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

Dipanjan Pan; Christine T N Pham; Katherine N Weilbaecher; Michael H Tomasson; Samuel A Wickline; Gregory M Lanza

doi:10.1002/wnan.1355

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

Journal article

Open access

Peer reviewed

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

Dipanjan Pan, Christine T N Pham, Katherine N Weilbaecher, Michael H Tomasson, Samuel A Wickline and Gregory M Lanza

Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, Vol.8(1), pp.85-106

01/2016

DOI: 10.1002/wnan.1355

PMCID: PMC4709477

PMID: 26296541

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Abstract

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.

Animals

Drug Delivery Systems

Humans

Lipase

Lipids

Liposomes

Mice

Nanoparticles

Prodrugs

Details

Title: Subtitle: Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery
Creators: Dipanjan Pan - University of Illinois Urbana-Champaign
Christine T N Pham - Washington University in St. Louis
Katherine N Weilbaecher - Washington University in St. Louis
Michael H Tomasson - Washington University in St. Louis
Samuel A Wickline - Washington University in St. Louis
Gregory M Lanza - Washington University in St. Louis
Resource Type: Journal article
Publication Details: Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, Vol.8(1), pp.85-106
DOI: 10.1002/wnan.1355
PMID: 26296541
PMCID: PMC4709477
NLM abbreviation: Wiley Interdiscip Rev Nanomed Nanobiotechnol
ISSN: 1939-5116
eISSN: 1939-0041
Grant note: R01 CA154737 / NCI NIH HHS U54 CA199092 / NCI NIH HHS R01 AR067491 / NIAMS NIH HHS R01 HL113392 / NHLBI NIH HHS
Language: English
Date published: 01/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984359949702771

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