Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes

Bertrand, Nicolas; Fleischer, Jackie G.; Wasan, Kishor M.; Leroux, Jean‐Christophe

doi:10.1016/j.biomaterials.2008.12.082

Cited by 62 publications

(46 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The optimisation of NPs’ efficacy therefore also involves optimal drug release rates whether through controlled diffusional release [135], covalent conjugation of the drug to a polymer backbone [136, 137] or environment-triggered release [138, 139]. Without specific affinity of the nanomaterial for the cancer cells, the chemotherapeutic payloads will have to reach their pharmacological targets by their own means or risk diffusing back into the vasculature [77].…”

Section: Passive Targeting: Nearly 30 Years Of the Epr Effect…mentioning

confidence: 99%

Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

Bertrand

et al. 2014

Advanced Drug Delivery Reviews

Self Cite

2,422

1,814

View full text Add to dashboard Cite

Cancer nanotherapeutics are progressing at a steady rate; research and development in the field has experienced an exponential growth since early 2000’s. The path to the commercialization of oncology drugs is long and carries significant risk; however, there is considerable excitement that nanoparticle technologies may contribute to the success of cancer drug development. The pace at which pharmaceutical companies have formed partnerships to use proprietary nanoparticle technologies has considerably accelerated. It is now recognized that by enhancing the efficacy and/or tolerability of new drug candidates, nanotechnology can meaningfully contribute to create differentiated products and improve clinical outcome. This review describes the lessons learned since the commercialization of the first-generation nanomedicines including DOXIL® and Abraxane®. It explores our current understanding of targeted and non-targeted nanoparticles that are under various stages of development, including BIND-014 and MM-398. It highlights the opportunities and challenges faced by nanomedicines in contemporary oncology, where personalized medicine is increasingly the mainstay of cancer therapy. We revisit the fundamental concepts of enhanced permeability and retention effect (EPR) and explore the mechanisms proposed to enhance preferential “retention” in the tumor, whether using active targeting of nanoparticles, binding of drugs to their tumoral targets or the presence of tumor associated macrophages. The overall objective of this review is to enhance our understanding in the design and development of therapeutic nanoparticles for treatment of cancers.

show abstract

Section: Passive Targeting: Nearly 30 Years Of the Epr Effect…mentioning

confidence: 99%

Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

Bertrand

et al. 2014

Advanced Drug Delivery Reviews

Self Cite

2,422

1,814

View full text Add to dashboard Cite

show abstract

“…Hydrolysis over time increases LCST [16]. For in situ PNDJ, when the LCST increases above body temperature, the hydrogel dissolves and is cleared by renal excretion [8].…”

Section: Gel Synthesis and Characterizationmentioning

confidence: 99%

“…Importantly, renal excretion is expected from both PNDJ polymer and gentamicin [8,19,43] and could cause nephrotoxicity. It is therefore necessary to determine the level of systemic exposure to gentamicin and to evaluate the renal effects of locally delivered G-PNDJ hydrogels.…”

Section: Introductionmentioning

confidence: 99%

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Overstreet

McLaren

Calara

et al. 2015

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

Background Local delivery can achieve the high antimicrobial concentrations necessary to kill biofilm-related microbes. Degradation times for resorbable carriers are too long. Hydrogels (gels of hydrophilic polymer in water) can degrade faster but release antimicrobials too quickly. We previously developed hydrogels based on the copolymer poly(N-isopropylacrylamide-co-dimethyl-c-butyrolactone acrylate-co-Jeffamine 1 M-1000 acrylamide) (PNDJ) with delivery times of several days with complete degradation in less than 6 weeks. Questions/purposes We asked: (1) What is the elution profile of gentamicin from PNDJ hydrogels? (2) Is gentamicin released from gentamicin-loaded PNDJ (G-PNDJ) hydrogel effective for treatment of orthopaedic infection? (3) Does local gentamicin delivery from G-PNDJ hydrogel cause renal dysfunction? Methods (1) Two formulations of G-PNDJ, lower dose (1.61 wt%) and higher dose (3.14 wt%), five samples each, were eluted in buffered saline under infinite sink conditions. (2) Infections were induced in 16 New Zealand White rabbits by inserting a Kirschner wire in a devascularized radius segment and inoculating with 7.5 9 10 6 colony-forming units Staphylococcus aureus. At 3 weeks, débridement was performed and a new Kirschner wire was placed in the dead space. Treatment was randomized to higher-dose G-PNDJ or no hydrogel. No systemic antimicrobials were used. Positive culture and acute inflammation on histology were used to determine the presence of infection 4 weeks postdébridement. (3) 3.14 wt% G-PNDJ, 0.75, 1.5, or 3.0 mL, was injected subcutaneously in nine Sprague-Dawley rats, three of each dose. Serum gentamicin, blood urea nitrogen, and creatinine were measured on Days 1, 3, 7, 14, and 28. Results (1) Gentamicin release was sustained over 7 days with the higher-dose formulation release profile similar to release from high-dose antimicrobial-loaded bone cement.(2) Four weeks postdébridement, infection was present in eight of eight no-hydrogel rabbits but zero of eight rabbits treated with G-PNDJ hydrogel (p \ 0.001). (3) Blood urea nitrogen and creatinine were transiently elevated

show abstract

“…Alternatively, it was shown that the terminally alkylated NIPAM copolymer provided a steric barrier that enhanced, although marginally, the liposome circulation time in vivo (Roux et al, 2002b). The combination of both the terminally alkylated NIPAM copolymer and a PEGylated lipid in the vesicle structure was found to provide liposomes with both strong pH-responsive properties and a long half-life (Bertrand et al, 2009;Roux et al, 2004). This manuscript reports the in vitro evaluation and characterization of pH-sensitive liposomes based on NIPAM copolymers for the delivery of ara-C.…”

Section: Introductionmentioning

confidence: 95%

pH-sensitive immunoliposomes specific to the CD33 cell surface antigen of leukemic cells

Simard

Leroux

2009

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes

Cited by 62 publications

References 45 publications

Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

pH-sensitive immunoliposomes specific to the CD33 cell surface antigen of leukemic cells

Contact Info

Product

Resources

About