Fabrication of mesoporous silica nanoparticles for releasable delivery of licorice polysaccharide at the acne site in topical application.

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.

ß-Glucan-A promising immunocyte-targeting drug delivery vehicle: Superiority, applications and future prospects.

Drug delivery technologies that could convert promising therapeutics into successful therapies have been under broad research for many years. Recently, ß-glucans, natural-occurring polysaccharides extracted from many organism species such as yeast, fungi and bacteria, have attracted increasing attention to serve as drug delivery carriers. With their unique structure and innate immunocompetence, ß-glucans are considered as promising carriers for targeting delivery especially when applied in the vaccine construction and oral administration of therapeutic agents. In this review, we focus on three types of ß-glucans applied in the drug delivery system including yeast ß-glucan, Schizophyllan and curdlan, highlighting the benefits of ß-glucan based delivery system. We summarize how ß-glucans as delivery vehicles have aided various therapeutics ranging from macromolecules including proteins, peptides and nucleic acids to small molecular drugs to reach desired cells or organs in terms of loading strategies. We also outline the challenges and future directions for developing the next generation of ß-glucan based delivery systems.

The study of galactomannans with different molecular weights and their ability to form microparticles suitable for pulmonary delivery.

The influence of locust bean gum (LBG) galactomannans (GMs) molecular weight (Mw) to assemble microparticulate systems was evaluated, and carriers for deep lung delivery were developed. A commercial batch of LBG with a mannose/galactose (M/G) ratio of 2.4 (batch 1) was used to study the influence of different microwave partial acid hydrolysis conditions on carbohydrate composition, glycosidic linkages, and aqueous solutions viscosity. The microwave treatment did not affect the composition, presenting 4-Man (36-42 %), 4,6-Man (27-35 %), and T-Gal (24-25 %) as the main glycosidic linkages. Depolymerization led to a viscosity reduction (≤0.005 Pa·s) with no major impact on polysaccharide debranching. The structural composition of the LBG galactomannans were further elucidated with sequence-specific proteins using carbohydrate microarray technologies. A second batch of LBG (M/G 3.3) was used to study the impact of GMs with different Mw on microparticle assembling, characteristics, and insulin release kinetics. The low-Mw GMs microparticles led to a faster release (20 min) than the higher-Mw (40 min) ones, impacting the release kinetics. All microparticles exhibited a safety profile to cells of the respiratory tract. However, only the higher-Mw GMs allowed the assembly of microparticles with sizes suitable for this type of administration.

Red Blood Cell-Hitchhiking Delivery of Simvastatin to Relieve Acute Respiratory Distress Syndrome.

Purpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects. Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs). Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug's circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug's efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions. Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM's poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.

Bioavailability Enhancement of BCS Class II Raloxifene Hydrochloride by Inclusion Complex and Solid Dispersion Techniques.

OBJECTIVE: Raloxifene hydrochloride (RLX) is used extensively in the treatment of osteoporosis, only 2% of RLX's bioavailability remains after a significant first pass metabolism. Besides coming from BCS class II, RLX is not very soluble in water. Thus, the goal of the current study was to improve RLX solubility by creating an inclusion complex using ß cyclodextrin (ß-CD) as a carrier and solid dispersion with Poloxamer 407. METHODS: Inclusion complex and solid dispersion were made using a variety of techniques, including kneading, co-precipitation, and physical mixing and solid dispersion using different drug to carrier ratios (1:1, 1:2 and 1:3). RESULTS: Inclusion complex made using the co-precipitation method had shown 9-fold improvements in water solubility when compared with plain RLX. In order to assess the optimized complex's compatibility, thermal analysis, and crystallinity, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy were used. The XRD and DSC study's results indicated that RLX changed from a crystalline to an amorphous state. IC-6 exhibits effective water solubility based on the outcome. However, upon comparison of the two techniques, the ß-CD complexation method shown an impressive rise in drug solubility when compared to solid dispersion.

Bioinspired cellular membrane-derived vesicles for mRNA delivery.

The rapid advancement of mRNA as vaccines and therapeutic agents in the biomedical field has sparked hope in the fight against untreatable diseases. Successful clinical application of mRNA therapeutics largely depends on the carriers. Recently, a new and exciting focus has emerged on natural cell-derived vesicles. These nanovesicles offer many functions, including enhanced drug delivery capabilities and immune evasion, thereby presenting a unique and promising platform for the effective and safe delivery of mRNA therapeutics. In this study, we summarize the characteristics and properties of biomimetic delivery systems for mRNA therapeutics. In particular, we discuss the unique features of cellular membrane-derived vesicles (CDVs) and the combination of synthetic nanovesicles with CDVs.

Curcumin loaded ß-cyclodextrin-magnetic graphene oxide nanoparticles decorated with folic acid receptors as a new theranostic agent to improve prostate cancer treatment.

This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), ß-cyclodextrin (ß-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@ß-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.

Functional polymeric DNA nanostructure-decorated cellulose nanocrystals for targeted and stimuli-responsive drug delivery.

Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy.

The carrier function and inhibition effect on benign prostatic hyperplasia of a glucan from Epimedium brevicornu Maxim.

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.

Hyaluronic Acid-Bilirubin Nanoparticles as a Tumor Microenvironment Reactive Oxygen Species-Responsive Nanomedicine for Targeted Cancer Therapy.

Introduction: The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties. Methods & Results: DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects. Conclusion: These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.

Crafting Docetaxel-Loaded Albumin Nanoparticles Through a Novel Thermal-Driven Self-Assembly/Microfluidic Combination Technology: Formulation, Process Optimization, Stability, and Bioavailability.

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.

Application of Quality by Design in the Development of Hydrogen Sulfide Donor Loaded Polymeric Microparticles.

Hydrogen sulfide (H2S) is a multifaceted gasotransmitter molecule which has potential applications in many pathological conditions including in lowering intraocular pressure and providing retinal neuroprotection. However, its unique physicochemical properties pose several challenges for developing its efficient and safe delivery method system. This study aims to overcome challenges related to H2S toxicity, gaseous nature, and narrow therapeutic concentrations range by developing polymeric microparticles to sustain the release of H2S for an extended period. Various formulation parameters and their interactions are quantitatively identified using Quality-by-Design (QbD) approach to optimize the microparticle-based H2S donor (HSD) delivery system. Microparticles were prepared using a solvent-evaporation coacervation process by using polycaprolactone (PCL), soy lecithin, dichloromethane, Na2S.9H2O, and silicone oil as polymer, surfactant, solvent, HSD, and dispersion medium, respectively. The microparticles were characterized for size, size distribution, entrapment efficiency, and H2S release profile. A Main Effects Screening (MES) and a Response Surface Design (RSD) model-based Box-Behnken Design (BBD) was developed to establish the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs) qualitatively and quantitatively. The MES model identified polymer to drug ratio and dispersion medium quantity as significant CPPs among others, while the RSD model established their quantitative relationship. Finally, the target product performance was validated by comparing predicted and experimental outcomes. The QbD approach helped in achieving overall desired microparticle characteristics with fewer trials and provided a mathematical relationship between the CPPs and the CQAs useful for further manipulation and optimization of release profile up to at least 30 days.

Navigating Skin Delivery Horizon: An Innovative Approach in Pioneering Surface Modification of Ultradeformable Vesicles.

In the dynamic landscape of pharmaceutical advancements, the strategic application of active pharmaceutical ingredients to the skin through topical and transdermal routes has emerged as a compelling avenue for therapeutic interventions. This non-invasive approach has garnered considerable attention in recent decades, with numerous attempts yielding approaches and demonstrating substantial clinical potential. However, the formidable barrier function of the skin, mainly the confinement of drugs on the upper layers of the stratum corneum, poses a substantial hurdle, impeding successful drug delivery via this route. Ultradeformable vesicles/carriers (UDVs), positioned within the expansive realm of nanomedicine, have emerged as a promising tool for developing advanced dermal and transdermal therapies. The current review focuses on improving the passive dermal and transdermal targeting capacity by integrating functionalization groups by strategic surface modification of drug-loaded UDV nanocarriers. The present review discusses the details of case studies of different surface-modified UDVs with their bonding strategies and covers the recent patents and clinical trials. The design of surface modifications holds promise for overcoming existing challenges in drug delivery by marking a significant leap forward in the field of pharmaceutical sciences.

Composite Microgels Loaded with Doxorubicin-Conjugated Amine-Functionalized Zinc Ferrite Nanoparticles for Stimuli-Responsive Sustained Drug Release.

Purpose: The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development. Methods: We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 oC, with the drug release kinetics being analyzed using various models. Results: The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion. Conclusion: Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.

Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.

Multivariate Analysis of Solubility Parameters for Drug-Polymer Miscibility Assessment in Preparing Raloxifene Hydrochloride Amorphous Solid Dispersions.

The success of obtaining solid dispersions for solubility improvement invariably depends on the miscibility of the drug and polymeric carriers. This study aimed to categorize and select polymeric carriers via the classical group contribution method using the multivariate analysis of the calculated solubility parameter of RX-HCl. The total, partial, and derivate parameters for RX-HCl were calculated. The data were compared with the results of excipients (N = 36), and a hierarchical clustering analysis was further performed. Solid dispersions of selected polymers in different drug loads were produced using solvent casting and characterized via X-ray diffraction, infrared spectroscopy and scanning electron microscopy. RX-HCl presented a Hansen solubility parameter (HSP) of 23.52 MPa1/2. The exploratory analysis of HSP and relative energy difference (RED) elicited a classification for miscible (n = 11), partially miscible (n = 15), and immiscible (n = 10) combinations. The experimental validation followed by a principal component regression exhibited a significant correlation between the crystallinity reduction and calculated parameters, whereas the spectroscopic evaluation highlighted the hydrogen-bonding contribution towards amorphization. The systematic approach presented a high discrimination ability, contributing to optimal excipient selection for the obtention of solid solutions of RX-HCl.

Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives.

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H2O}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO3)2·3H2O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H2OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.

Dual drug-loaded polymeric mixed micelles for ovarian cancer: Approach to enhanced therapeutic efficacy of albendazole and paclitaxel.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.

Controlled Quercetin Release by Fluorescent Mesoporous Nanocarriers for Effective Anti-Adipogenesis.

Introduction: Quercetin (QUER), a flavonoid abundant in fruits and vegetables, is emerging as a promising alternative therapeutic agent for obesity treatment due to its antioxidant and anti-adipogenic properties. However, the clinical application of QUER is limited by its poor solubility, low bioavailability, and potential toxicity at high doses. To address these challenges, this study aims to develop an advanced drug delivery system using fluorescent mesoporous silica nanoparticles (FMSNs) coated with polydopamine (PDA) for the efficient and sustained delivery of QUER to inhibit adipogenesis. Methods: The research included the synthesis of PDA-coated FMSNs for encapsulation of QUER, characterization of their mesoporous structures, and systematic investigation of the release behavior of QUER. The DPPH assay was used to evaluate the sustained radical scavenging potential. Concentration-dependent effects on 3T3-L1 cell proliferation, cellular uptake and adipogenesis inhibition were investigated. Results: PDA-coated FMSNs exhibited well-aligned mesoporous structures. The DPPH assay confirmed the sustained radical scavenging potential, with FMSNs-QUER@PDA showing 53.92 ± 3.48% inhibition at 72 h, which was higher than FMSNs-QUER (44.66 ± 0.57%) and free QUER (43.37 ± 5.04%). Concentration-dependent effects on 3T3-L1 cells highlighted the enhanced efficacy of PDA-coated FMSNs for cellular uptake, with a 1.5-fold increase compared to uncoated FMSNs. Adipogenesis inhibition was also improved, with relative lipid accumulation of 44.6 ± 4.6%, 37.3 ± 4.6%, and 36.5 ± 7.3% at 2.5, 5, and 10 µM QUER concentrations, respectively. Conclusion: The study successfully developed a tailored drug delivery system, emphasizing sustained QUER release and enhanced therapeutic effects. FMSNs, especially when coated with PDA, exhibit promising properties for efficient QUER delivery, providing a comprehensive approach that integrates advanced drug delivery technology and therapeutic efficacy.

Solid lipid nanoparticle: A potent vehicle of the kaempferol for brain delivery through the blood-brain barrier in the focal cerebral ischemic rat.

Kaempferol is major flavonoid present in Convolvulus pluricaulis. This phytochemical protects the brain against oxidative stress, neuro-inflammation, neurotoxicity, neurodegeneration and cerebral ischemia induced neuronal destruction. Kaempferol is poorly water soluble. Our study proved that solid lipid nanoparticles (SLNs) were efficient carrier of kaempferol through blood-brain barrier (BBB). Kaempferol was incorporated into SLNs prepared from stearic acid with polysorbate 80 by the process of ultrasonication. Mean particle size and zeta potential of kaempferol loaded solid lipid nanoparticles (K-SLNs) were 451.2 nm and -15.0 mV. Atomic force microscopy showed that K-SLNs were spherical in shape. Fourier transformed infrared microscopy (FTIR) showed that both stearic acid and kaempferol were present in K-SLNs. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed that the matrices of K-SLNs were in untidy crystalline state. Entraptment efficiency of K-SLNs was 84.92%. In-vitro drug release percentage was 93.24%. Kaempferol loaded solid lipid nanoparticles (K-SLNs) showed controlled release profile. In-vitro uptake study showed significant efficiency of K-SLNs to cross blood-brain barrier (BBB). After oral administration into the focal cerebral ischemic rat, accumulation of fluorescent labeled K-SLNs was observed in the brain cortex which confirmed its penetrability into the brain. It significantly decreased the neurological deficit, infarct volume and level of reactive oxygen species (ROS) and decreased the level of pro-inflammatory mediators like NF-κB and p-STAT3. Damaged neurons and brain texture were improved. This study indicated increased bioavailability of kaempferol into the brain tissue through SLNs formulation.