Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo

Benjamin C. Tang; Jie Fu; D. Neil Watkins; Justin Hanes

doi:10.1016/j.biomaterials.2009.09.033

Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo

Benjamin C. Tang, Jie Fu, D. Neil Watkins, Justin Hanes

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer.

Original language	English (US)
Pages (from-to)	339-344
Number of pages	6
Journal	Biomaterials
Volume	31
Issue number	2
DOIs	https://doi.org/10.1016/j.biomaterials.2009.09.033
State	Published - Jan 2010

Keywords

Biodegradable polymers
Cancer
Controlled release
Drug delivery
Mucus-penetrating particles

ASJC Scopus subject areas

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

Access to Document

10.1016/j.biomaterials.2009.09.033

Cite this

@article{b3122af4d1b441b7b84052fcab548d95,

title = "Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo",

abstract = "Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer.",

keywords = "Biodegradable polymers, Cancer, Controlled release, Drug delivery, Mucus-penetrating particles",

author = "Tang, {Benjamin C.} and Jie Fu and Watkins, {D. Neil} and Justin Hanes",

note = "Funding Information: The authors thank Dr. Samuel Lai for expert advice and assistance in preparation of the manuscript. This work was supported in part by the NIH R21HL089816 (J.H), Flight Attendant Medical Research Institute (N.W), and NSF GK-12 BIGSTEP Fellowship (B.C.T). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, or the National Institutes of Health.",

year = "2010",

month = jan,

doi = "10.1016/j.biomaterials.2009.09.033",

language = "English (US)",

volume = "31",

pages = "339--344",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo

AU - Tang, Benjamin C.

AU - Fu, Jie

AU - Watkins, D. Neil

AU - Hanes, Justin

N1 - Funding Information: The authors thank Dr. Samuel Lai for expert advice and assistance in preparation of the manuscript. This work was supported in part by the NIH R21HL089816 (J.H), Flight Attendant Medical Research Institute (N.W), and NSF GK-12 BIGSTEP Fellowship (B.C.T). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, or the National Institutes of Health.

PY - 2010/1

Y1 - 2010/1

N2 - Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer.

AB - Drug carrier particles composed of poly(ethylene glycol)-co-poly(sebacic acid) (PEG-PSA) have been shown capable of efficient aerosolization into model lungs and the ability to rapidly penetrate human mucus. Here, we develop PEG-PSA particles (Etop/PEG-PSA) that encapsulate up to 40% etoposide by weight in a one step process, release it continuously for 6 days in vitro, and maintain its cytotoxic activity against a human lung tumor cell line in vitro. We further show that Etop/PEG-PSA injected intratumorally effectively suppress human lung tumor growth in a xenograft mouse model, with 100% survival after 31 days. In contrast, 0% survival was observed by day 24 in animals that received free etoposide (either intratumoral or intraperitoneal administration) or placebo particles intratumorally. These findings support PEG-PSA as a drug delivery platform for improved local therapy of cancer.

KW - Biodegradable polymers

KW - Cancer

KW - Controlled release

KW - Drug delivery

KW - Mucus-penetrating particles

UR - http://www.scopus.com/inward/record.url?scp=70350709937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350709937&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2009.09.033

DO - 10.1016/j.biomaterials.2009.09.033

M3 - Article

C2 - 19796810

AN - SCOPUS:70350709937

SN - 0142-9612

VL - 31

SP - 339

EP - 344

JO - Biomaterials

JF - Biomaterials

IS - 2

ER -

Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this