Apoptosis-inducing peptide loaded in PLGA nanoparticles induces anti-tumor effects in vivo

Priwitaningrum, Dwi; Jentsch, Julian; Bansal, Ruchi; Rahimian, Sima; Storm, Gert; Hennink, Wim E.; Prakash, Jai

doi:10.1016/j.ijpharm.2020.119535

Cited by 13 publications

(12 citation statements)

References 64 publications

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“…To prepare empty NPs and Cyanine 3 dye (Cy3)-labeled Smac-CPP loaded NPs, 100 µl PBS solution and 100 µl of Cy3-Smac-CPP were added as 7 internal water phase, respectively. Lyophilized Smac-CPP-loaded NPs were subsequently labeled with Cy3 for in vitro uptake study [132].…”

Section: Design Of Experiments (Doe) and Design Spacementioning

confidence: 99%

Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles

et al. 2021

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QbD approach empowers the pharma researchers to minimize the number of experimental trials and time. It helps identify the significant, influential factors such as critical material attributes, critical formulation variables, and critical process parameters, which may significantly impact the quality of the products. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable polymer, has gained an immense potential and wide range of applications as a carrier for manufacturing of polymeric nanoparticle drug delivery systems as per US-FDA and European Medicine Agency for drug delivery. The double emulsion method for preparing PLGA nanoparticles to encapsulate hydrophilic drugs has attracted interest in manufacturing processes. The double emulsion is a two-step process consisting of two different emulsification, making the process more complicated. The stability of nanoparticles obtained by a double emulsion method remains questionable due to the many formulations and process attributes. Currently, PLGA based nanoparticles prepared by a double emulsion technique are an alternative pharmaceutical manufacturing operation for getting the quality product by employing the Quality by Design approach. This present review has discussed the QbD elements to elucidate the effect of material attributes, formulation, and process variables on the critical quality attributes of the drug product, such as particle size distribution, encapsulation efficiency, etc. The components of a double emulsion, characteristics of drugs, polymers, and stabilizers used have been discussed in detail in this review. Graphic abstract

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Section: Design Of Experiments (Doe) and Design Spacementioning

confidence: 99%

Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles

et al. 2021

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“…Second mitochondria-derived activator of caspase (Smac) is another key pro-apoptotic pathway, activated with a Smac mimetic peptide. Priwitaningrum and his team [ 82 ] developed a nano-system to deliver a Smac peptide to tumors. They first synthesized a chimeric peptide that consists of the 8-mer Smac peptide and a 14-mer cell CPP and then encapsulated the Smac-CPP into polymeric nanoparticles (Smac-CPP-NPs).…”

Section: Delivery Of Proteins/enzymes Via Cpps For Cancer Treatmentmentioning

confidence: 99%

“…Combination treatment with Smac-CPP-NPs and dox reduced the tumor growth by 85%. This study demonstrated that the intracellular delivery of Smac-mimetic peptide by a CPP, using a nanoparticle system, could be a promising strategy to reduce tumor growth and to potentiate the therapeutic efficacy of chemotherapy in vivo [ 82 ].…”

Section: Delivery Of Proteins/enzymes Via Cpps For Cancer Treatmentmentioning

confidence: 99%

TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases

Lichtenstein

Zabit

Hauser

et al. 2021

Life

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Much effort has been dedicated in the recent decades to find novel protein/enzyme-based therapies for human diseases, the major challenge of such therapies being the intracellular delivery and reaching sub-cellular organelles. One promising approach is the use of cell-penetrating peptides (CPPs) for delivering enzymes/proteins into cells. In this review, we describe the potential therapeutic usages of CPPs (mainly trans-activator of transcription protein, TAT) in enabling the uptake of biologically active proteins/enzymes needed in cases of protein/enzyme deficiency, concentrating on mitochondrial diseases and on the import of enzymes or peptides in order to destroy pathogenic cells, focusing on cancer cells.

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“…[56][57][58] Studies had shown that the occurrence and development of tumors were apoptosis-related, and mitochondria had a regulatory effect on apoptosis. 59,60 Figure 4B and C, respectively, indicated the cumulative amount of the drug in the exfoliated mitochondria of CBRH-7919 cells, which was expressed by the amount of fluorescence intensity. After the cells were incubated with DLD/HYP-Lips for a period of time, the fluorescence intensity in the mitochondria was significantly higher than that in the SPC/HYP-Lips group.…”

Section: Hyp Content In Mitochondriamentioning

confidence: 99%

Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes

Feng¹,

Qin²,

Chang³

et al. 2021

IJN

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Introduction Hyperoside (HYP), a flavonol glycoside compound, has been shown to significantly inhibit the proliferation of malignant tumors. Mitochondria serve as both “energy factories” and “suicide weapon stores” of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Objective We report a novel dual-functional liposome system possessing both extracellular charge reversal and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of cancer cells. Methods L-lysine was used as a linker to connect 2,3-dimethylmaleic anhydride (DMA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a new compound, DSPE-Lys-DMA (DLD). Then, DLD was mixed with other commercially available lipids to form charge reversed and mitochondria-targeted liposomes (DLD-Lip). The size, morphology, zeta potential, serum stability, and protein adsorption of the HYP loaded DLD-Lip (HYP/DLD-Lip) were measured. The release profile, cellular uptake, in vitro and in vivo toxicity, and anticancer activity of HYP/DLD-Lip were investigated. Results The results showed that the mean diameter of the liposomes was less than 200 nm. The zeta potential of the liposomes was negative at pH 7.4. However, the zeta potential was positive at weak acidic pH values with the cleavage of the DMA amide. The charge reversion of HYP/DLD-Lip facilitated the cellular internalization and mitochondrial accumulation for enhanced antitumor effect. The strongest tumor growth inhibition (TGI 88.79%) without systemic toxicity was observed in DLD/HYP-Lips-treated CBRH-7919 tumor xenograft BALB/C mice. Conclusion The charge reversed and mitochondria-targeted liposomes represented a promising anticancer drug delivery system for enhanced anticancer therapeutic efficacy.

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Apoptosis-inducing peptide loaded in PLGA nanoparticles induces anti-tumor effects in vivo

Cited by 13 publications

References 64 publications

Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles

Quality by design prospects of pharmaceuticals application of double emulsion method for PLGA loaded nanoparticles

TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases

Antitumor Effect of Hyperoside Loaded in Charge Reversed and Mitochondria-Targeted Liposomes

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