Radiolabeled multi-layered coated gold nanoparticles as potential biocompatible PET/SPECT tracers.

The demand for tailored, disease-adapted, and easily accessible radiopharmaceuticals is one of the most persistent challenges in nuclear imaging precision medicine. The aim of this work was to develop two multimodal radiotracers applicable for both SPECT and PET techniques, which consist of a gold nanoparticle core, a shell involved in radioisotope entrapment, peripherally placed targeting molecules, and biocompatibilizing polymeric sequences. Shell decoration with glucosamine units located in sterically hindered molecular environments is expected to result in nanoparticle accumulation in high-glucose-consuming areas. Gold cores were synthesized using the Turkevich method, followed by citrate substitution with linear PEG α,ω-functionalized with thiol and amine groups. The free amine groups facilitated the binding of branched polyethyleneimine through an epoxy ring-opening reaction by using PEG α,ω-diglycidyl ether as a linker. Afterwards, the glucose-PEG-epoxy prepolymer has been grafted onto the surface of AuPEG-PEI conjugates. Finally, the AuPEG-PEI-GA conjugates were radiolabeled with 99mTc or 68Ga. Instant thin-layer chromatography was used to evaluate the radiolabeling yield. The biocompatibility of non-labeled and 99mTc or 68Ga labeled nanoparticles was assessed on normal fibroblasts. The 99mTc complexes remained stable for over 22 hours, while the 68Ga containing ones revealed a slight decrease in stability after 1 hour.

Intracerebroventricular Coadministration of Protoxin-II and Trace Elements in Rats Enhances the Analgesic Effect of the 1.7 Voltage-Gate Sodium Channel Blocker.

Pain continues to be a global unmet medical need, and the current recommendations for its management require a constant exploration of new drugs that target multiple pain mechanisms, with an improved safety profile and increased treatment adherence. Currently, the enriched distribution and localization within nociceptors of the selective channel blockers and the critical role played by sodium channels in neuronal excitability nominate isoforms as specific targets to generate innovative compounds. In the present report, we verified the hypothesis that coadministration of Protoxin-II, a selective sodium channel inhibitor, and trace elements has direct and improved antinociceptive effects. Groups of seven Wistar rats were treated intracerebroventricularly with a combination of MgCl2, CdCl2, and ZnCl2 and Protoxin-II, respectively, and with Protoxin-II alone (positive) or saline (negative) for controls. Evaluations were performed by nociception assay. Coadministration of these drugs caused an increase in the maximum possible effect of up to 40% as compared with the control groups. Our findings indicate that selective channel blockers continue to be an important nociception target and that the use of trace elements may provide simple but effective means of control over sodium channel blockers' risks, potentially lowering the necessary analgesic doses, thus improving the efficacy and safety profile.

Medicinal Plants of the Family Lamiaceae in Pain Therapy: A Review.

Recently, numerous side effects of synthetic drugs have lead to using medicinal plants as a reliable source of new therapy. Pain is a global public health problem with a high impact on life quality and a huge economic implication, becoming one of the most important enemies in modern medicine. The medicinal use of plants as analgesic or antinociceptive drugs in traditional therapy is estimated to be about 80% of the world population. The Lamiaceae family, one of the most important herbal families, incorporates a wide variety of plants with biological and medical applications. In this study, the analgesic activity, possible active compounds of Lamiaceae genus, and also the possible mechanism of actions of these plants are presented. The data highlighted in this review paper provide valuable scientific information for the specific implications of Lamiaceae plants in pain modulation that might be used for isolation of potentially active compounds from some of these medicinal plants in future and formulation of commercial therapeutic agents.

Formulation and evaluation of cefuroxim loaded submicron particles for ophthalmic delivery.

Chitosan gelatin particles could be the ideal candidate for intraocular drug delivery due to their desirable properties. Double crosslinking in double emulsion has been used as an original and reliable method for particles preparation and their morphology has been optimized considering the main synthesis parameters such as polymers ratio, crosslinker amount, stirring speed, tensioactive amount and ionic crosslinking time, respectively. The particles have been analyzed for their physical-chemical properties (swelling degree, drug loading and release capacity, surface characteristics, etc.), the enzymatic degradation properties along with in vivo ocular investigations (ocular biodistribution, in vivo drug release). In the present study cefuroxim was used as a model drug, which is generally used in the prophylaxis of postoperative endophthalmitis following cataract surgery after intraocular administration. The present study proved that the dimensions and the physical-chemical properties of the particles can be modulated (by varying the preparation parameters) to facilitate the administration, the biodistribution and the drug release in the specific segment of the eye. This experimental study demonstrated also the ability of fluorescent nanoparticles to penetrate ocular tissues close to the administration site (intravitreal injection) and especially their tendency to migrate deep in the retina at time intervals of 72 h.

Cardiovascular Risk Factors in Chronic Inflammatory Rheumatic Diseases: Modern Assessment and Diagnosis.

The current view is that systemic inflammation, which is specific to all chronic inflammatory rheumatic diseases (CIRD), accelerates atherogenesis; this hypothesis is supported by the high cardiovascular (CV) morbidity and mortality rates and the high prevalence of all atherosclerosis stages and complications in CIRD patients. The assessment of traditional CV risk factors underestimates the actual risk in patients with CIRD. A comprehensive evaluation and follow-up of both traditional and non-traditional CV risk factors, as well as the correct classification of risk reduction categories are necessary. Imaging techniques (e.g. carotid intima-media thickness and flow-mediated vasodilation) can be used for the early diagnosis of endothelial dysfunction. Immunologic and metabolic markers (anti-cyclic citrullinated peptide (CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, proinflammatory cytokines, TH0/TH1 lymphocytes and homocysteine) may be involved in the atherosclerotic disease development specific to CIRD. A modern therapeutic approach should include the early diagnosis of endothelial dysfunction and atherosclerosis, treatment of CIRD, specific medication designed to control atherosclerosis, changes in patient lifestyle and periodic follow-ups. The assessment and diagnosis of traditional and non-traditional CV risk factors, followed by aggressive prevention and therapy, are necessary to achieve efficient control over the inflammation, immunologic and metabolic disorders specific to CIRD.

Common trace elements alleviate pain in an experimental mouse model.

Trace elements represent a group of essential metals or metaloids necessary for life, present in minute amounts. Analgesic adjuvants can enhance the effect of other pain drugs or be used for pain control themselves. Previous studies on the effects of trace elements on nociception and their potential use as analgesic adjuvants have yielded conflicting results. In this study, we tested the hypothesis that three vital trace elements (Zn²âº, Mg²âº, Cu²âº) have direct antinociceptive effects. Groups of eight Swiss mice were intraperitoneally (i.p) injected with incremental concentrations of Zn²âº sulfate (0.5, 2.0 mg/kg), Zn²âº citrate (0.125, 0.5 mg/kg), Mg²âº chloride (37.5, 75, 150 mg/kg), Cu²âº chloride (0.5, 1.0, 2.0 mg/kg), and Cu²âº sulfate (0.5, 1.0 mg/kg) or saline (control). Evaluations were made by hot plate (HP) and tail flick (TF) tests for central antinociceptive effect, writhing test (WT) for visceral antinociceptive effect, and activity cage (AC) test for spontaneous behavior. Zn²âº induced pain inhibition in HP/TF tests (up to 17%) and WT (up to 25%), with no significant differences among the salts used. Mg²âº salts induced pain inhibition for all performed tests (up to 85% in WT). Cu²âº salts showed antinociceptive effects for HP/TF (up to 28.6%) and WT (57.28%). Only Mg²âº and Cu²âº salts have displayed significant effects in AC (Mg²âº anxiolytic/depressant effect; Cu²âº anxiolytic effect). We interpret these data to mean that all tested trace elements induced antinociceptive effects in central and visceral pain tests. Our data indicate the potential use of these cheap adjuvants in pain therapy.