavailability [18,19]. This allows liposomes to decrease the dosage required to achieve a therapeutic effect and therefore improve the safety profile of these drugs.…”

Section: Introductionmentioning

confidence: 99%

Resurrecting the Dead: Mitigating Efflux-Pump Inhibitor Toxicity using a Liposomal Delivery System to Recover Efficacy of Antimicrobial Drugs

Ray

Nguyen

et al. 2021

URNCST Journal

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Introduction: Antimicrobial resistance (AMR) has become concerningly prevalent on a global scale as many infectious agents have evolved to evade antimicrobials effects, making it difficult to treat infectious diseases. Pseudomonas aeruginosa is a multiresistant bacteria that requires urgent attention as it is detrimental in lung infections. Activity of membraneembedded efflux pumps, such as the MexAB-OprM pump, is a principal mechanism by which bacterial species become resistant to antimicrobials. Efflux pump inhibitors (EPIs) have recently emerged as a strategy to prevent the expulsion of administered antimicrobials, thereby resensitizing resistant bacteria to antibiotics. Phenylalanine-arginine β-naphthylamide (PAβN) is an EPI that inhibits a number of different pumps, including the MexAB-OprM efflux system. Despite EPIs providing a partial solution to AMR, they have been shown to be toxic to humans, which has impeded their entry into clinical application. We propose that by inserting the PAβN into a liposomal delivery system, the cytotoxic effects against human cells will be lowered without decreasing the EPI's inhibitory activity. Methods: Resistant P. aeruginosa strains will be administered with liposomes jointly encased with PAβN and ampicillin to ensure both are delivered to the same cell, while testing for changes in antimicrobial efflux activity and bacterial growth, indicative of restored antimicrobial effectiveness. Efflux activity and inhibited growth will be measured using an ethidium bromide efflux assay and a minimum inhibitory concentration assay, respectively. Human pulmonary epithelial cells will be exposed to liposomal-encased PAβN to study changes to EPI cytotoxicity, with cell viability being measured using a Cell Titer Blue assay. Results: Liposomal EPI are expected to maintain inhibitory activity and resistant bacteria would become re-susceptible to antibiotics when treated with the liposomal EPI. Discussion: By analyzing efflux rate to measure the liposomal EPI's activity, its activity level should be comparable to free EPI. The resensitization assay would show that the bacteria are susceptible to antibiotics again. Conclusion: If effective, EPIs may become a potential therapeutic to combat AMR by reviving the use of antimicrobials that have become ineffective. Restoring the activity of already approved antibiotics through potential co-administration with liposome-encapsulated EPIs will be a cost-effective approach to combat AMR.

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Liposomal Carrier Conjugated to APP-Derived Peptide for Brain Cancer Treatment

Cited by 26 publications

References 28 publications

Anticancer Mechanism of Curcumin on Human Glioblastoma

Anticancer Mechanism of Curcumin on Human Glioblastoma

Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue

Resurrecting the Dead: Mitigating Efflux-Pump Inhibitor Toxicity using a Liposomal Delivery System to Recover Efficacy of Antimicrobial Drugs

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