Delivery Properties Research Articles

Impact of Pluronic F-127 on the Stability of Quercetin-Loaded Liposomes: Insights from DSC Preformulation Studies

The aim of the present study is to evaluate the stability of DMPC:Pluronic F-127 and DPPC:Pluronic F-127 liposomes, both with and without incorporated quercetin. Quercetin belongs to the class of flavonoids and has shown antioxidant, antiviral, anti-inflammatory, anti-cancer, and antimicrobial activities. Dynamic light scattering, electrophoretic light scattering, and differential scanning calorimetry (DSC) were utilized to investigate the cooperative behavior between liposomal components and its effect on stability. All formulations were stored at 4 °C and 25 °C and studied over 42 days. Furthermore, the interaction of the final formulations with serum proteins was assessed to evaluate the potential of Pluronic F-127 as a stabilizer in these liposomal nanosystems. This study highlights the impact of DSC in preformulation evaluations by correlating thermal behavior with quercetin incorporation and variations in size and the polydispersity index. According to the results, quercetin increased the fluidity and stability of liposomal nanosystems, while Pluronic F-127 was not sufficient for effective steric stabilization. Additionally, DSC thermograms revealed the integration of Pluronic F-127 into lipid membranes and showed phase separation in the DMPC nanosystem. In conclusion, the results indicate that the DPPC:Pluronic F-127:quercetin nanosystem exhibited the desired physicochemical and thermotropic properties for the effective delivery of quercetin for pharmaceutical purposes.

Preparation of DOX-TPP/HA-ss-OA Nanoparticles, Investigation of Drug Release Behavior In Vitro, and Evaluation of Anti-proliferative Activity In Vitro.

This study aimed to develop and characterize DOX-TPP/HA-ss-OA nanoparticles, utilizing the mitochondria-targeting prodrug doxorubicin-triphenylphosphine (DOXTPP) and a reduction-sensitive amphiphilic polymer, hyaluronic acid-disulfide-oleic acid (HAss- OA). The research focused on evaluating the drug release behavior of these nanoparticles under varying glutathione (GSH) concentrations and their anti-tumor activity in vitro. DOX-TPP/HA-ss-OA nanoparticles were prepared using probe ultrasound technology. The study examined the impact of different organic solvents on drug loading capacity and encapsulation efficiency to determine the optimal conditions. A single-factor experimental design was used to optimize the formulation process. Key parameters, including particle size and zeta potential, were measured to assess nanoparticle stability and performance. The dynamic dialysis method was employed to evaluate the reduction-sensitive drug release characteristics in media with different GSH concentrations. The MTT assay was used to analyze the growth-inhibitory effects of the nanoparticles on human breast cancer cells (MCF-7) and drug-resistant cells (MCF-7/ADR). The optimized preparation process for DOX-TPP/HA-ss-OA nanoparticles included a drug dosage of 2.0 mg, an oil-to-water volume ratio of 1:5, ultrasonic power of 500 W, and ultrasonic time of 15 minutes. The nanoparticles had an average particle size of 203.72 ± 2.30 nm and a zeta potential of 25.82 ± 0.58 mV, indicating favorable stability and effective drug delivery properties. The nanoparticles exhibited a slow, sustained release of DOX-TPP in pH 7.4 phosphate buffer solution (PBS) and accelerated release in high GSH concentrations, demonstrating reduction-responsive drug release. In vitro studies showed that DOX-TPP/HA-ss-OA nanoparticles significantly inhibited the proliferation of MCF-7 and MCF-7/ADR cells in a dosedependent manner, with enhanced efficacy compared to free DOX and other formulations. DOX-TPP/HA-ss-OA nanoparticles demonstrate excellent reduction sensitivity, effective tumor cell growth inhibition in vitro, and the ability to overcome drug resistance. Including particle size and zeta potential measurements supports their suitability as drug carriers, highlighting their potential for targeted cancer therapy and further development.

Stability and efficacy of pterostilbene nanoliposomes in cosmetic applications: A comprehensive study

Pterostilbene (PT), a lipid-soluble polyphenol known for its antioxidant, anticancer, and various other biological properties, holds potential as an active ingredient in cosmetics for its anti-wrinkle and skin-whitening effects. However, its application is limited by its low water solubility and poor penetration through the stratum corneum. To address these limitations, this study initially prepared Pterostilbene nanoliposomes (PT-NLPs) using a high shear-microjet homogenization treatment method, because of the distinctive hydrophilic and hydrophilic properties of the liposomes. The stability under different storage conditions of the PT-NLPs was evaluated by investigating the alterations of the particle size, PDI, Zeta potential and surface morphology, combined with the test results of Lumisizer stability analyzer. Finally, the comprehensive performance of PT-NLPs was evaluated through in vitro dermal and transdermal testing, human testing, and instrument testing. The results showed that the PT-NLPs treated by the high shear-microjet homogenisation method proposed in this paper possessed a 1.7-fold increase in the retention performance compared with the free PT solution, and no penetration occurred on the blood-brain barrier, indicating that PT-NLPs would not cause toxicity to the organism. The human efficacy evaluation found that the PT-NLPs whitening serum could improve skin dullness, brighten skin tone, and improve skin sensitivity after 14 days of use. The high shear-microjet homogenisation method proposed in this paper for the treatment of PT-NLPs improved the transdermal delivery properties of PT. The process has a broad application prospect in the fields of medicine and cosmetics.

Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study.

Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU). This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ). To induce colon cancer in rats, MNU (10 mg/Kg BW) was administrated intrarectally three times per week for four weeks. The treatment of Q (40 mg/Kg BW) or NDQ (40 mg/Kg BW) was given intraperitoneally twice a week for 6 weeks. Cancer progression of all cohorts was evaluated by performing body and colon weight measurements, which involved the following: ELISA assay-specific to metastatic marker matrix metalloprotein-9 (MMP-9), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 α (HIF1α), vascular endothelial growth factor, protein 53 (p53) and immunohistochemistry staining of Caspase-3 and Ki-67 proteins. Observation of cancer metastasis to the lung was also performed. NDQ significantly inhibited cancer aggressiveness by causing an increment in body weight gain and the growth rate-while reducing the colon weight compared to the K- group. Moreover, decreased levels of MMP-9, CEA, HIF-1α, and Ki67 and increased levels of p53 and Caspase-3 were more significant in the NDQ group than in the Q group. The lung tumor metastases in the NDQ group were fewer than in the K- group. NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

Enhancement of corrosion, biocompatibility and drug delivery properties of nitinol implants surface by Al-Zn-LDH nanohybrids

This study investigates the enhancement of drug delivery and corrosion resistance by incorporating dexamethasone sodium phosphate into aluminum-zinc layered double hydroxide (LDH) coated nickel-titanium alloys. The nickel-titanium samples were fabricated from titanium and nickel powders using spark plasma sintering (SPS) and cold press sintering (CPS), followed by electrophoretic deposition of LDH nanoparticles. This composite construction aims to utilize the biocompatibility and mechanical properties of nickel-titanium, combined with the controlled drug release and corrosion resistance properties of LDH coatings. Structural and microstructural characterizations were performed using X-ray diffraction and scanning electron microscopy. The results indicated that SPS samples exhibited superior microstructural homogeneity and corrosion resistance compared to CPS samples. Dexamethasone sodium phosphate was successfully intercalated into the LDH layers, as evidenced by an increase in layer spacing from 7.14 Å to 20.130 Å. The LDH-coated nickel-titanium with intercalated dexamethasone sodium phosphate demonstrated a 5 % lower drug release rate and significantly improved corrosion resistance compared to uncoated samples. Cell adhesion studies confirmed good biocompatibility between cells and the coated surface. This composite material shows promise for enhanced performance in biomedical applications, particularly in drug delivery and corrosion resistance.

From Cellulose Solutions to Aerogels and Xerogels: Controlling Properties for Drug Delivery.

A cheap and easy-to-recycle solvent, namely, aqueous NaOH with no additives, was used to dissolve cellulose and make cross-linker-free materials with varying porosity, testing them as drug delivery devices. Cellulose solutions were gelled, coagulated in a nonsolvent (water, ethanol), and dried either using supercritical CO2 (aerogels) or low-vacuum evaporation (named "xerogels"). Aerogels had densities of around 0.1 g/cm3 and specific surface areas (SSAs) of 200-400 m2/g. A significant influence of the first nonsolvent and drying mode on material properties was recorded: when the first nonsolvent was ethanol and low-vacuum drying was performed from ethanol, aerogel-like xerogels were obtained with densities of around 0.2 g/cm3 and SSAs of 200-260 m2/g. Other conditions (under evaporative drying) resulted in cellulose with much lower porosity and SSA. All materials were evaluated as drug delivery devices in simulated gastrointestinal fluids; theophylline was used as a model drug. Materials of high porosity exhibited shrinking and rapid drug release, whereas denser materials swelled and showed slower release. Two release mechanisms were suggested: diffusion through aqueous media in pores and diffusion through swollen pore walls. The results demonstrate a large spectrum of options for tuning the properties of porous cellulose materials for drug release applications.

Strong magnetic actuation system with enhanced field articulation through stacks of individually addressed coils

Miniaturization of medical tools promises to revolutionize surgery by reducing tissue trauma and accelerating recovery. Magnetic untethered devices, with their ability to access hard-to-reach areas without physical connections, emerge as potential candidates for such miniaturization. Despite the benefits, these miniature devices face challenges regarding force and torque outputs, restricting their ability to perform tasks requiring mechanical interactions such as tissue penetration and manipulation. To overcome magnetic actuation system-based force and torque limitations, this study proposes Variable Outer Radius Individually Addressable Coil Stacks (VORIACS), a novel magnetic actuation system optimized for high force output generation to magnetic devices within its workspace. The VORIACS marks significant improvements and breakthroughs in magnetic actuation within decimeter-scale workspace. The VORIACS is comprised of 12 coils that are optimized for 2D magnetic field generation under maximized power consumption of up to 12 kW. We implement six two-channel motor controllers, powered by six separate power supplies. Each of the twelve coils in the system is operated on its own motor-controller channel. This arrangement allows the system to exceed the magnetic forces and torques possible for single-coil versions of the same geometry. This study elaborates on optimizing, manufacturing, integrating, and demonstrating this system. Comparative analysis reveals that while a suboptimal, single-coil version of this system generates 0.31 N force (710 mT/m magnetic gradient magnitude), the VORIACS produces 1.673 N force (3834 mT/m magnetic gradient magnitude) on the same magnetic object placed 5 cm away from the coils. Moreover, the strong penetration force generated by VORIACS enables needle penetration to a mock gel that has the rigidity of liver tissue. In addition, we demonstrate the advantage of stacked coils with variable radii for magnetic field manipulability while maintaining the optimized force delivery property of the system, which improves control and could facilitate multi-tool manipulation. By enabling a fivefold increase in magnetic pulling force compared to its single-coil counterpart, VORICAS raises the potential penetration capabilities of untethered magnetic robotics in surgical procedures.

Addition of Ostrea rivularis polysaccharides in microneedle loaded with 3-acetylaconitine liposomes enhance analgesic activities and drug delivery properties.

3-Acetylaconitine (AAC) is a natural compound with strong anti-inflammatory and analgesic properties, but the severely narrow safety range limited its clinical application. Two dissolvable microneedle (MN) systems, AAC-ORP-MN and AAC-MN, loaded with AAC liposomes (AAC-Lips) either mixed with or without Ostrea rivularis polysaccharide (ORP) were developed. The size, zeta potential and encapsulation efficiency of AAC-Lips were 112.9 ± 0.5 nm, -31.3 ± 0.5 mV and 95.7 ± 1.2 %. AAC-ORP-MN demonstrated higher mechanical strength and faster initial drug release rate compared to AAC-MN. The results in the spared nerve injury (SNI) model showed that AAC-ORP-MN and AAC-MN both could significantly increase the mechanical pain threshold on the operated side of the rats, and gradually decrease the difference between the equilibrium pain thresholds of both feet, but AAC-ORP-MN showed a faster onset of action. In addition, AAC-ORP-MN significantly reduced inflammatory factors and improved pathological damage in the spinal cord better than AAC-MN, which might be due to the anti-inflammatory activity of ORP. Overall, the above results supported that AAC-ORP-MN showed promise as a clinical option for analgesia, which had anti-inflammatory and analgesic properties, meanwhile it could effectively deliver poorly water-soluble AAC and improve its safety and availability.

Photobiomodulation as Medicine: Low-Level Laser Therapy (LLLT) for Acute Tissue Injury or Sport Performance Recovery.

Background/Objectives: Low-level laser therapy (LLLT) has gained traction in sports and exercise medicine as a non-invasive therapeutic for preconditioning the body, exertion recovery, repair and injury rehabilitation. LLLT is hypothesized to modulate cellular metabolism, tissue microenvironment(s) and to decrease inflammation while posing few adverse risks. This review critically examines the evidence-base for LLLT effectiveness focusing on immediate care settings and acute/subacute applications (<6 months post-injury). Methods: A comprehensive literature search was conducted, prioritizing systematic reviews, meta-analyses and their primary research papers. Results: Findings are relevant to trainers and athletes as they manage a wide range of issues from superficial abrasions to deeper tissue concerns. LLLT parameters in the research literature include wide ranges. For body surface structures, studies show that LLLT holds promise in accelerating wound healing. In sport performance studies, LLLT is typically delivered pre-exercise and reveals beneficial effects on exertion recovery, improvements in muscle strength, endurance and reduced fatigue. Evidence is less convincing for acute, deep tissue injury models, where most studies do not report significant benefits for functional outcomes over conventional therapeutic modalities. Conclusions: Variability in LLLT delivery parameters and findings across studies underscores a need for clear treatment guidelines for the profession. Technical properties of laser light delivery to the body also differ materially from LED devices. Sport physiotherapists, team physicians, trainers and athletes should understand limitations in the current evidence-base informing photobiomodulation use in high-performance sport settings and weigh potential benefits versus shortcomings of LLLT use in the mentioned therapeutic contexts.

Synthesis of Urchin-Like Au@TiO2 Nano-Carriers as a Drug-Loading System Toward Cancer Treatment.

In recent years, improving the pharmaceutical properties of drug delivery for anti-cancer treatment has become increasingly important. This is necessary to address challenges related to absorption, distribution, and stability. One potential approach solution is to attach the drug to a carrier system, such as functional noble nanomaterials, in order to improve the control of drug release and stability. Core-satellite nanoparticles (CSN) with an anisotropic morphology have enormous potential for targeted drug delivery and cancer treatment because of their large surface area, exceptional stability, and biocompatibility. We used a simple seed-mediated approach to synthesize urchin-like gold nanoparticles (ULGNPs) with a high aspect ratio and a dense network of 49 nm-sized branches, using seed solution, silver nitrate, and ascorbic acid. The ULGNPs were synthesized without a surfactant and then encapsulated with thin layers of amorphous TiO2 (ULGNPs@TiO2), resulting in an average overall size of 136±15 nm with a 27.5 nm TiO2 layer. Doxorubicin (Dox) was chosen as a model drug to assess the distribution carrier ability of ULGNPs@TiO2 core-satellite nanoparticles. The results showed 86.5 % Dox loading and 72.3 % release capacity at pH 5. The anti-cancer ability of ULGNPs@TiO2-Dox was meticulously assessed using breast cancer MCF-7 cells in the WST-1 assay. The results revealed that ULGNPs@TiO2-Dox exhibited approximately 92 % toxicity in MCF-7 cells compared to the free Dox of 89.6 % at low concentrations (5 ppm). Based on the simulation results for loading ULGNPs@TiO2 with Dox, it was observed that a structure containing five layers of Au (111) with three fixed bottom layers and two relaxed top layers, in addition to six TiO2 (100) layers, was analyzed using Grimme's DFT-D3 dispersion corrections (Scheme 1). The density functional theory (DFT) adsorption energy (Eads) shows that the amorphous TiO2 increases the Dox loading activity of ULGNPs, with Eads=-3.85 eV, negatively higher than isolated ULGNPs (Eads=-2.87 eV) and TiO2 alone (Eads=-3.61 eV). This drug carrier design has the potential to revolutionize anti-cancer treatment.

Investigating the Size Effect of Metal-Organic Frameworks in Drug Delivery and Anticancer Properties.

Here, we show particle size-dependent therapeutic efficacy with a Zn-based metal-organic framework (MOF). The size of MOFs was tuned in specific ranges (∼100, 200, and 300 nm) built upon the manipulation of synthetic conditions. X-ray photoelectron spectroscopy, infrared, PXRD, and dynamic light scattering and scanning electron microscopy analyses were used to identify the synthesized structures. The various analyses revealed minimal changes in the molecular properties of these structures regardless of their size, confirming our hypothesis regarding the preservation of the identity of MOF nanoparticles despite size variation. The synthesized carriers undergo structure relative destruction in response to a weak acidic tumor microenvironment, and this relative degradation allows the release of the Nimesulide drug into the environment. Interestingly, anticancer studies resulting in SKBR3 (Human breast cancer cell) cells indicate that the different sizes resulted in various inhibition capacities against cancer cells. This work shows the importance of optimizing the geometry of the drug carrier, such as size and shape, to achieve the highest cellular uptake and therapeutic performance. Besides, theoretical studies were carried out using B3LYP/6-31G (d,p) and density functional theory methods to more consider the drug adsorption mechanism.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

Bifunctional sludge-derived redox carbon dots with photoelectron storage and delivery properties for ammonia production by photosensitized Shewanella oneidensis MR-1

Combining the light-harvesting capabilities of photosensitizers with microbial catalysis shows great potential in solar-driven biomanufacturing. However, little information is available about the effects of photosensitizers on the photoelectron transport during the dissimilatory nitrate reduction to ammonium (DNRA) process. Herein, redox carbon dots (CDs-500) were prepared from sludge via the pyrolysis-Fenton reaction and then used to construct a photosynthetic system with Shewanella oneidensis MR-1. The MR-1/CDs-500 photosynthetic system showed a 5.9-fold increase in ammonia production (4.9 mmol(NH3)·g−1(protein)·h−1) with a high selectivity of 94.0 %. The photoelectrons were found to be stored in CDs-500 and transferred into the cells. During the inward electron transport, the intracellular CDs-500 could be used as the direct photoelectron transfer stations between outer membrane cytochrome c and DNRA-related enzymes without the involvement of CymA and MtrA. This work provides a new method for converting waste into functional catalysts and increases solar-driven NH3 production to a greater extent.

Drug Binding to Partially Unfolded Serum Albumin: Insights into Nonsteroidal Anti-Inflammatory Drug Naproxen-BSA Interactions from Spectroscopic and MD Simulation Studies.

Understanding the binding details of a small-molecule drug to a protein in its partially unfolded state is important for drug delivery as it provides insight into the overall drug-binding ability of the protein, even when the majority of binding pockets in its unfolded state are impaired. The interaction of partially unfolded proteins with drugs remains poorly understood due to a lack of structural information on proteins in their partially unfolded states. Here, we studied the interaction between serum albumin (bovine serum albumin (BSA) as a model system), an abundant protein in blood serum that is an effective carrier for numerous known drugs, and a nonsteroidal anti-inflammatory drug (NSAID) naproxen (NPS) using various spectroscopic and computational methods. Molecular dynamics simulations starting from the drug-unbound state and performed at physiological and higher temperatures revealed novel hydrophobic sites on the BSA surface. We analyzed the BSA-NPS interaction in the presence and absence of the cationic organized assembly CTAB and two oligosaccharides (β-CD and 2-HP-β-CD) at different excitation wavelengths. The solvation dynamics of BSA under NPS-bound conditions became ∼4.6% faster. Oligosaccharides were found to increase the solubility of NPS by providing a hydrophobic environment for the formation of inclusion complexes through host-guest interactions. These findings provide a comprehensive overview and uncover the binding model and mechanism of interaction of NPS with BSA, revealing hydrophobic and electrostatic interactions and hydrogen bonds required for BSA to bind NPS at these noncanonical sites. The molecular-level understanding of the binding mechanism of commonly used NSAIDs like NPS with partially unfolded BSA will be useful in designing pharmaceutically important molecules with efficient loading and delivery properties.

Characterizing Extracellular Vesicles Generated from the Integra CELLine Culture System and Their Endocytic Pathways for Intracellular Drug Delivery.

Extracellular vesicles (EVs) have attracted great attention as promising intracellular drug delivery carriers. While the endocytic pathways of small EVs (sEVs, <200 nm) have been reported, there is limited understanding of large EVs (lEVs, >200 nm), despite their potential applications for drug delivery. Additionally, the low yield of EVs during isolation remains a major challenge in their application. Herein, we aimed to compare the endocytic pathways of sEVs and lEVs using MIA PaCa-2 pancreatic cancer cell-derived EVs as models and to explore the efficiency of their production. The cellular uptake of EVs by MIA PaCa-2 cells was assessed and the pathways were investigated with the aid of endocytic inhibitors. The yield and protein content of sEVs and lEVs from the Integra CELLine culture system and the conventional flasks were compared. Our findings revealed that both sEVs and lEVs produced by the Integra CELLine system entered their parental cells via multiple routes, including caveolin-mediated endocytosis, clathrin-mediated endocytosis, and actin-dependent phagocytosis or macropinocytosis. Notably, caveolin- and clathrin-mediated endocytosis were more prominent in the uptake of sEVs, while actin-dependent phagocytosis and macropinocytosis were significant for both sEVs and lEVs. Compared with conventional flasks, the Integra CELLine system demonstrated a 9-fold increase in sEVs yield and a 6.5-fold increase in lEVs yield, along with 3- to 4-fold higher protein content per 1010 EVs. Given that different endocytic pathways led to distinct intracellular trafficking routes, this study highlights the unique potentials of sEVs and lEVs for intracellular cargo delivery. The Integra CELLine proves to be a highly productive and cost-effective system for generating EVs with favourable properties for drug delivery.

Development of dual drug loaded-hydrogel scaffold combining microfluidics and coaxial 3D-printing for intravitreal implantation

Treating diabetic retinopathy (DR) effectively is challenging, aiming for high efficacy with minimal discomfort. While intravitreal injection is the current standard, it has several disadvantages. Implantable systems offer an alternative, less invasive, with long-lasting effects drug delivery system (DDS). The current study aims to develop a soft, minimally invasive, biodegradable, and bioadhesive material-based hydrogel scaffold to prevent common issues with implants. A grid-shaped scaffold was created using coaxial 3D printing (3DP) to extrude two bioinks in a single filament. The scaffold comprises an inner core of curcumin-loaded liposomes (CUR-LPs) that prepared by microfluidics (MFs) embedded in a hydrogel of hydroxyethyl cellulose (HEC), and an outer layer of hyaluronic acid-chitosan matrix with free resveratrol (RSV), delivering two Sirt1 agonists synergistically activating Sirt1 downregulated in DR. Optimized liposomes, prepared via MFs, exhibit suitable properties for retinal delivery in terms of size (<200 nm), polydispersity index (PDI) (<0.3), neutral zeta potential (ZP), encapsulation efficiency (∼97 %), and stability up to 4 weeks. Mechanical studies confirm scaffold elasticity for easy implantation. The release profiles show sustained release of both molecules, with different patterns related to different localization of the molecules. RSV released initially after 30 min with a total release more than 90 % at 336 h. CUR release starts after 24 h with only 4.78 % of CUR released before and gradually released thanks to its internal localization in the scaffold. Liposomes and hydrogels can generate dual drug-loaded 3D structures with sustained release. Microscopic analysis confirms optimal distribution of liposomes within the hydrogel scaffold. The latter resulted compatible in vitro with human retinal microvascular endothelial cells up to 72 h of exposition. The hydrogel scaffold, composed of hyaluronic acid and chitosan, shows promise for prolonged treatment and minimally invasive surgery.

Fabrication and characteristics of new quaternized chitosan nanocapsules loaded with thymol or thyme essential oil as effective SARS-CoV-2 inhibitors.

This research explores the potential of encapsulating thyme essential oil (TEO) and thymol (TH) into quaternized chitosan nanocapsules to combat SARS-CoV-2. Initially, the bioactive materials, TH and TEO, were extracted from Thymus vulgaris and then structurally and phytochemically characterized by spectral and GC-MS analyses. Meanwhile, O-quaternized ultrasonic-mediated deacetylated chitosan (QUCS) was successfully synthesized and characterized. Lastly, nanobiocomposites (NBCs; NBC1 and NBC2) were fabricated using QUCS as a scaffold to encapsulate either TEO or TH, with the mediation of Tween 80. By encapsulating these bioactive materials, we aim to enhance their efficacy and targeted delivery, bioavailability, stability, and anti-COVID properties. The new NBCs were structurally, morphologically, and physically characterized. Incorporating TEO or TH into QUCS significantly increased ZP values to ±53.1 mV for NBC1 and ±48.2 mV for NBC2, indicating superior colloidal stability. Interestingly, Tween 80-QUCS provided outstanding packing and release performance, with entrapment efficiency (EE) and loading capacity (LC) values of 98.2% and 3.7% for NBC1 and 83.7% and 1.9% for NBC2. The findings of in vitro antiviral studies not only highlight the potential of these nanobiocomposites as potential candidates for anti-COVID therapies but also underscore their selectivity in targeting SARS-CoV-2.

Curcumin nanoparticles in heat stroke management

ObjectiveThe exacerbation of extreme high-temperature events due to global climate change poses a significant challenge to public health, particularly impacting the central nervous system through heat stroke. This study aims to develop Poly(amidoamine) (PAMAM) nanoparticles loaded with curcumin (PAMAM@Cur) to enhance its therapeutic efficacy in hypothalamic neural damage in a heat stroke model and explore its potential mechanisms.MethodsCurcumin (Cur) was encapsulated into PAMAM nanoparticles through a hydrophobic interaction method, and various techniques were employed to characterize their physicochemical properties. A heat stroke mouse model was established to monitor body temperature and serum biochemical parameters, conduct behavioral assessments, histological examinations, and biochemical analyses. Transcriptomic and proteomic analyses were performed to investigate the therapeutic mechanisms of PAMAM@Cur, validated in an N2a cell model.ResultsPAMAM@Cur demonstrated good stability, photostability, cell compatibility, significant blood–brain barrier (BBB) penetration capability, and effective accumulation in the brain. PAMAM@Cur markedly improved behavioral performance and neural cell structural integrity in heat stroke mice, alleviated inflammatory responses, with superior therapeutic effects compared to Cur or PAMAM alone. Multi-omics analysis revealed that PAMAM@Cur regulated antioxidant defense genes and iron death-related genes, particularly upregulating the PCBP2 protein, stabilizing SLC7A11 and GPX4 mRNA, and reducing iron-dependent cell death.ConclusionBy enhancing the drug delivery properties of Cur and modulating molecular pathways relevant to disease treatment, PAMAM@Cur significantly enhances the therapeutic effects against hypothalamic neural damage induced by heat stroke, showcasing the potential of nanotechnology in improving traditional drug efficacy and providing new strategies for future clinical applications.SignificanceThis study highlights the outlook of nanotechnology in treating neurological disorders caused by heat stroke, offering a novel therapeutic approach with potential clinical applications.Graphical abstract

Optimization and evaluation of a chitosan-coated PLGA nanocarrier for mucosal delivery of Porphyromonas gingivalis antigens

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively.The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages.The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.

A Multicomponent Microneedle Patch for the Delivery of Meloxicam for Veterinary Applications.

This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. In vitro imaging confirms the microneedle patch penetrates the pig's ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, in vitro drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, in vivo studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.