Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat. Toxicol Appl Pharmacol

Risk Science Center, Department of Environmental Health Sciences, 109 S Observatory, University of Michigan School of Public Health, Ann Arbor, MI 48109-2029, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 12/2010; 251(3):181-90. DOI: 10.1016/j.taap.2010.11.017
Source: PubMed


A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles (~31 nm average diameter). PAA NPs and polyethylene glycol-coated PAA NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 min to 120 h and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43 h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120 h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000%-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non-pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage.

Download full-text


Available from: Yvan Wenger,
58 Reads
  • Source
    • "Several In vitro studies have revealed that polyacrylamide gels are biocompatibles (Karadaǧ et al. 1996; Risbud and Bhonde 2000). Polyacrylamide gels also exhibit excellent biocompatibility In vivo (Gin et al. 1990; Saraydin et al. 2004; Wenger et al. 2011). Polyacrylamide hydrogels with pH-sensitive swelling have been used with excellent results as carriers in drug delivery research (Gupta et al. 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral administration of specific egg yolk immunoglobulin (IgY) is effective against a number of gastrointestinal pathogens. However, the activity of orally administered IgY is reduced rapidly, since IgY is sensitive to pepsin and low pH. In this study, hydrogels containing acrylamide and acrylic acid were synthesized and used to encapsulate IgY. The capacity of these structures to load, protect and release IgY and the interaction between IgY and hydrogels by FTIR spectroscopy were studied. The particle size and swelling percentage of hydrogels were highly dependent on the pH of the buffer solution. As expected, pH-sensitive hydrogels had a high IgY loading percentage (99.2 ± 12.9 mg IgY/mg hydrogel) at pH 7.4. It means that each gel piece incorporated approximately 8.4 ± 1.1 mg IgY. The results showed that the hydrogels could efficiently incorporate IgY and retain it inside the polymer network at pH <2.2. However, IgY was slowly released at basic pH and a high percentage remained inside. The IR spectra show that IgY interacts with the hydrogel in its network with extended hydrogen bonds. The present study demonstrates that hydrogels particles can efficiently incorporate the IgY but cannot show a controlled and sustained release of IgY in simulated intestinal fluid probably due to hydrophobic interactions with the polymer network. The stability of IgY in simulated gastric fluid was greatly improved by encapsulation in hydrogels. This approach provides information about a novelty method for delivery of IgY for the prevention and control of enteric diseases.
    Journal of Food Science and Technology -Mysore- 04/2014; 52(5):1-6. DOI:10.1007/s13197-014-1337-3 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT.
    Lasers in Surgery and Medicine 09/2011; 43(7):686-95. DOI:10.1002/lsm.21113 · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: New higly unsaturated macrocyclic building blocks [CuLSCN]·ClO4 (1) (L=N-dl-5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene) and [NiL(SCN)2] (2) (L=N-dl-5,12-dimethyl-7,14-diisopropyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene) were synthesized and the crystal structures of both compounds were determined. Both complexes crystallizes in monoclinic, space group P21/n (1) and P21/c (2). Their magnetic properties were studied over the temperature range 1.8–300K using a Quantum Design SQUID magnetometer (MPMSXL-5-type). The results indicate that both compounds behave as weakly interacting paramagnetic centers in the crystal lattice. The effects of hydrogen bond mediating the magnetic exchange interactions on the spin density have been evidenced by DFT calculations. The NIR–Vis–UV diffuse-reflectance electronic spectra confirm the square pyramidal and octahedral geometry around Cu2+ and Ni2+ metal ions.
    Polyhedron 09/2011; 30(15):2550-2557. DOI:10.1016/j.poly.2011.06.031 · 2.01 Impact Factor
Show more