NDLI: Multistep, effective drug distribution within solid tumors

Content Provider	PubMed Central
Author	Shemi, Amotz Khvalevsky, Elina Zorde Gabai, Rachel Malka Domb, Abraham Barenholz, Yechezkel
Copyright Year	2015
Abstract	The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack of blood and lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from a miniature drug source offers an alternative to both systemic delivery and intratumoral injection. Presented here is a model of drug distribution from such a source, in a multistep process. At delivery onset the drug mainly affects the closest surroundings. Such ‘priming’ enables drug penetration to successive cell layers. Tumor ‘void volume’ (volume not occupied by cells) increases, facilitating lymphatic perfusion. The drug is then transported by hydraulic convection downstream along interstitial fluid pressure (IFP) gradients, away from the tumor core. After a week tumor cell death occurs throughout the entire tumor and IFP gradients are flattened. Then, the drug is transported mainly by ‘mixing’, powered by physiological bulk body movements. Steady state is achieved and the drug covers the entire tumor over several months. Supporting measurements are provided from the LODER™ system, releasing siRNA against mutated KRAS over months in pancreatic cancer in-vivo models. LODER™ was also successfully employed in a recent Phase 1/2 clinical trial with pancreatic cancer patients.
Related Links	http://dx.doi.org/10.18632/oncotarget.5051
Ending Page	39577
Page Count	14
Starting Page	39564
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	37
Volume Number	6
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-11-01
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

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