scholarly journals Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles

Nanoscale ◽  
2016 ◽  
Vol 8 (13) ◽  
pp. 6948-6957 ◽  
Author(s):  
Marilena Hadjidemetriou ◽  
Zahraa Al-Ahmady ◽  
Kostas Kostarelos
Keyword(s):  
Time Evolution ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Protein Corona

Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3058-3065 ◽  
Author(s):  
Robert Z. Orlowski ◽  
Peter M. Voorhees ◽  
Reynaldo A. Garcia ◽  
Melissa D. Hall ◽  
Fred J. Kudrik ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Liposomal Doxorubicin ◽  
Phase 1 ◽  
Pegylated Liposomal Doxorubicin ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Maximum Tolerated Dose ◽  
Chemotherapeutic Agents

Abstract Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and pharmacodynamic studies did not find significant drug interactions between these agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen.

scholarly journals PEGylated Liposomes Remotely Loaded with the Combination of Doxorubicin, Quinine, and Indocyanine Green Enable Successful Treatment of Multidrug-Resistant Tumors

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2181
Author(s):  
Emma Grabarnick (Portnoy) ◽  
Alexander V. Andriyanov ◽  
Hadas Han ◽  
Sara Eyal ◽  
Yechezkel Barenholz
Keyword(s):  
Indocyanine Green ◽  
Cancer Cells ◽  
Liposomal Doxorubicin ◽  
Therapeutic Potential ◽  
Combined Treatment ◽  
Pegylated Liposomal Doxorubicin ◽  
Scanning Calorimetry ◽  
Transmission Microscopy ◽  
Ht 29

Multidrug resistance (MDR) of cancer cells remains a major obstacle to favorable outcomes of treatment with many drugs, including doxorubicin. Most of the clinical trials failed to demonstrate the benefit of the drug efflux transporter P-glycoprotein (P-gp) inhibitors to circumvent P-gp-mediated drug resistance in vivo. The present study explored the therapeutic potential of combined treatment with liposomal doxorubicin, P-gp inhibitor quinine, and the photodynamic therapy (PDT) using indocyanine green (ICG) in the adenocarcinoma drug-resistant tumor model. Liposomes were actively co-remotely loaded with doxorubicin and quinine, and ICG was passively adsorbed. The liposomes were characterized by differential scanning calorimetry (DSC) and cryogenic transmission microscopy (Cryo-TEM). We found that quinine impaired the crystalline structure of doxorubicin. In vitro, treatment with single agents themselves was insufficient to inhibit the growth of HT-29 MDR1 cells. However, pegylated liposomal doxorubicin and quinine (PLDQ) significantly diminished HT-29 MDR1 cell survival. Furthermore, survival inhibition intensified by the addition of ICG to the PLDQ (ICG + PLDQ). In vivo, ICG + PLDQ significantly decreased tumor growth when combined with tumor irradiation with NIR light (** p < 0.01). ICG + PLDQ + irradiation was superior to single treatments or combinational treatments without irradiation. These findings suggest that ICG + PLDQ can overcome P-gp-mediated MDR in cancer cells.

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