12 research outputs found
BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB.
Microglia-mediated neuroinflammatory responses are inevitable and important pathological processes in several kinds of disorder of the central nervous system (CNS). Therefore, alleviating activated microglia-induced inflammatory process might be a valuable therapeutic approach to neuroinflammation-related diseases. In the present study, we investigated BHDPC, a novel neuroprotectant discovered in our previous study that had anti-inflammatory effects under neuroinflammatory conditions. First, we found that BHDPC could inhibit neuroinflammatory responses and promote microglial M2 phenotype polarization in both lipopolysaccharide (LPS)-activated BV-2 microglia l cells. Furthermore, BHDPC provided protective actions against neuroinflammation-induced neurotoxicity in HT22 mouse hippocampal cells co-cultured with activated BV-2 microglia. Further experiments demonstrated that BHDPC could suppress LPS-induced activation of transcription factor nuclear factor kappa B (NF-κB) via interfering with the degradation of the inhibitor of kappa B (IκB) and phosphorylation of IκB, the IκB kinase (IKK). Moreover, we also found that BHDPC could induce phosphorylation of cAMP-dependent protein kinase A (PKA) and cAMP-response element-binding protein (CREB) in BV-2 microglial cells. Also, using the PKA-specific inhibitor, we found that BHDPC-induced CREB phosphorylation was dependent on PKA, which also contributed to BHDPC-mediated anti-inflammation and neuroprotection
Preparation and characterization of pelletized solid dispersion of resveratrol with mesoporous silica microparticles to improve dissolution by fluid-bed coating techniques
With hydrophilic surface and high surface area, porous silica has been applied to load insoluble drugs. Compared to solvent equilibrium method, resveratrol (RES)–mesoporous silica microparticles (MSM) solid dispersion prepared by fluid bed demonstrated higher drug loading and more complete dissolution. Pore volume and diameter have more remarkable effects than surface area to the drug loading and in vitro dissolution profiles. RES–polyethylene glycol solid dispersion with high drug loading showed fast but incomplete dissolution due to the recrystallization. The combination of fluid bed and MSM was an effective strategy to improve drug loading as well as dissolution for poorly water-soluble drugs
Extracellular vesicles: a rising star for therapeutics and drug delivery
Abstract Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood–brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs. Graphical Abstrac
Innovative Strategies for Hair Regrowth and Skin Visualization
Today, about 50% of men and 15–30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin’s barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin’s structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future
Ultrasmall Coordination Polymers for Alleviating ROS-Mediated Inflammatory and Realizing Neuroprotection against Parkinson’s Disease
Parkinson’s disease (PD) is the second most common neurodegenerative disease globally, and there is currently no effective treatment for this condition. Excessive accumulation of reactive oxygen species (ROS) and neuroinflammation are major contributors to PD pathogenesis. Herein, ultrasmall nanoscale coordination polymers (NCPs) coordinated by ferric ions and natural product curcumin (Cur) were exploited, showing efficient neuroprotection by scavenging excessive radicals and suppressing neuroinflammation. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model, such ultrasmall Fe-Cur NCPs with prolonged blood circulation and BBB traversing capability could effectively alleviate oxidative stress, mitochondrial dysfunction, and inflammatory condition in the midbrain and striatum to reduce PD symptoms. Thus, this study puts forth a unique type of therapeutics-based NCPs that could be used for safe and efficient treatment of PD with potential in clinical translation
Oral Delivery of a Nanocrystal Formulation of Schisantherin A with Improved Bioavailability and Brain Delivery for the Treatment of Parkinson’s Disease
Schisantherin A (SA)
is a promising anti-Parkinsonism Chinese herbal
medicine but with poor water solubility and challenges to be delivered
to the brain. We formulated SA as nanocrystals (SA-NC), aiming to
improve its solubility and pharmacokinetic profile and thus provide
a potential therapeutic agent for the treatment of Parkinson’s
disease (PD). The rod-shaped SA-NC had a particle size of ∼160
nm with 33.3% drug loading, and the nanocrystals exhibited a fast
dissolution rate <i>in vitro</i>. The intact drug nanocrystals
could be internalized into Madin-Darby canine kidney (MDCK) cells,
which were followed by rapid intracellular release, and most of the
drug was transported to the basolateral side in its soluble form.
Following oral administration of the SA-NC or an SA suspension, the
accumulated concentration of the SA-NC in the plasma and brain was
considerably higher than that observed for the SA suspension, but
the drug targeting efficiency was similar. The SA-NC significantly
reversed the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
dopaminergic (DA) neuronal loss and locomotion deficiency in zebrafish,
as well as the 1-methyl-4-phenylpyridinium ion (MPP<sup>+</sup>)-induced
damage of neuronal cell culture model. Further Western blot analysis
demonstrated that the stronger neuroprotective effect of SA-NC may
be partially mediated by the activation of the protein kinase B (Akt)/glycogen
synthase kinase-3β (Gsk3β) pathway. Taken together, these
data provide solid evidence that the nanocrystal formulation has the
potential to improve the bioavailability and brain concentration of
this Biopharmaceutics Classification System (BCS) class II compound,
SA, for the treatment of PD
Multidomain Oriented Particle Chains Based on Spatial Electric Field and Their Optical Application
Schisantherin A Attenuates Neuroinflammation in Activated Microglia: Role of Nrf2 Activation Through ERK Phosphorylation
Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity
Overexpression
of the drug efflux transporter multidrug resistance-associated
protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier
compromises the oral delivery of drugs to the circulation system and
brain in the treatment of Parkinson’s disease (PD). In this
study, we aim to develop small-sized Pluronic P85/F68 micelles loaded
with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate
related mechanism, as well as the anti-Parkinsonian efficacy. Spherical
and sustained-release B-MCs have a mean particle size of 40.61 nm,
a low critical micelle concentration (CMC) of 5.01 × 10<sup>–3</sup> mg/mL with an encapsulation efficiency of 95.47% and a drug loading
of 7.07%. In comparison with the free baicalein, the cellular uptake
and apparent permeability coefficient (<i>P</i><sub>app</sub>) of B-MCs were significantly enhanced (<i>p</i> < 0.01).
Fluorescence resonance energy transfer (FRET) analysis indicated that
micelles carrying the hydrophobic fluorophores were internalized intact,
followed by a rapid release of fluorophores inside the cells, and
then the released free fluorophores were transported across the cell
monolayers to the basolateral side. Further study on the MRP2 inhibitory
effect showed that B-MCs could reverse the MRP2-mediated efflux of
baicalein via interfering with the structure and function of mitochondria,
i.e., reducing mitochondrial membrane potential and intracellular
ATP level and influencing the respiration chain of mitochondria. In
addition, B-MCs exerted strong neuroprotective effects on zebrafish
model of PD. In summary, Pluronic P85/F68 micelles could be considered
as a promising drug delivery system to reverse MRP2-mediated efflux
and improve the bioactivity of this MRP2 substrate, baicalein, for
the treatment of PD
Small-Sized mPEG–PLGA Nanoparticles of Schisantherin A with Sustained Release for Enhanced Brain Uptake and Anti-Parkinsonian Activity
Schisantherin A (SA)
is a promising anti-Parkinsonism natural product.
However, its poor water solubility and rapid serum clearance impose
significant barriers to delivery of SA to the brain. This work aimed
to develop SA in a nanoparticle formulation that extended SA circulation
in the bloodstream and consequently an increased brain uptake and
thus to be potentially efficacious for the treatment of Parkinson’s
disease (PD). Spherical SA nanoparticles with a mean particle size
of 70 nm were prepared by encapsulating SA into methoxy polyÂ(ethylene
glycol)-<i>block</i>-polyÂ(d,l)-lactic-<i>co</i>-glycolic acid (mPEG–PLGA) nanoparticles (SA-NPs)
with an encapsulation efficiency of ∼91% and drug loading of
∼28%. The in vitro release of the SA-NPs lasted for 48 h with
a sustained-release pattern. Using the Madin–Darby canine kidney
(MDCK) cell model, the results showed that first intact nanoparticles
carrying hydrophobic dyes were internalized into cells, then the dyes
were slowly released within the cells, and last both nanoparticles
and free dyes were externalized to the basolateral side of the cell
monolayer. Fluorescence resonance energy transfer (FRET) imaging in
zebrafish suggested that nanoparticles were gradually dissociated
in vivo with time, and nanoparticles maintained intact in the intestine
and brain at 2 h post-treatment. When SA-NPs were orally administrated
to rats, much higher <i>C</i><sub>max</sub> and <i>AUC</i><sub><i>0‑t</i></sub> were observed
in the plasma than those of the SA suspension. Furthermore, brain
delivery of SA was much more effective with SA-NPs than with SA suspension.
In addition, the SA-NPs exerted strong neuroprotective effects in
zebrafish and cell culture models of PD. The protective effect was
partially mediated by the activation of the protein kinase B (Akt)/glycogen
synthase kinase-3β (Gsk3β) pathway. In summary, this study
provides evidence that small-sized mPEG–PLGA nanoparticles
may improve cross-barrier transportation, oral bioavailability, brain
uptake, and bioactivity of this Biopharmaceutics Classification System
(BCS) Class II compound, SA