Trojan Horse Meets Magic Bullet to Spawn a Novel, Highly Effective Drug Delivery Model

Lacko, Andras G.; Nair, Maya; Paranjape, Sulabha; Mooberry, Linda; McConathy, Walter J.

doi:10.1159/000093268

Cited by 32 publications

(39 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10,11,15 As shown in Figure 4, there was a substantial decrease in the uptake of AD-32 from the AD-32 containing rHDL nanoparticles by the malignant cells (PC-3 and SKOV-3), in response to the progressively increasing HDL concentrations in the incubation mix. The nonmalignant cells (PZ-HPV and HiO180), however, showed a much more limited response to increasing HDL, consistent with their lower expression of the SR-B1 receptor.…”

Section: Uptake Of Ad-32 From Rhdl Particles By Malignant and Nonmalimentioning

confidence: 90%

“…21,34 Here, we report an attempt to overcome this solubility barrier by encapsulating the AD-32 in rHDL nanoparticles. [11][12][13][14][15][16] The advantageous characteristics of HDL-based drug carriers include small size, selective delivery via receptor targeting, stability during storage, and high payload capacity. [11][12][13][14][15][16] Encapsulation of lipophilic drugs within nanocarriers has shown great potential as an alternative or an adjunct to existing chemotherapy regimens.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16] The advantageous characteristics of HDL-based drug carriers include small size, selective delivery via receptor targeting, stability during storage, and high payload capacity. [11][12][13][14][15][16] Encapsulation of lipophilic drugs within nanocarriers has shown great potential as an alternative or an adjunct to existing chemotherapy regimens. 4,5 In addition, the selective targeting of malignant cells through receptor-mediated uptake of anticancer drugs 13,14 is a key concept in mediating or eliminating the side effects of conventional chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The nonmalignant cells (PZ-HPV and HiO180), however, showed a much more limited response to increasing HDL, consistent with their lower expression of the SR-B1 receptor. [10][11][12]14,15.…”

Section: Uptake Of Ad-32 From Rhdl Particles By Malignant and Nonmalimentioning

confidence: 99%

“…[6][7][8] Encapsulation of drugs within the reconstituted high-density lipoprotein (rHDL) nanocarriers has shown great potential for cancer chemotherapy by minimizing limitations encountered with conventional formulations, including LNs and liposomes. [9][10][11] The rHDL nanoparticles have been identified as an effective drug-delivery system for highly lipophilic drugs the delivery of the drug to cancer cells and tumors occurs via a targeted, receptor-mediated mechanism involving the scavenger receptor class B type 1 (SR-B1). [13][14][15][16] The current study was undertaken to evaluate the in vitro therapeutic eff icacy of valrubicin [AD-32 (N-trifluoroacetyladriamycin-14-valerate)], a derivative of doxorubicin, which was originally developed as a cancer therapeutic agent, [17][18][19] leading to its restricted approval for treating Bacillus Calmette-Guerin (BCG)-resistant bladder cancers in 1998.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Sabnis¹,

Nair²,

Israel³

et al. 2012

IJN

View full text Add to dashboard Cite

Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC 50 ) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC 50 doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor-mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at -20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent.

show abstract

Section: Uptake Of Ad-32 From Rhdl Particles By Malignant and Nonmalimentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Uptake Of Ad-32 From Rhdl Particles By Malignant and Nonmalimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Sabnis¹,

Nair²,

Israel³

et al. 2012

IJN

View full text Add to dashboard Cite

show abstract

Targeting Interferon‐α to the Liver: Apolipoprotein A‐I as a Scaffold for Protein Delivery

Fioravanti

Prìeto

Berraondo

2013

Fusion Protein Technologies for Biopharmaceuticals

View full text Add to dashboard Cite

Characterization of woodchuck apolipoprotein A‐I: A new tool for drug delivery and identification of altered isoforms in the woodchuck chronic hepatitis model

Fioravanti

Gomar

Medina-Echeverz

et al. 2011

Journal of Medical Virology

View full text Add to dashboard Cite

Apolipoprotein A-I (ApoA-I) is the major protein component of high density lipoprotein (HDL) particles in serum, and participates in the reverse transport of cholesterol from tissues to the liver for excretion. The natural HDL tropism to the liver and cancer cells has been used extensively to target encapsulated drugs. The alteration of the plasmatic isoforms of ApoA-I is a hallmark of chronic hepatitis and hepatocarcinoma in mice and humans. Woodchucks infected with the woodchuck hepatitis virus (WHV) represent the best animal model for the study of chronic viral hepatitis B and viral induced hepatocarcinoma (HCC). WHV-infected woodchuck represents a clinically relevant animal model under which new treatment strategies can be evaluated and optimized. Therapeutic efficacy in this model is likely to be translated into a successful therapy for patients infected with HBV. The present study describes, for the first time, the cloning and characterization of woodchuck ApoA-I. The open reading frame (ORF) of the woodchuck ApoA-I is 795 bp long, coding for 264 amino acids. Unexpectedly, phylogenetic analysis revealed that the closest sequences are those of human and macaque. Woodchuck HDLs were isolated successfully from sera by density gradient ultracentrifugation. A commercial antibody that recognized the woodchuck ApoA-I was also identified. Finally, taking advantage of the techniques and tools developed in this study, two potential applications of woodchuck HDLs are illustrated: drug delivery to a woodchuck hepatocarcinoma cell line and the use of isoelectrofocusing to identify ApoA-I isoforms.

show abstract

Trojan Horse Meets Magic Bullet to Spawn a Novel, Highly Effective Drug Delivery Model

Abstract: Because of their physicochemical properties and the selective receptor-mediated uptake of their core components, reconstituted high-density lipoproteins have unique advantages over conventional formulations to serve as targeted drug delivery agents.

Cited by 32 publications

References 30 publications

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Targeting Interferon‐α to the Liver: Apolipoprotein A‐I as a Scaffold for Protein Delivery

Characterization of woodchuck apolipoprotein A‐I: A new tool for drug delivery and identification of altered isoforms in the woodchuck chronic hepatitis model

Contact Info

Product

Resources

About