“…Notably, the particle size of the carriers was kept nearly monodispersed and < 100 nm. Biodistribution of larger colloidal carriers could be of use in the treatment of infections involving the RES, whereas brain and tumour delivery remains at lower level [39]. Drug delivery outside the RES can be achieved by adjusting the colloidal carrier size, coating with different non-ionic surfactants or attachment of targeting vector molecules to the surface of carriers [40].…”
Section: Drug Delivery Systems Increase Therapeutic Effect Of Nucleosmentioning
Nanogels are colloidal microgel carriers that have been introduced recently as a prospective drug delivery system for nucleotide therapeutics. The crosslinked protonated polymer network of nanogels binds oppositely charged drug molecules, encapsulating them into submicron particles with a coreshell structure. The nanogel network also provides a suitable template for chemical engineering, surface modification and vectorisation. This review reveals recent attempts to develop novel drug formulations of nanogels with antiviral and antiproliferative nucleoside analogs in the active form of 5′-triphosphates; discusses structural approaches to the optimisation of nanogel properties, and; discusses the development of targeted nanogel drug formulations for systemic administration. Notably, nanogels can improve the CNS penetration of nucleoside analogs that are otherwise restricted from passing across the blood-brain barrier. The latest findings reviewed here demonstrate an efficient intracellular release of nucleoside analogs, encouraging further applications of nanogel carriers for targeted drug delivery.
“…Notably, the particle size of the carriers was kept nearly monodispersed and < 100 nm. Biodistribution of larger colloidal carriers could be of use in the treatment of infections involving the RES, whereas brain and tumour delivery remains at lower level [39]. Drug delivery outside the RES can be achieved by adjusting the colloidal carrier size, coating with different non-ionic surfactants or attachment of targeting vector molecules to the surface of carriers [40].…”
Section: Drug Delivery Systems Increase Therapeutic Effect Of Nucleosmentioning
Nanogels are colloidal microgel carriers that have been introduced recently as a prospective drug delivery system for nucleotide therapeutics. The crosslinked protonated polymer network of nanogels binds oppositely charged drug molecules, encapsulating them into submicron particles with a coreshell structure. The nanogel network also provides a suitable template for chemical engineering, surface modification and vectorisation. This review reveals recent attempts to develop novel drug formulations of nanogels with antiviral and antiproliferative nucleoside analogs in the active form of 5′-triphosphates; discusses structural approaches to the optimisation of nanogel properties, and; discusses the development of targeted nanogel drug formulations for systemic administration. Notably, nanogels can improve the CNS penetration of nucleoside analogs that are otherwise restricted from passing across the blood-brain barrier. The latest findings reviewed here demonstrate an efficient intracellular release of nucleoside analogs, encouraging further applications of nanogel carriers for targeted drug delivery.
“…11,12 As an evidence of this desorption, blood pharmacokinetic profiles of drugs adsorbed onto polysorbate 80-coated PBCA nanoparticles administered intravenously were actually similar to free solutions, 25,34,35 and not at all typical of drugs associated to nonstealth colloidal drug carriers. 21,22,23,36 Therefore, as an alternative to the brain uptake of nanoparticles, we hypothesized a nanoparticle-induced nonspecific BBB permeabilization. 11 It has been known for a long time that polysorbate 80 causes BBB disturbance at intravenous systemic doses as low as 3 mg/kg 37 (25-100 mg/kg polysorbate 80 doses were used in brain targeting experiments 7,25,27 ).…”
Section: General Considerationsmentioning
confidence: 99%
“…17 Lacking stealth properties, poly(alkylcyanoacrylate) nanoparticles administered intravenously are rapidly cleared from the blood stream by the monuclear phagocyte system (MPS) and mainly accumulate in liver and spleen, 18 -20 together with the entrapped compounds. [21][22][23] Only pegylated polyalkylcyanoacrylate nanoparticles have lower MPS uptake and prolonged blood circulation in vivo. 24 Brain delivery with PBCA nanoparticles Adsorbed onto polysorbate 80-coated PBCA nanoparticles administered intravenously compounds with poor brain diffusion as diverse as doxorubicin, 25,26 loperamide, 27 tubocurarine, 28 the hexapeptide dalargin 6,7 were successfully delivered to the brain, where they induced a pharmacological effect (for review, see Kreuter 29 ).…”
Summary: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50 -300 nm generally). They cannot freely diffuse through the bloodbrain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)-polylactide or poly(lactide-co-glycolide) (mPEG-PLA/ PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.
“…Simeonova et al [ 28 ] found that polybutylcyanoacrylate nanoparticles loaded with spin-labelled nitrosourea were localized in the lungs and blood of Lewis lung carcinoma-bearing mice. [ 28 ] Based on this finding, the blood kinetics data of the spin-labelled nitrosourea, registered by EPR ( Figure 2 (A)) and 99m Tc-SLENU in blood of healthy mice after labelling with radio-isotope ( Figure 2 (B)), were investigated, respectively. Figure 2.…”
Recently, a new class of in vitro and ex vivo radiotracers/radioprotectors, the nitroxyl-labelled agent 1-ethyl-1-nitroso–3-[4-(2,2,6,6–tetramethylpiperidine-1-oxyl)]-urea (SLENU), has been discovered. Our previous investigations demonstrated that SLENU is a low-molecular-weight stable free radical which is freely membrane permeable, easily crosses the blood brain barrier and exhibited in/ex vivo the lowest general toxicity and higher anticancer activity against some experimental tumour models. Further investigation was aimed to develop a 99mTc-labelled SLENU (97%) as a chelator and evaluate its labelling efficiency and potential use as a tumour seeking agent and for early diagnosis. Tissue biodistribution of 99mTc-SLENU was determined in normal mice at 1, 2 and 24 h (n = 4/time interval, route of administration i.v.). The distribution data were compared using male albino non-inbred mice and electron paramagnetic resonance investigation. The imaging characteristics of 99mTc-SLENU conjugate examined in BALB/c mice grafted with Ehrlich Ascitis tumour in the thigh of hind leg demonstrated major accumulation of the radiotracer in the organs and tumour. Planar images and auto-radiograms confirmed that the tumours could be visualized clearly with 99mTc-SLENU. Blood kinetic study of radio-conjugate showed a bi-exponential pattern, as well as quick reduced duration in the blood circulation. This study establishes nitroxyls as a general class of new spin-labelled diagnostic markers that reduce the negative lateral effects of radiotherapy and drug damages, and are appropriate for tumour-localization.
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