A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the intestine: In-vivo and in-vitro evaluation of an indomethacin–lecithin conjugate

Dahan, Arik; Duvdevani, Revital; Dvir, Eran; Elmann, Anat; Hoffman, Amnon

doi:10.1016/j.jconrel.2006.12.032

Cited by 52 publications

(64 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other investigators considered phospholipid prodrugs for improved oral delivery of indomethacin and valproic acid 49,50. In those studies, Sn2 phospholipid conjugates were utilized to affect oral controlled release of drugs by continuous degradation of the phospholipid prodrug within the intestine.…”

Section: Phospholipid Sn2 Prodrugs With Liposomesmentioning

confidence: 99%

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Pan

Pham

Weilbaecher

et al. 2015

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a ‘magic bullet’ to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin-walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a ‘Grail Quest’ by its loyal opposition and even many in the field adsorbing the pains of a long-learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made ‘made the turn’ toward meaningful translational success.

show abstract

Section: Phospholipid Sn2 Prodrugs With Liposomesmentioning

confidence: 99%

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Pan

Pham

Weilbaecher

et al. 2015

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

show abstract

“…Anti-HIV activity and cytotoxicity were evaluated against HIV-1 strain (III B ) and HIV-2 strain (ROD) in MT-4 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method [24][25][26]. First, MT-4 cells were suspended in culture medium at 1 × 10 5 cells/mL and infected with HIV at a multiplicity of infection (MOI) of 0.02.…”

Section: Anti-hiv Activity Assaymentioning

confidence: 99%

Synthesis, drug release and anti-HIV activity of a series of PEGylated zidovudine conjugates

Zhan

et al. 2012

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

“…HPLC was used for determining the precise amount of indomethacin, ibuprofen, DP-155, and DP-499 before treating the cells, as previously described (Dahan et al 2007).…”

Section: Hplc Analysismentioning

confidence: 99%

³¹P Magnetic Resonance Spectroscopy of Endothelial Cells Grown in Three-Dimensional Matrigel Constructs as an Enabling Platform Technology: II. The Effect of Anti-Inflammatory Drugs on Phosphometabolite Levels

Ringel¹,

Lecht²,

Sterin³

et al. 2008

Endothelium

View full text Add to dashboard Cite

In the accompanying study, the authors presented phosphometabolite patterns of endothelial cells grown under three-dimensional (3D) conditions using (31)P magnetic resonance spectroscopy (MRS). Here the authors describe the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), using this enabling platform technology, which is relevant for evaluating drug effects in tissue-engineered endothelial constructs. Treatment with indomethacin significantly changed the phosphometabolite fingerprint in this endothelial model, by, respectively, increasing (81%) and decreasing (42%) glycerophosphocholine (GPC) and phosphomonoesters (PM). Furthermore, a safer approach using a NSAID prodrug was also demonstrated in this study with a indomethacin phospholipid-derived prodrug (DP-155). Like the parental drug, DP-155 increased and decreased the levels of GPC and PM by 100% and 20%, respectively. These changes represent useful biomarkers to monitor NSAID effects on endothelized tissue-engineered constructs for the purpose of controlling endothelial cell survival and inflammation upon implantation.

show abstract

A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the intestine: In-vivo and in-vitro evaluation of an indomethacin–lecithin conjugate

Cited by 52 publications

References 27 publications

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Synthesis, drug release and anti-HIV activity of a series of PEGylated zidovudine conjugates

³¹P Magnetic Resonance Spectroscopy of Endothelial Cells Grown in Three-Dimensional Matrigel Constructs as an Enabling Platform Technology: II. The Effect of Anti-Inflammatory Drugs on Phosphometabolite Levels

Contact Info

Product

Resources

About

A novel mechanism for oral controlled release of drugs by continuous degradation of a phospholipid prodrug along the intestine: In-vivo and in-vitro evaluation of an indomethacin–lecithin conjugate

Cited by 52 publications

References 27 publications

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

Synthesis, drug release and anti-HIV activity of a series of PEGylated zidovudine conjugates

31P Magnetic Resonance Spectroscopy of Endothelial Cells Grown in Three-Dimensional Matrigel Constructs as an Enabling Platform Technology: II. The Effect of Anti-Inflammatory Drugs on Phosphometabolite Levels

Contact Info

Product

Resources

About

³¹P Magnetic Resonance Spectroscopy of Endothelial Cells Grown in Three-Dimensional Matrigel Constructs as an Enabling Platform Technology: II. The Effect of Anti-Inflammatory Drugs on Phosphometabolite Levels