Liposomal Drug Delivery Systems and Anticancer Drugs

Olusanya, Temidayo; Ahmad, Hayat; Ibegbu, Madu Daniel; Smith, James R.; Elkordy, Amal

doi:10.3390/molecules23040907

Cited by 462 publications

(272 citation statements)

References 103 publications

(123 reference statements)

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“…Many chemotherapeutic agents have been shown to induce severe systemic toxicity and several side effects due to their deficient pharmacokinetic profiles and non-specific distribution in the body [29]. In Yang et al's study [30], they have encapsulated honokiol into nanopolymers to enhance its permeability and specificity against cancer cells.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

132

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Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial-mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5 AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

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Section: In Vitro Studiesmentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

132

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“…Several liposomal drug formulations have been approved in the past 20 years. 16,17 Liposomes protect the encapsulated drugs from structural transformation or chemical degradation by isolating them from the surrounding environment and can provide targeted therapy to tumor cells. 18 It is difficult to formulate the SN38 liposome with high encapsulation efficiency (EE) because of the poor solubility of SN38 and its low affinity to the lipid membrane.…”

Section: Introductionmentioning

confidence: 99%

Novel SN38 derivative-based liposome as anticancer prodrug: an in vitro and in vivo study

Zhang

Yang

et al. 2018

IJN

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BackgroundMany novel drug delivery systems have been extensively studied to exploit the full therapeutic potential of SN38, which is one of the most potent antitumor analogs of camptothecins (CPTs), whose clinical application is seriously hindered by poor water solubility, low plasmatic stability, and severe toxicity, but results are always unsatisfactory.MethodsIn this study, combining the advantages of prodrug and nanotechnology, a lipophilic prodrug of SN38, SN38-PA, was developed by conjugating palmitic acid to SN38 via ester bond at C10 position, and then the lipophilic prodrug was encapsulated into a long-circulating liposomal carrier by film dispersion method.ResultsThe SN38-PA liposomes were characterized as follows: an average particle size of 80.13 nm, an average zeta potential of −33.53 mv, and the entrapment efficiency of 99%. Compared with CPT-11, SN38-PA liposome was more stable in close lactone form, more efficient in conversion rate to SN38, and more potent in cytotoxicity against tumor cells. Pharmacokinetic study showed that SN38-PA liposome had significantly enhanced plasma half-life (t1/2) value of SN38 and increased area under the curve (AUC) of SN38, which was 7.5-fold higher than that of CPT-11. Biodistribution study showed that SN38-PA liposome had more active metabolite SN38 in each tissue. Finally, the pharmacodynamic study showed that SN38-PA liposome had higher antitumor effect with the antitumor inhibition rate of 1.61 times than that of CPT-11.ConclusionThese encouraging data merit further investigation on this novel SN38-PA liposome.

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“…We found that, under these conditions, the loading capacity of each PLT was as high as 15~36 × 10 6 molecules of DOX and identified that loading was at its maximal 6 days after PC collection. This high loading is over 1000fold more than in a 100-nm liposome (10,000~15,000 molecules/liposome) [72], thanks to PLT size and, probably, the unique capacity of entrapment of DOX through the canalicular system [73][74][75]. For ease of clinical treatment, it is important that the PLT formulation can undergo long-term storage.…”

Section: Discussionmentioning

confidence: 99%

Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop

Huang

Changou

et al. 2020

J Biomed Sci

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Background: Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drugloaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed.Methods: PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at − 80°C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay.(Continued on next page) Results: 15~36 × 10 6 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX.Conclusions: Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.

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Liposomal Drug Delivery Systems and Anticancer Drugs

Cited by 462 publications

References 103 publications

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Novel SN38 derivative-based liposome as anticancer prodrug: an in vitro and in vivo study

Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop

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