Drug Encapsulation Research Articles

Optimization of Mesoporous Silica Nanoparticles of Silymarin through Statistical Design Experiment and Surface Modification by APTES

ABSTRACT: The major goal of this study was to create surface-modified mesoporous silica nanoparticles (MSN) of Silymarin, which has a short half-life and requires regular dosing due to first-pass metabolism. MSN was prepared by cost effective Sol-Gel method, functionalized by (3-Aminoprpyl) triethoxysilane (3-APTES). Evaluated and compared the Silymarin-loaded MSN and APTES functionalized MSN for drug loading, in-vitro dissolution, particle size, surface morphology, surface area, pore size and volume. The percent drug loading and encapsulation efficiency of APTES-functionalized MSN were found to be 92.50±0.72 % percent and 93.20±0.13 %, respectively, which showed a higher value in APTES-functionalized MSN as compared to Silymarin-loaded MSN. Drug release of APTES-functionalized MSN was 92.15 0.03%, which was more as compared to silymarin-loaded MSN. XRD showed that after functionalization silymarin changed from crystalline to amorphous form. SEM indicates that MSN was formed in a spherical shape with particle size of 196.7nm. The BET analysis proved that the nanoparticles had a larger surface area, which was reduced after drug loading and functionalization. Also, the pore size was increased and the pore volume was reduced after functionalization, indicating the incorporation of silymarin. The results suggested that the functionalization might successfully increase adsorption capacity, larger surface area, and increased encapsulation. Mesoporous silica nanoparticles also showed a greater impact on dissolution.

Investigation of the Impact of Manufacturing Methods on Protein-Based Long-Acting Injectable Formulations: A Comparative Assessment for Microfluidics vs. Conventional Methods.

Therefore, rhCCL22-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles were prepared by conventional homogenization and microfluidics methods. The resulting microparticles were analyzed comparatively, focusing on critical quality attributes such as microparticle size, size distribution, morphology, drug encapsulation efficiency, release kinetics, and batch-to-batch variations in relation to the manufacturing method. Our results demonstrated that the conventional method resulted in microparticles with denser surface porosity and wider size distribution as opposed to microparticles prepared by the microfluidics method, which could contribute to a significant difference in the drug-release kinetics. Additionally, our findings indicated minimal variation within batches for the microparticles prepared by the microfluidics method. Overall, this study highlights the comparative assessment of several critical quality attributes and batch variations associated with the manufacturing methods of protein-loaded microparticles which is crucial for ensuring consistency in efficacy, regulatory compliance, and quality control in the drug formulation manufacturing process.

Rod-shaped mesoporous silica nanoparticles reduce bufalin cardiotoxicity and inhibit colon cancer by blocking lipophagy

BackgroundBufalin (BA) is a potent traditional Chinese medicine derived from toad venom. It has shown significant antitumor activity, but its use is limited by cardiotoxicity, which necessitates innovative delivery methods, such as rod-shaped mesoporous silica nanoparticles (rMSNs). rMSNs have been extensively employed for reducing drug toxicity and for controlled or targeted drug delivery in tumor therapy. However, their potential in delivering BA has not been completely elucidated. Therefore, in this study, BA-loaded rMSNs (BA-rMSNs) were developed to investigate their potential and mechanism in impairing colon cancer cells.MethodsrMSNs were developed via the sol‒gel method. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the rMSN in loading BA. The antiproliferative activities of the BA-rMSNs were investigated via 5-ethynyl-2’-deoxyuridine and CCK-8. To evaluate cell death, Annexin V-APC/PI apoptotic and calcein-AM/PI double staining were performed. Western blotting, oil red O staining, and Nile red solution were employed to determine the ability of BA-rMSNs to regulate lipophagy.ResultsThe diameter of the BA-rMSNs was approximately 60 nm. In vitro studies demonstrated that BA-rMSNs markedly inhibited HCT 116 and HT-29 cell proliferation and induced cell death. In vivo studies revealed that BA-rMSNs reduced BA-mediated cardiotoxicity and enhanced BA tumor targeting. Mechanistic studies revealed that BA-rMSNs blocked lipophagy.ConclusionsrMSNs reduced BA-mediated cardiotoxicity and impaired the growth of colon cancer cells. Mechanistically, antitumor activity depends on lipophagy.

Synthesis of lipid‐modified copolymers based on caprolactone via enzymatic ring‐opening polymerization and click chemistry and evaluation of their potential as vehicles in drug delivery

AbstractThis research focuses on the application of click chemistry to the synthesis of amphiphilic lipidic copolymers with a target number of oleyl, cholesteryl, and linoleic pendant groups. The synthesis was performed using a two‐step approach. In the first step, copolymerization of ε‐caprolactone (CL) and α‐azido‐caprolactone (N3CL) was carried out using enzymatic ring‐opening polymerization (eROP) catalyzed by Candida Antarctica lipase B (CALB). This resulted in copolymers with an average molecular weight of 9.53 kDa, each containing approximately seven azide groups per chain. Subsequently, click chemistry was utilized to react P(N3CL‐co‐CL) copolymers with propargylated lipidic compounds, achieving azide group consumption higher than 88%. These lipidic copolymers exhibited reduced crystallinity, as evidenced by their lower melting enthalpy values. In addition, these materials were evaluated for the fabrication of nanostructured vehicles for curcumin (Cur@NP) using the solvent emulsion‐evaporation methodology. The lipidic copolymers demonstrated enhanced encapsulation efficiencies and drug loading capacities of 25 and 12%, respectively, tunable particle sizes in the range of 260–420 nm, and controlled release profiles over 30 h. Cur@NPs demonstrated notable antioxidant and antibacterial activities, particularly against Gram‐positive bacteria such as Staphylococcus aureus, achieving efficiencies close to 50%.

Innovative Proniosomal Formulation of Cilnidipine, Optimization and InDepth Characterization.

This study aims to enhance the solubility and bioavailability of cilnidipine as a dual L/N-type calcium channel blocker for hypertension using proniosomes. Proniosomes are dry powders that turn into niosomes when they come into contact with water, improving drug encapsulation and stability. Different concentrations of Span-60, cholesterol, and sorbitol were tested in the Box-Behnken design. The entrapment efficiency, particle size, zeta potential, thermal characteristics, crystalline structure and in-vitro drug release were evaluated for 17 formulations. Entrance effectivity was highest in F3 at 71.83%, while a controlled released rate of over 85.28% was observed within 12 hours. The median particle size showed a moderate stability of -11.2 mV with zeta potentials indicating this fact (902.7 nm). When, cilnidipine was inserted into proniosome systems, considerable changes occurred both thermally and crystallinity-wise according to DSC as well as XRD measurements were taken during an experiment where various mathematical models showed first-order kinetics dominated among other processes involved in drug release along Higuchi’s Equation.

Optimizing locally delivered periodontitis therapy: Development of chitosan‐hydroxyapatite‐encapsulated drug via electrospraying

AbstractThis study presents the development of an optimized drug delivery system for periodontitis treatment utilizing chitosan‐hydroxyapatite nanoparticles. Employing the electrospraying technique, researchers encapsulated the antibiotic amoxicillin within chitosan‐hydroxyapatite composite matrices while varying the concentrations of chitosan and hydroxyapatite nanoparticles. The resulting microparticles displayed sizes ranging from 276 to 386 μm. Characterization of the produced drug encapsulations indicated that higher concentrations of chitosan and hydroxyapatite resulted in the formation of larger particles with rougher surfaces, increased mechanical strength, and enhanced thermal stability. Notably, nanoindentation analysis revealed an increase in hardness from 0.21 to 0.35 GPa, and in elastic modulus from 5.32 to 8.72 GPa with escalating chitosan and hydroxyapatite content, meeting or surpassing requirements for load‐bearing regenerative biomaterials. In vitro drug release assessments exhibited sustained amoxicillin release over 24 h, predominantly through diffusion and dissolution mechanisms. Formulations with lower polymer and mineral content showcased elevated release rates, with the F1 encapsulation (0.5% chitosan, 0.2% HAP) achieving a cumulative release of 78.3 ± 3.2% in contrast to 65.1 ± 2.7% for the F5 formulation (2.5% chitosan, 1% HAP). These encapsulations selectively modulated the overproduction of proinflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, in gingival fibroblasts and osteoblasts without compromising cell viability. An artificial neural network (ANN) model accurately forecasted the material properties and biological performance of the formulations based on their compositional variations, yielding correlation coefficients exceeding 0.97. This computational platform offers a virtual screening tool for refining regenerative and drug delivery therapies. The developed chitosan‐hydroxyapatite microparticulate system demonstrates promising potential for prolonged treatment of periodontitis through controlled antibiotic delivery, improved mechanical properties, and targeted regulation of the inflammatory response.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.

Hyaluronic Acid in Nanopharmaceuticals: An Overview.

Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability to interact with various therapeutic agents, improving the delivery and efficacy of drugs. HA-based nanoparticles, including solid lipid nanoparticles, and polymeric nanogels, offer controlled release, enhanced stability, and targeted delivery of therapeutic agents. These innovations significantly improve therapeutic outcomes and reduce side effects, making HA an essential tool in modern medicine. In general, HA-modified liposomes enhance drug encapsulation and targeting, while HA-modified solid lipid nanoparticles (SLNs) provide a solid lipid core for drug encapsulation, offering controlled release and stability. This article provides an overview of the potential applications and recent advancements of HA in nanopharmaceuticals, emphasizing its significant impact on the evolving field of targeted drug delivery and advanced therapeutic strategies. By delving into the unique properties of HA and its compatibility with various therapeutic agents, this review underscores the promising potential of HA in revolutionizing nanopharmaceuticals.

PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells.

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64nm) and a more negative zeta potential (-36.94 ± 0.32mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.

Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs.

While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material's slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.

Biocompatible Glycopolymer-PLA Amphiphilic Hybrid Block Copolymers with Unique Self-Assembly, Uptake, and Degradation Properties.

The self-assembly of Janus-type amphiphilic hybrid block copolymers composed of hydrophilic/hydrophobic layers has shown promise for drug encapsulation and delivery. Saccharides have previously been incorporated to improve the biocompatibility of self-assembled structures; however, glycopolymer block copolymers have been less explored, and their structure-property relationships are not well understood. In this study, novel glycopolymer-branched poly(lactic acid) (PLA) block copolymers were synthesized via thiol-ene coupling and their composition-dependent morphologies were elucidated. Stability as a function of pH, dye uptake capabilities, and cytotoxicity were evaluated. Systems with a hydrophilic weight ratio of 30% were found to produce bilayer nanoparticles, while systems with a hydrophilic weight ratio of 60% form micelles upon self-assembly in aqueous media. Regardless of composition and morphology, all systems exhibited uptake of both hydrophobic (curcumin, DL % from 4.25 to 11.55) and hydrophilic (methyl orange, DL % from 4.08 to 5.88) dye molecules with release profiles dependent on composition. Furthermore, all of the nanoparticles exhibited low cytotoxicity, confirming their potential for biomedical applications.

In vitro and in vivo evaluation of a novel folate-based amphiphilic multifunctional stabilizer for targeting tumors with paclitaxel nanosuspensions

In order to improve the targeted delivery of the drug, a novel folic acid-modified paclitaxel nanosuspensions (FA-PEG-PTX NCs) delivery system was designed in the present study, and its target delivery ability was verified in vitro and in vivo models. Paclitaxel nanosuspensions were prepared by antisolvent precipitation using folic acid-modified polyethylene glycol monostearate (FA-PEG-MA) and D - α-tocopherol polyethylene glycol succinate (TPGS) as functional stabilizers. The FA-PEG-PTX NCs had an average particle size of 195.33 ± 13.31 nm, a PDI of 0.182 ± 0.022 and a zeta potential of - 12.4 ± 0.62 mV. The drug loading (DL) and encapsulation efficiency (EE) of FA-PEG-PTX NCs were 48.45 ± 3.34 % and 96.90 ± 1.81 %. Particle morphology showed that FA-PEG-PTX NCs had a rod-shaped structure with a smooth surface. XRD and DSC indicated that PTX existed mainly in an amorphous structure in the nanocrystals. FTIR showed no chemical reaction between PTX and stabilizer but rather physical interactions. In vitro dissolution experiments showed that nanocrystals significantly improved the PTX dissolution rate. Cytotoxicity assay and apoptosis assay showed that FA-PEG-PTX NCs had a stronger inhibitory effect on the proliferation and apoptosis of folate receptor-positive cells, Bel-7402 cells, compared with PEG-PTX NCs. In vivo studies showed that FA-PEG-PTX NCs and PEG-PTX NCs had long-lasting and targeted effects. In conclusion, FA-PEG-MA seems to be a promising stabilizer with targeting properties.

Tuning stiffness of hyaluronan-cholesterol nanogels by mussel-inspired dopamine-Fe3+ coordination: Preparation and properties evaluation

In the evolving field of nanomedicine, tailoring the mechanical properties of nanogels to fine-tune their biological performance is a compelling avenue of research. This work investigates an innovative method for modulating the stiffness of hyaluronan-cholesterol (HACH) nanogels, an area that remains challenging. By grafting dopamine (DOPA) onto the HA backbone, characterized through UV, 1H NMR, and FT-IR analyses, we synthesized a novel polymer that spontaneously forms nanogels in aqueous environments. These HACH-DOPA nanogels are characterized by their small size (~170 nm), negative charge (around −32 mV), high stability, efficient drug encapsulation, and potent antioxidant activities (measured by ABTS test). Leveraging mussel-inspired metal coordination chemistry, the DOPA moieties enable stiffness modulation of the nanogels through catechol-Fe3+ interactions. This modification leads to increased crosslinking and, consequently, nanogels with a significantly increased stiffness, as measured by atomic force microscopy (AFM), with the formation of the HACH-DOPA@Fe3+ complex being pH-dependent and reversible. The cytocompatibility was evaluated via WST-1 cell proliferation assays on HUVEC and HDF cell lines, showing no evident cytotoxicity. Furthermore, the modified nanogels demonstrated enhanced cellular uptake, suggesting their substantial potential for intracellular drug delivery applications, a hypothesis supported by confocal microscopy assays. This work not only provides valuable insight into modulating nanogel stiffness but also advances new nanosystems for promising biomedical applications.

Investigation of nanostructured lipid carriers for fast intracellular localization screening using the Echo liquid handler

In the field of precision medicine, therapy is optimized individually for each patient, enhancing efficacy while reducing side effects. This involves the identification of promising drug candidates through high-throughput screening on human derived cells in culture. However, screening of drugs which have poor solubility or permeability remains challenging, especially when targeting intracellular components. Therefore, encapsulation of drugs into advanced delivery systems such as nanostructured lipid carries (NLC) becomes necessary. Here we show that the cellular uptake of NLC with different matrix compositions can be assessed in a high-throughput screening system based on acoustic droplet ejection (ADE) technology (Echo liquid handler). Our findings indicate that surface tension and viscosity of the NLC dispersions need to be tailored to enable a reliable ADE transfer. The automated NLC uptake studies indicated that the composition of the matrix, more specifically the amount of oleic acid, significantly influenced cellular uptake. The data obtained were corroborated by imaging based and spectral flow cytometry cellular uptake studies. These findings thus not only provide the basis for a screening tool to rapidly identify the efficacy of NLC uptake but also enable a next step toward precision high-throughput drug screening under consideration of an optimized drug delivery system.

Tunable supramolecular self-assemblies based on cyclodextrin polymer as a loading platform for water-soluble drugs

Drug loading capacity is a crucial character of nano-scaled drug carriers to achieve high quality pharmaceutical preparations. However, efficient encapsulation of water-soluble small molecular drugs still faces large obstacles in many cases. Herein, we designed a novel supramolecular delivery system constructed by poly(β-cyclodextrin) containing benzoic acid groups (PCD-PA) and adamantyl terminated poly(ethylene glycol) (PEG-AD) to provide multiple intermolecular interactions for competent loading of water-soluble small-molecular drugs. PCD-PA had multiple host molecules, and PEG-AD could be inserted via host-guest interaction in different proportion to adjust the composition of supramolecular carrier. Meanwhile, π-π stacking and electrostatic interaction furnished by benzoic acid groups served as binding force for drug entrapment, which led to considerable loading capacity for several water-soluble drugs. Among the drugs with different chemical structures, mitoxantrone hydrochloride and doxorubicin hydrochloride bearing anthraquinone rings and several protonable amino groups acquired the highest loading content as about 14 % in PCD-PA3/PEG-AD supramolecular self-assemblies. Further computational simulations investigated the mechanism of drug loading based on the interactions between the carrier materials and the payloads. In addition, the weakly acidic environment obviously accelerated the release of certain drugs. All in all, this self-assembled supramolecular nano-system displayed great potentials as a delivery platform for diverse water-soluble drugs.

Doxorubicin-Intercalated Li-Al-Based LDHs as Potential Drug Delivery Nanovehicle with pH-Responsive Therapeutic Cargo for Tumor Treatment.

Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M+/M3+)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M+1-x M3+x (OH)]2x+[(Am-)2x/m. n(H2O)]2x-, which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li-Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Fabrication of PLA-Based Nanoneedle Patches Loaded with Transcutol-Modified Chitosan Nanoparticles for the Transdermal Delivery of Levofloxacin.

Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. Chitosan was chemically modified with transcutol in three ratios (1/1, 1/2, 1/3, w/w), and the optimum ratio was used for nanoparticle fabrication via the ionic gelation method. The successful modification was confirmed using ATR-FTIR spectroscopy, while DLS results revealed that only the 1/3 ratio afforded suitably sized particles of 220 nm. After drug encapsulation, the particle size increased to 435 nm, and the final formulations were examined via XRD and an in vitro dissolution test, which suggested that the nanoparticles reach 60% release in a monophasic pattern at 380 h. We then prepared transdermal patches with pyramidal geometry nanoneedles using different poly(lactic acid)/poly(ethylene adipate) (PLA/PEAd) polymer blends of varying ratios, which were characterized in terms of morphology and mechanical compressive strength. The 90/10 blend exhibited the best mechanical properties and was selected for further testing. Ex vivo permeation studies proved that the nanoneedle patches containing drug-loaded nanoparticles achieved the highest levofloxacin permeation (88.1%).

Lyotropic liquid crystal emulsions of LAVR-289: Influence of internal mesophase structure on cytotoxicity and in-vitro antiviral activity

Emerging and reemerging viruses pose significant public health threats, underscoring the urgent need for new antiviral drugs. Recently, a novel family of antiviral acyclic nucleoside phosphonates (ANP) composed of a 4-(2,4-diaminopyrimidin-6-yl)oxy-but-2-enyl phosphonic acid skeleton (O-DAPy nucleobase) has shown promise. Among these, LAVR-289 stands out for its potent inhibitory effects against various DNA viruses. Despite its efficacy, LAVR-289s poor water solubility hampers effective drug delivery. To address this, innovative delivery systems utilizing lipidic derivatives have been explored for various administration routes. Submicron lyotropic liquid crystals (LLCs) are particularly promising drug carriers for the encapsulation, protection, and delivery of lipophilic drugs like LAVR-289.This study focuses on developing submicron-sized lipid mesophase dispersions, including emulsified L2 phase, cubosomes, and hexosomes, by adjusting lipidic compounds such as Dimodan® U/J, Lecithins E80, and Miglyol® 812 N. These formulations aim to enhance the solubility and bioavailability of LAVR-289. In vitro evaluations demonstrated that LAVR-289-loaded LLCs at a concentration of 1 µM efficiently inhibited vaccinia virus in infected human cells, with no observed cytotoxicity. Notably, hexosomes exhibited the most favorable antiviral outcomes, suggesting that the internal mesophase structure plays a critical role in optimizing the therapeutic efficacy of this drug class.

Extracellular vesicles-hitchhiking boosts the deep penetration of drugs to amplify anti-tumor efficacy

Developing drug delivery systems capable of achieving deep tumor penetration is a challenging task, yet there is a significant demand for such systems in cancer treatment. Hitchhiking on tumor-derived extracellular vesicles (EVs) represents a promising strategy for enhancing drug penetration into tumors. However, the limited drug assembly on EVs restricts its further application. Here, we present a novel approach to efficiently attach antitumor drugs to EVs using an engineered cell membrane-based vector. This vector includes the AS1411 aptamer for tumor-specific targeting, the vesicular stomatitis virus glycoprotein (VSV-G) for tumor cell membrane fusion, and a photosensitizer as the therapeutic agent while ensuring optimal drug encapsulation and stability. Upon injection, photosensitizers are firstly transferred to the tumor cell membrane and subsequently piggybacked onto EVs with the inherent secretion process. By hitchhiking with EVs, photosensitizers can be transferred layer by layer deep into the solid tumors. The results suggest that this EVs-hitchhiking strategy enables photosensitizers to penetrate deeply into tumor tissue, thereby enhancing the efficacy of phototherapy. This study offers broad application prospects for delivering drugs deeply into tumor tissues.