Anti-inflammatory and anti-arthritic activities of glycosylated flavonoids from syzygium jambos in edematogenic agent-induced paw edema in mice

Two glycosylated flavonoids, the quercetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside and myricetin-3-O-β-d-xylofuranosyl-(1 → 2)-α-l-rhamnopyranoside, were isolated from the CH2Cl2/MeOH fraction of Syzygium jambos (L.) Alston, Myrtaceae. The structures of these compounds were elucidated by spectroscopic means. The cytotoxicity of the compounds was evaluated against the RAW 264.7 cell lines by the lactate dehydrogenase assay. All analyzed compounds were less cytotoxic than the positive control (actinomycin D, CC50 = 0.008 μM). The anti-inflammatory and anti-arthritic activities were evaluated by measuring inflammatory parameters in murine models. The two glycosylated flavonoids inhibited the production of tumor necrosis factor-α in RAW 264.7 cell line with IC50 of 1.68 and 1.11 μM, respectively. In addition, all flavonoids decreased the levels of tumor necrosis factor-α, C-reactive protein, and fibrinogen at a dose of 5 mg/kg in murine modelsThis work was supported by the National Herbarium of Bolivia and the Fundación de la Universidad Autónoma de Madrid (FUAM

Micro- and Nano-Systems Developed for Tolcapone in Parkinson’s Disease

To date there is no cure for Parkinson’s disease (PD), a devastating neurodegenerative disorder with levodopa being the cornerstone of its treatment. In early PD, levodopa provides a smooth clinical response, but after long-term therapy many patients develop motor complications. Tolcapone (TC) is an effective adjunct in the treatment of PD but has a short elimination half-life. In our work, two new controlled delivery systems of TC consisting of biodegradable PLGA 502 (poly (D,L-lactide-co-glycolide acid) microparticles (MPs) and nanoparticles (NPs) were developed and characterized. Formulations MP-TC4 and NP-TC3 were selected for animal testing. Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Formulation NP-TC3, prepared with 10 mg of TC and 50 mg of PLGA 502, exhibited mean EE of 56.69%, particle size of 182 nm, and controlled the release of TC for 8 days. Daily i.p. (intraperitoneal) doses of rotenone (RT, 2 mg/kg) were given to Wistar rats to induce neurodegeneration. Once established, animals received TC in saline (3 mg/kg/day) or encapsulated within formulations MP-TC4 (amount of MPs equivalent to 3 mg/kg/day TC every 14 days) and NP-TC3 (amount of NPs equivalent to 3 mg/kg/day TC every 3 days). Brain analyses of Nissl-staining, GFAP (glial fibrillary acidic protein), and TH (tyrosine hydroxylase) immunohistochemistry as well as behavioral testing (catalepsy, akinesia, swim test) showed that the best formulation was NP-TC3, which was able to revert PD-like symptoms of neurodegeneration in the animal model assayed

Nanotechnology-based drug delivery of ropinirole for Parkinson’s disease

A new drug delivery system is developed for ropinirole (RP) for the treatment of Parkinson’s disease (PD) consisting of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The formulation selected was prepared with 8 mg RP and 50 mg PLGA 502. This formulation exhibited mean encapsulation efficiency of 74.8 ± 8.2%, mean particle size lower than 155 nm, the zeta potential of −14.25 ± 0.43 mV and zero-order in vitro release of RP (14.13 ± 0.17 μg/h/10 mg NPs) for 5 d. Daily doses of the neurotoxin rotenone (2 mg/kg) given i.p. to male Wistar rats induced neuronal and behavioral changes similar to those of PD. Once neurodegeneration was established (15 d) animals received RP in saline (1 mg/kg/d for 35 d) or encapsulated within PLGA NPs (amount of NPs equivalent to 1 mg/kg/d RP every 3 d for 35 d). Brain histology and immunochemistry (Nissl-staining, glial fibrillary acidic protein and tyrosine hydroxylase immunohistochemistry) and behavioral testing (catalepsy, akinesia, rotarod and swim test) showed that RP-loaded PLGA NPs were able to revert PD-like symptoms of neurodegeneration in the animal model assayed

Anti-melanogenic and Anti-inflammatory Activities of Hibiscus sabdariffa

Hibiscus sabdariffa L., Malvaceae, is traditionally cultivated for its stem, leaves, calyces, and seeds as all parts have industrial, medicinal, and cosmetic applications. Likewise, there are many works on the biological properties of the aqueous extract of H. sabdariffa due to its high content of polyphenolic compounds. Using the Folin-Ciocalteu method, the total polyphenol content of an aqueous extract of a sample from Guatemala was found to be 15.97 ± 0.49 mg GAE/g. The presence of ten phenolic acids, ten flavonoids, and two anthocyanins was determined by 1 H NMR analysis. The anti-melanogenic activity assay of the aqueous extract showed inhibition of the tyrosinase activity (IC50 3.53 ± 0.16 μg/ml) and inhibition of the melanin production (IC50 3.90 ± 0.17 μg/ml) in the B16F10 cell line. Finally, the aqueous extract showed an inhibition of NO production with an IC50 of 4.72 ± 0.34 μg/ml and 3.62 ± 0.36 μg/ml in the RAW 264.7 and B16F10 cell lines, respectively. Our results allowed us to identify those polyphenolic compounds present in the aqueous extract of H. sabdariffa whose synergic effect increases the anti-melanogenic and anti-inflammatory properties of the aqueous extract

Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo

Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood–brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain-targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of cannabidiol to LNCs outperformed by 6-fold the enhancement observed for the G-Technology (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases). As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases.Ministerio de Educación, Cultura y Deporte(España)Universidad Complutense de MadridBanco SantanderDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu

Micro- and Nano-Systems Developed for Tolcapone in Parkinson’s Disease

To date there is no cure for Parkinson’s disease (PD), a devastating neurodegenerative disorder with levodopa being the cornerstone of its treatment. In early PD, levodopa provides a smooth clinical response, but after long-term therapy many patients develop motor complications. Tolcapone (TC) is an effective adjunct in the treatment of PD but has a short elimination half-life. In our work, two new controlled delivery systems of TC consisting of biodegradable PLGA 502 (poly (D,L-lactide-co-glycolide acid) microparticles (MPs) and nanoparticles (NPs) were developed and characterized. Formulations MP-TC4 and NP-TC3 were selected for animal testing. Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Formulation NP-TC3, prepared with 10 mg of TC and 50 mg of PLGA 502, exhibited mean EE of 56.69%, particle size of 182 nm, and controlled the release of TC for 8 days. Daily i.p. (intraperitoneal) doses of rotenone (RT, 2 mg/kg) were given to Wistar rats to induce neurodegeneration. Once established, animals received TC in saline (3 mg/kg/day) or encapsulated within formulations MP-TC4 (amount of MPs equivalent to 3 mg/kg/day TC every 14 days) and NP-TC3 (amount of NPs equivalent to 3 mg/kg/day TC every 3 days). Brain analyses of Nissl-staining, GFAP (glial fibrillary acidic protein), and TH (tyrosine hydroxylase) immunohistochemistry as well as behavioral testing (catalepsy, akinesia, swim test) showed that the best formulation was NP-TC3, which was able to revert PD-like symptoms of neurodegeneration in the animal model assayedComplutense University of Madrid(UCM) research group "Formulation and Bioavailability of New Drugs"Depto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaInstituto Universitario de Farmacia IndustrialTRUEpu

Controlled Release of Highly Hydrophilic Drugs from Novel Poly(Magnesium Acrylate) Matrix Tablets

The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two di_erent crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel e_ectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its di_usion through the gel layer (Fickian di_usion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.Universidad Complutense de MadridDepto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaTRUEpu