Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application

Network Pharmacology and Molecular Docking Reveal Anti-Asthmatic Potential of Zephyranthes rosea Lindl. in an Ovalbumin-Induced Asthma Model

Background: This study aimed to evaluate the anti-inflammatory effects of a Zephyranthes rosea in an ovalbumin-induced asthma model. Methods: Allergic asthma was induced in mice via intraperitoneal injection, followed by intranasal ovalbumin challenge. Methanolic extract of Z. rosea bulb was orally administered to asthmatic mice for 14 days. Hematological parameters for bronchoalveolar lavage fluid (BALF) and blood were analyzed. The mRNA expression levels of interleukins and transforming growth factor beta (TGF-β1) in lung tissues were determined using reverse transcriptase–polymerase chain reaction (RT–PCR). Network pharmacology analysis was used to find possible Z. rosea targets. After building a protein–protein interaction network to find hub genes, GO and KEGG enrichment analyses were carried out to determine the potential mechanism. In silico analysis was performed by Molecular Operating Environment. Results: GC-MS analysis of Z. rosea extract detected major classes of phytochemicals. Hematological parameters in blood and BALF from Z. rosea extract-treated animals were significantly reduced in a dose-dependent fashion. Histopathology revealed that Z. rosea bulb had an ameliorative effect on lung tissues. Moreover, treatment with Z. rosea bulb extract significantly restored the normal levels of IL-4, IL-6, IL-1β, IL-10, IL-13, and TGF-β1 in allergic asthmatic mice compared to the diseased group. In silico analysis, particularly of the binding affinities of Z. rosea bulb phytoconstituents for IL6, AKT1, and Src, supported in vivo results. Conclusions: These findings indicated that Z. rosea bulb extract significantly ameliorates cellular and molecular biomarkers of bronchial inflammation and could be a potential candidate for treating allergic asthma

Quercetin and Kaempferol as Multi-Targeting Antidiabetic Agents against Mouse Model of Chemically Induced Type 2 Diabetes

Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affinities of both compounds towards multiple antidiabetic targets were explored using pharmacokinetic and docking software (AutoDock Vina 1.1.2). Our findings showed that quercetin and kaempferol obey Lipinski’s rule of five and exhibit desirable ADMET (absorption, distribution, metabolism excretion, and toxicity) profiles. Both compounds showed higher binding affinities towards C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase-4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium–glucose co-transporter-1 (SGLT-1) compared to metformin (the positive control). Both quercetin and kaempferol inhibited α-amylase activity (in vitro) up to 20.30 ± 0.49 and 37.43 ± 0.42%, respectively. Their oral supplementation significantly reduced blood glucose levels (p p p p < 0.0001) with no effect on the viability of Vero cell line (non-cancer). In conclusion, quercetin and kaempferol demonstrated higher binding affinities towards multiple targets than metformin. In vitro and in vivo antidiabetic potential along with the anticancer activities of both compounds suggest promise for further development in diabetes management. The combination of both drugs did not show a synergistic effect, possibly due to their same target on the receptors

Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.</div

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.</jats:p

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = −29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = −18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.</jats:p