Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus

Kuai, Qiyuan; Wang, Yu; Gao, Fenghua; Qi, Yingqiu; Wang, Rui; Wang, Yanbing; Lu, Xiaofan; Zhao, Ying; Nie, Guangjun; He, Min; Zhou, Hong Jing; Jiang, Xingwei; Ren, Suping; Yu, Qun

doi:10.1166/jbn.2019.2764

Cited by 12 publications

(9 citation statements)

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“…NSG mice (NOD- Prkdc scid Il2rg em1 /Smoc , NM-NSG-001) 52 - 54 aged 6 weeks were purchased from Shanghai Model Organisms. NSG mice were transplanted with 1 × 10 7 ACH2 cells or J-Lat 10.6 cells in a volume of 200 µL PBS by tail vein injection.…”

Section: Methodsmentioning

confidence: 99%

EK-16A liposomes enhance HIV replication in ACH2 or J-Lat 10.6 cell engrafted NSG mice

Lu¹,

Yang²,

Yang³

et al. 2022

Nanotheranostics

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Background: Numbers of HIV latency reversal agents (LRAs) have been tested in clinical trials, but with limited effect. EK-16A is an ingenol derivative that isolated from Euphorbia kansui . Our prior studies have suggested that it could reactivate latent HIV and meanwhile inhibit HIV infection in vitro . Here, we further advanced the research in vivo . Methods: In vitro , the activity of EK-16A liposomes was measured in HIV latently infected cells. In serum pharmacology test, BALB/c mice were orally administered with EK-16A liposomes, serum was separated and co-cultured with cells, HIV reactivation was measured. In vivo , NSG mice were transplanted with human cells for 3 weeks and then administered with EK-16A liposomes for 3 days. In ACH2 cell engrafted NSG mice, P24 in plasma and cell-associated HIV RNA in tissues was measured. In J-Lat 10.6 cell engrafted NSG mice, GFP expression of J-Lat 10.6 cells in diverse tissues was measured. Hematoxylin and eosin (HE) staining was carried out for histopathological examination in both mice. Results: EK-16A liposomes can reactivate latent HIV in ACH2 and J-Lat 10.6 cells. Serum pharmacological test showed that EK-16A retained activity after oral administration. Importantly, in ACH2 cell engrafted NSG mice, EK-16A liposomes increased the secretion of P24 in plasma and the expression of cell-associated HIV RNA in tissues. In J-Lat 10.6 cell engrafted NSG mice, EK-16A liposomes increased the GFP expression of J-Lat 10.6 cells in diverse tissues, including the bone marrow, spleen, liver, lung and peripheral blood. Furthermore, there was no obvious histopathological change associated with the use of EK-16A liposomes in both mice. Conclusions: Our results confirmed the enhancing HIV replication activity and preliminary security of EK-16A in human cell engrafted NSG mice, laying the foundation for research in clinical trials.

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Section: Methodsmentioning

confidence: 99%

EK-16A liposomes enhance HIV replication in ACH2 or J-Lat 10.6 cell engrafted NSG mice

Lu¹,

Yang²,

Yang³

et al. 2022

Nanotheranostics

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“…14,[167][168][169]171 Although this is a valuable approach for drugs that can be delivered to the cell surface, in this review, we focus on strategies for nanoparticle-mediated intracellular drug delivery to T cells, noting that most reported studies originate from the field of oncology 19,26,140,144,[172][173][174][175][176][177] and HIV. [178][179][180][181][182][183] For a detailed listing of the studies described in this section, see Table 2.…”

Section: Nanoparticle-mediated Drug Delivery To T Cells: Successes To...mentioning

confidence: 99%

“…Despite the importance of T cells in various diseases, there are relatively few studies exploring direct T cell-targeted drug delivery using nanoparticles. Most reports focus on drug delivery to the T cell surface, thus not requiring nanoparticle internalization. ,− , Although this is a valuable approach for drugs that can be delivered to the cell surface, in this review, we focus on strategies for nanoparticle-mediated intracellular drug delivery to T cells, noting that most reported studies originate from the field of oncology ,,,,− and HIV. − For a detailed listing of the studies described in this section, see Table .…”

Section: Nanoparticle-mediated Drug Delivery To T Cells: Successes To...mentioning

confidence: 99%

“…Only a selection of these studies discuss the mechanism of drug release from the nanomaterial. Most of the studies report a sustained drug release over time, ,,,, which in one study is shown to be further triggered after nanoparticle internalization . Drug release from gold nanoparticles has been described to be pH-dependent , or triggered by endosomal cleavage of the nanoparticle shell …”

Section: Nanoparticle-mediated Drug Delivery To T Cells: Successes To...mentioning

confidence: 99%

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In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design

et al. 2021

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T cells play an important role in immunity and repair and are implicated in diseases, including blood cancers, viral infections, and inflammation, making them attractive targets for the treatment and prevention of diseases. Over recent years, the advent of nanomedicine has shown an increase in studies that use nanoparticles as carriers to deliver therapeutic cargo to T cells for ex vivo and in vivo applications. Nanoparticle-based delivery has several advantages, including the ability to load and protect a variety of drugs, control drug release, improve drug pharmacokinetics and biodistribution, and site-or cell-specific targeting. However, the delivery of nanoparticles to T cells remains a major technological challenge, which is primarily due to the nonphagocytic nature of T cells. In this review, we discuss the physiological barriers to effective T cell targeting and describe the different approaches used to deliver cargo-loaded nanoparticles to T cells for the treatment of disease such as T cell lymphoma and human immunodeficiency virus (HIV). In particular, engineering strategies aiming to improve nanoparticle internalization by T cells, including ligand-based targeting, will be highlighted. These nanoparticle engineering approaches are expected to inspire the development of effective nanomaterials that can target or manipulate the function of T cells for the treatment of T cell-related diseases.

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“…It is possible to use alternate processing and speci c formulation techniques if these properties prevent the development of a drug formulation [15,16]. Through the oral route, As a result of nanotechnology, the limitations of conventional capsules overcame by presenting the medications as polymeric nanoparticles [17], nanocrystals [18,5], peptide nanoparticles [19], nano-micelles [20], liposomes [21,22] etc. To circumvent the issues discussed previously, liposomal formulations are being considered as potential substitutes for increasing NE's oral bioavailability [12] [23].…”

Section: Introductionmentioning

confidence: 99%

Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

Kala

Chinni²

2022

Preprint

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PurposeNintedanib esylate (NE) is a kinase inhibitor designated for the cure of non-small cell lung cancer suffers from first-pass metabolism which resulted in low oral bioavailability (~4.7%). The intent of this exploration was to increase the oral bioavailability of NE by means of TPGS coated liposomes. MethodsThe NE-loaded TPGS coated liposomes were formulated by high-speed homogenization by optimizing process parameters like phospholipids: cholesterol molar ratio, drug loading and sonication time through the design of experiments. The drug's behaviour was studied using a variety of techniques, including physicochemical characterization, in-vitro and in-vivo studies. ResultsThe NE-liposomes had a particle size of 125±6.68 nm, entrapment efficiency of 88.64±4.12% and zeta potential of +46±2.75 mV. X-ray diffraction analysis revealed that NE had been converted to an amorphous state, while transmission electron microscope images showed spherical shape and smooth coating of TPGS on surface of liposomes. The formulation showed Higuchi kinetics with sustained drug release of 88.72 ± 3.40% in 24 hours. Cellular uptake of C-6 labelled liposomes was observed in A-549 cells and cytotoxicity testing revealed that NE-liposomes were more effective than marketed formulation Ofev®. Formulation remained in simulated fluids and for three months in stability chamber and. Liposomal oral bioavailability was ~6.23 times greater in sprague dawley male rats compared to marketed formulation Ofev®, according to in-vivo pharmacokinetic data. ConclusionNE-Liposomal formulations are better for oral administration compared to the marketed capsules because of the prolonged drug release and increased oral bioavailability as a result, the developed formulation can become a successful strategy in cancer chemotherapy.

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Peptide Self-Assembly Nanoparticles Loaded with Panobinostat to Activate Latent Human Immunodeficiency Virus

Cited by 12 publications

References 0 publications

EK-16A liposomes enhance HIV replication in ACH2 or J-Lat 10.6 cell engrafted NSG mice

EK-16A liposomes enhance HIV replication in ACH2 or J-Lat 10.6 cell engrafted NSG mice

In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design

Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

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