Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA–mPEG nanoparticles

Panagi, Z.; Beletsi, A.; Evangelatos, Gregory P.; Livaniou, Evangelia; Ithakissios, Dionyssis S.; Avgoustakis, Konstantinos

doi:10.1016/s0378-5173(01)00676-7

Cited by 201 publications

(103 citation statements)

References 11 publications

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“…43,44 When liver becomes saturated, NPs are taken up by other organs, such as kidneys, bone marrow, and lungs instead, as indicated by our simulations on PAA-PEG and PAA NPs. In terms of mass, the doses of PAA-PEG and PAA NPs employed were 30-123-fold higher than those of gold and TiO 2 and in terms of NP number or total surface area, 1,300-2,400-fold higher (Table S12).…”

mentioning

confidence: 74%

Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

Carlander

Jolliet

et al. 2016

IJN

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To assess the potential toxicity of nanoparticles (NPs), information concerning their uptake and disposition (biokinetics) is essential. Experience with industrial chemicals and pharmaceutical drugs reveals that biokinetics can be described and predicted accurately by physiologically-based pharmacokinetic (PBPK) modeling. The nano PBPK models developed to date all concern a single type of NP. Our aim here was to extend a recent model for pegylated polyacrylamide NP in order to develop a more general PBPK model for nondegradable NPs injected intravenously into rats. The same model and physiological parameters were applied to pegylated polyacrylamide, uncoated polyacrylamide, gold, and titanium dioxide NPs, whereas NP-specific parameters were chosen on the basis of the best fit to the experimental time-courses of NP accumulation in various tissues. Our model describes the biokinetic behavior of all four types of NPs adequately, despite extensive differences in this behavior as well as in their physicochemical properties. In addition, this simulation demonstrated that the dose exerts a profound impact on the biokinetics, since saturation of the phagocytic cells at higher doses becomes a major limiting step. The fitted model parameters that were most dependent on NP type included the blood:tissue coefficients of permeability and the rate constant for phagocytic uptake. Since only four types of NPs with several differences in characteristics (dose, size, charge, shape, and surface properties) were used, the relationship between these characteristics and the NPdependent model parameters could not be elucidated and more experimental data are required in this context. In this connection, intravenous biodistribution studies with associated PBPK analyses would provide the most insight.

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confidence: 74%

Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

Carlander

Jolliet

et al. 2016

IJN

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“…Synthetic polymers and natural polymer materials are used to prepare nano-drug carriers. Examples of synthetic polymers include polyester-based aliphatic polyesters, aromatic polyesters, polycarbonates, polyanhydrides and polyamides (Panagi et al, 2001;Watnasirichaikul et al, 2002). Synthetic macromolecular materials can synthesize the desired product according to the specific need and can be modified to control the characteristics, yielding a product that is highly purified, non-toxic and readily degradable in vivo.…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vitro/in vivo evaluation of resveratrol-loaded carboxymethyl chitosan nanoparticles

Zhang

Wang

et al. 2014

Drug Delivery

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Resveratrol (RES) is natural polyphenol with a strong biological activity, but its disadvantages, such as poor water solubility, susceptibility to oxidative decomposition and rapid metabolism in the body, which substantially restricts in vivo bioavailability, need to be resolved. This study used carboxymethyl chitosan (CMCS) as a drug carrier and utilized emulsion cross-linking to prepare RES-loaded CMCS nanoparticles (RES-CMCSNPs). A single-factor experiment was performed to optimize the preparation of these particles; in vitro and in vivo characteristics were evaluated. Spherical RES-CMCSNPs were prepared under optimal conditions, in which average particle size, potential, drug loading and encapsulation efficiency were (155.3 ± 15.2) nm, (À10.28 ± 6.4) mV, (5.1 ± 0.8)% and (44.5 ± 2.2)%, respectively. FTIR, DSC and XRD showed that RES molecules were wrapped in the nanoparticles. In vitro DPPH radical scavenging abilities showed RES-CMCSNPs were better than RES raw powder. The nanoparticles improved the solubility of RES, thereby greatly improving the antioxidant activity of the drug. In vitro release experiments of RES and RES-CMCSNPs by simulating the human gastrointestinal tract were performed, in which RES-CMCSNPs rendered better releasing effects than raw RES. Raw RES and RES-CMCSNPs results were in line with those obtained for the single-chamber model for pharmacokinetic studies in rats. Compared with the bulk drugs, the RES-CMCSNPs exhibited increased in vivo absorption, prolonged duration of action and increased relative bioavailability by 3.516 times more than those of the raw RES. In addition, the residual chloroform is less than the ICH limit for class 2 solvents.

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“…Antibodies and complement proteins which can associate to foreign particles render microcapsules more attractive to phagocytes, thereby largely enhancing their clearance from the circulation system [35,36]. Since the mean size of our model NOMela-PLGA capsules presently lies between 1 and 3 µm (Figure 1), it must be expected that they would rapidly be cleared (within a few minutes [37]) from the blood by the reticuloendothelial system. According to Eq.s 1-4 NOMela is a NOdonor generating compound but it is not a direct NO releasing entity.…”

Section: Discussionmentioning

confidence: 99%

“…In order to avoid such undesirable effects, the properties of the capsules have to be improved for later in vivo use. So to solve the two problems (i) fast recognition by the RES and (ii) too large size, at first, removal of the capsules by macrophages of the reticuloendothelial system can be minimized by covering their surface with hydrophilic polymers such as covalently bound polyethyleneglycols [37][38][39]. Although principally, non-covalently bound polymers like Tetronic-908 have been shown to operate similarly in experimental systems [40] because of the replacement of the synthetic macromolecules by plasma proteins, such polymers are not suitable for in vivo applications due to their high toxicity.…”

Section: Discussionmentioning

confidence: 99%

Encapsulation of N-Nitroso-melatonin with Poly(lactide-co-glycolide)

Kirsch¹,

Korth²,

Fandrey³

et al. 2017

J Biotechnol Biomater

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N-Nitrosomelatonin (NOMela) is well known for its capabilities to transnitrosate nucleophiles such as thiols and ascorbate thereby generating nitric oxide (NO)-releasing compounds. Like molsidomine, NOMela is one of the few NO-releasing substrates not inducing nitrate tolerance and may be therefore highly suitable as NO-therapeutical. As the physical and chemical properties of NOMela do not allow its direct application (oral or intravascular) in animals/ humans, the encapsulation with biodegradable poly(lactide-co-glycolide) (PLGA) polymers was performed and NOreleasing kinetics were studied. NOMela could be successfully encapsulated in PLGA (NOMela-PLGA) with an efficiency of 85% thereby prolonging its half-life time in aqueous solution (e.g. in the cytoplasm of endothelial and smooth muscle cells) about 3-fold. In the presence of "activated hydroxy compounds" like vitamin C and thus under physiological conditions, NOMela-PLGA yielded two therapeutically relevant hormones, melatonin and nitric oxide, via reactions only known (until now) for unencapsulated, freely diffusing NOMela. Importantly, in the absence of any activated hydroxy compound the unwanted hydrolysis reaction of NOMela dominated, generating the non-functional nitrite (and not nitric oxide). These findings suggested that PLGA-encapsulated NOMela will be highly attractive as a novel NO-releasing drug lacking common side-effects of classical NO-releasing molecules such as glyceroltrinitrate.

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Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA–mPEG nanoparticles

Cited by 201 publications

References 11 publications

Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

Toward a general physiologically-based pharmacokinetic model for intravenously injected nanoparticles

Preparation and in vitro/in vivo evaluation of resveratrol-loaded carboxymethyl chitosan nanoparticles

Encapsulation of N-Nitroso-melatonin with Poly(lactide-co-glycolide)

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