Acid Dnase Activities In Peripheral, Mononuclear Blood Cells: A Possible Parameter To Detect Proliferating Cell Populations

Reitz, M.; Gutjahr, P.

doi:10.1515/znc-1992-11-1219

Cited by 1 publication

(1 citation statement)

References 11 publications

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“…6). Since it was widely reported that blood contains significant levels of DNases (28, 29), it was reasonable to expect that fast degradation of DNA in blood will occur. Degradation of naked DNA and DNA in rPLL/DNA polyplex, rSDN, and RGD-rSDN was determined by mixing the formulations with freshly isolated heparinized mouse blood (Fig.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Pharmacokinetics of Bioreducible Gene Delivery Vectors by Real-time PCR

Zhou

Manickam

et al. 2009

Pharm Res

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Purpose To investigate pharmacokinetics of reversibly stabilized DNA nanoparticles (rSDN) using a single-step lysis RT-PCR. Methods rSDN were prepared by coating bioreducible polycation/DNA polyplexes with multivalent N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. Targeted polyplexes were formulated by linking cyclic RGD ligand (c(RGDyK)) to the HPMA surface layer of rSDN. The pharmacokinetic parameters in tumor-bearing mice were analyzed by PKAnalyst®. Results The pharmacokinetics of naked plasmid DNA, simple DNA polyplexes, rSDN, and RGD-targeted rSDN exhibited two-compartment model characteristics with area under the blood concentration–time curve (AUC) increasing from 1,102 ng·ml−1·min−1 for DNA to 3,501 ng·ml−1·min−1 for rSDN. Non-compartment model analysis revealed increase in mean retention time (MRT) from 4.5 min for naked DNA to 22.9 min for rSDN. Conclusions RT-PCR is a sensitive and convenient method suitable for analyzing pharmacokinetics and biodistribution of DNA polyplexes. Surface stabilization of DNA polyplexes can significantly extend their MRT and AUC compared to naked DNA. DNA degradation in rSDN in blood circulation, due to a combined effect of disulfide reduction and competitive reactions with charged molecules in the blood, contributes to DNA elimination.

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Section: Resultsmentioning

confidence: 99%