Release Kinetics Research Articles

Methodology for high-performance liquid chromatography detection of latanoprost and latanoprost free acid

AbstractA gradient high-performance liquid chromatography (HPLC) method has been developed to determine the concentrations of latanoprost (LP) and latanoprost free acid (LPA) in aqueous solutions. It is novel due to a combination of its simplicity, speed, and detection capability in aqueous solutions for both active drug (LPA) and prodrug (LP). This method is applicable for the research and development of novel drug delivery devices and quality control assays for experimental and commercial laboratory settings, as it allows for a high sample throughput. Samples were chromatographed across a C18 + 2.7 µm 4.6 × 7.5 mm reversed-phase column with gradient elution using a mobile phase of aqueous acetic acid (pH 3.1) and acetonitrile with 0.1% acetic acid. UV spectrophotometry was used to monitor the eluents at 210 nm. Drug concentrations from 1.0 to 150 μg mL−1 were tested, with good linearity observed across the range. LPA had a signature peak at approximately 4.82 min (SD < 0.08) and LP at 9.27 min (SD < 0.07). For both drug and pro-drug, LOD and LOQ were 1.0 and 2.5 μg mL−1, respectively. This assay which accurately measures both prodrug and drug in a single injection, has significant applicability in determining the release kinetics of novel LP drug delivery systems.

Formulation and evaluation of hydrocortisone micro beads

The current study aimed to develop hydrocortisone mucoadhesive microbeads to prolong the drug's action in the gastrointestinal system, targeting Crohn's disease treatment. Hydrocortisone, known for its anti-inflammatory and anti-rheumatic effects, was utilized in bead form to enhance therapeutic efficacy, extend residence time, and reduce dosage frequency. Using sodium alginate, HPMC, and Eudragit L-100 as adhesive polymers, and calcium chloride and aluminium chloride as cross-linking agents, the study crafted microbeads with an entrapment efficiency between 57.23% and 91.69%. Evaluations focused on in vitro drug release, particle size, surface characteristics, entrapment efficiency, and the role of cross-linking ions. Of the formulations, HCS-8 (with sodium alginate and Eudragit L-100 using aluminium chloride as the gelling solution) and HCS-2 showed optimal drug release profiles. Notably, HCS-8 achieved a 12-hour drug release delay, attributed to aluminium chloride's cross-linking action. Drug release kinetics revealed a zero-order linearity (R2=0.99), suggesting super case 2 transport as the primary release mechanism.

Formulation and evaluation of pioglitazone microspheres

The current study focuses on the formulation, development, and in vitro testing of pologlitazone microspheres containing guar gum and chitosan as naturally occurring polysaccharides that delay release. Nine formulations were created by altering the chitosan and guar gum ratios, using span-85 as an emulsifier as well as glutaraldehyde as a chemical cross linking agent. The microspheres were assessed in terms of particle size, encapsulation effectiveness, drug loading capacity, and in vitro drug release tests. The average particle size ranged from 30.2 mm (PP 1) to 36.5 mm (PP 2). There was a range of 0.45 to 0.78 in the swelling index. Microspheres smooth surfaces were found by SEM investigation. In order to verify that there are no chemical interactions between the medication and the polymer and to understand the structure of microspheres, differential scanning calorimetry as well as Fourier transform infrared spectroscopy were employed. At 10 hours, the optimised batch PP 1 released 97.45% using phosphate buffer pH7.4 as a dissolving media. In terms of release kinetics, the optimised formula's data were best fitted with the Higuchi model (r2= 0.671) and demonstrated zero order release (r2= 0.980) via a non-Fickian diffusion mechanism.

Computational analysis of clindamycin-loaded PLGA and Gly-PLGA carriers in order to enhance drug delivery efficiency using DFT and MD simulation

In this study, the potential of clindamycin (CMC) interacting with poly(lactic-co-glycolic acid) (PLGA) and glycine-poly(lactic-co-glycolic acid) (Gly-PLGA) for drug delivery applications was explored using density functional theory (DFT) and molecular dynamic (MD) calculations. Various chemical properties, including electronic structure, infrared (IR) spectra, optical properties, and adsorption energy, were investigated to gain insights into the behavior of these systems. The electronic structures of CMC@PLGA and CMC@Gly-PLGA were examined, revealing significant modifications and suggesting improvements in drug release kinetics and stability. MD simulation reveals the hydrogen bonding interaction between CMC and PLGA molecules, typically within 2 to 3 Å, facilitating effective CMC delivery. The optical and infrared (IR) spectra were analyzed, identifying characteristic absorption and vibrational modes and providing understanding of structural changes and interactions within the drug-polymer system. The adsorption energy between CMC and PLGA was evaluated, showing a favorable binding affinity, which suggests potential for sustained drug release and improved therapeutic efficacy. The density of state (DOS) analysis showed that when CMC is adsorbed, it undergoes strong electron hybridization, leading to significant changes in the electronic properties of PLGA, making it highly sensitive to CMC binding.

Red mud modified phosphogypsum based self-leveling mortar: Hydration mechanism, heavy metal migration law and spatial distribution characteristics

In the production processes of phosphoric acid and alumina, chemical enterprises generate solid waste such as red mud (RM), phosphogypsum (PG), and fly ash (FA). The environmentally friendly utilization of these waste materials is of crucial significance. Therefore, this study focuses on investigating the impact of collaborative modification using diverse solid wastes on the macroscopic properties and internal microstructure of self-leveling mortar. Through a careful selection process, the optimal ratio for red mud and phosphogypsum self-leveling mortar(RPSM) has been identified during the research. This study not only provides substantial support for the effective utilization of solid waste but also contributes to the improvement of overall performance and structural characteristics of the mortar. Based on this, the hydration characteristics, leaching patterns, and spatial distribution characteristics of heavy metals in RPSM were evaluated. The research revealed that the optimal ratios of RM, PG, FA, PC, river sand, and heavy calcium carbonate powder in RPSM were 20.7%, 13.8%, 17.1%, 13.8%, 17.3%, and 17.3%, respectively. Under a water-binder ratio of 0.18, the flexural and compressive strength of the mortar specimens after 14 d of curing can reach 4.3 and 31.6 MPa. Through comprehensive analysis and discussion of the performance, microstructure, and dynamics of the hydration process of RPSM, the main processes of mortar hydration were elucidated. Environmental risk assessments indicated no environmental risks from heavy metals in RPSM. Human health risk assessment suggested carcinogenic risks from Cr and Cd in RPSM through oral exposure, leading to restrictions on the content of characteristic heavy metals in different application scenarios. Furthermore, fitting results of the release kinetics of heavy metals indicated that the leaching of heavy metals in RPSM can be well fitted with kinetic models, allowing the determination of the optimal safe age of RPSM containing harmful heavy metals. Finally, using interpolation and vertical distribution simulation by software such as ArcGIS, the spatial distribution characteristics of heavy metals in RPSM during use were analyzed. The research can supply fundamental academic support for the recycling of solid wastes like RM and the control of environmental risks associated with heavy metal leaching in building materials.

The Emerging Trends of 3d Printing Techniques in Pharma Sector

Technology involving 3-dimensional printing has begun to revolutionize several fields, including pharmacy. In pharmacy, it offers a reliable avenue for precision medicine, dosage forms and drug delivery systems. The creation of complex drug structures with precise control over composition, shape and release kinetics, catering to individual patient needs has been possible with the intervention of this method. One significant utilization in pharmacy is the customization of dosage forms. Traditional manufacturing methods often struggle to produce tailored medications for patients with unique requirements, such as paediatric or geriatric populations. With 3D printing, pharmacists can create personalized medication with appropriate dosages, structures, and release kinetics, improving patient adherence and beneficial results. Moreover, sophisticated medication delivery systems may be created thanks to 3D printing. For instance, multi- layered tablets can be designed to release multiple drugs at different rates, optimizing treatment regimens for conditions requiring combination therapies. Furthermore, intricate structures like porous scaffolds or micro needle arrays can facilitate targeted drug delivery, enhancing bioavailability and minimizing side effects. Additionally, 3D printing facilitates the rapid prototyping of pharmaceutical formulations, accelerating the drug development process. Researchers can efficiently iterate through various designs, optimizing formulations for efficacy, stability and manufacturability. Despite its promise, challenges remain in integrating 3D printing into mainstream pharmacy practice, including regulatory hurdles, material selection and scalability issues. However, ongoing advancements in technology and collaborations between academia, industry and regulatory agencies are driving progress in overcoming these barriers. In conclusion, 3D printing technology holds immense potential to transform pharmacy by enabling personalized medicine, new dosage formulations and cutting-edge medication delivery technologies. As research and development in this field continue, the prospect of tailored pharmaceuticals tailored to individual patient needs becomes increasingly attainable.

Direct visualization of pyrene diffusion in polyethylene and polyoxymethylene passive samplers

While passive sampling of ultra-low aqueous concentrations of hydrophobic organic compounds in environmental aqueous media has emerged as a promising analytical technique, there is a lack of good understanding of the fundamental diffusive processes. In this research, we used a fluorophore, pyrene, as a model compound to track diffusion in polymers through absorption and environmental media exchange processes. We directly tracked the penetration of pyrene into polyethylene (PE) and polyoxymethylene (POM) rods during absorption from water by sectioning the rod after different stages of absorption and observing the fluorescence signal through a microscope. Diffusion profiles of pyrene in polymers were simulated by numerical integration of Fickian diffusion. The results indicated that the uptake process in PE is governed by Fick's law and the absorption and desorption kinetics are similar in this polymer. However, the observed uptake profiles of pyrene in POM were non-Fickian and the release kinetics out of POM was slower compared to uptake into the polymer. We show that slower desorption from POM makes corrections for nonequilibrium using performance reference compounds (PRCs) problematic for deployments in water or sediment where there is significant advection. However, for static sediment deployments, the overall kinetics of exchange is controlled by slow transport through sediment and the hysteretic behavior of POM may not preclude the use of PRCs to interpret equilibrium status.

Formulation and optimization of electrospun nanofiber films for ultrafast delivery of domperidone: In vitro and in-vivo characterization

Nanotechnology has significantly transformed drug delivery approaches by providing precise control of drug release kinetics and enhancing therapeutic effectiveness. Electrospun nanofiber films have unique features, including a significant surface-to-volume ratio and substantial porosity, resulting in enhanced patient adherence. The study was aimed at developing electrospun nanofiber films of domperidone for ultrafast release using polyvinyl alcohol (PVA). The nanofibers were prepared by electrospinning method and optimized using 32 factorial design. Electrospinning process parameters like feed rate, applied electric voltage, and tip-to-collector distance were optimized. The prepared nanofiber film was characterized using scanning electron microscopy, differential scanning calorimetry (DSC), Fourier transform infrared microscopy (FTIR), X ray diffraction (XRD), in-vitro diffusion, and permeation studies. The resultant domperidone-loaded nanofibers (diameters 280–565 nm) exhibited a uniform and highly porous structure. With an increase in applied voltage from 11 to 13 kV, entrapment efficiency increased, and fiber diameter decreased. DSC and XRD results confirmed the amorphous nature of the domperidone. The FTIR study confirmed the compatibility between domperidone and PVA. The wetting and disintegration times of nanofibers were 8 and 4 s, respectively. Due to their nanosize, small particles with an increased surface area resulted in improved drug delivery through nanofibers (93.36% release within 10 min). The nanofiber film had a higher Cmax (398.8 ng/mL) and AUC (2078.593 ± 17.71 ng/mL.h) than the commercial tablet formulation (186.6 ng/mL and 1875.619 ± 10.38). Thus, domperidone nanofibers would be a promising approach for enhancing therapeutic and biopharmaceutical properties by providing ultra-fast delivery.

Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy

AbstractThe treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to the deficiency in mechanical support and controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for exosomes wrapping. This injectable KeMA hydrogel, initiated by a biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone and N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, and excellent cytocompatibility. In vitro studies showcased that the exosomes‐loaded KeMA hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered extracellular matrix (ECM) regeneration, and reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling for matrix regeneration and NF‐κB signaling inhibition for anti‐inflammation. In vivo IVDD rat models demonstrated Exo@KeMA attenuated inflammation, maintained NP water content, preserved disc height, and promoted structural regeneration. This research introduces an injectable KeMA hydrogel as a promising therapy for IVDD, by facilitating biomechanics restoration, anti‐inflammatory response, and ECM regeneration.

Sustained release local anesthetics for pain management: relevance and formulation approaches.

This review attempted to ascertain the rationale for the formulation of sustained-release local anesthetics and summarize the various formulation approaches designed to date to achieve sustained and localized local analgesic effects. The incidence of pain, which is the concern of patients as well as health care professionals, is increasing due to accidents, surgical procedures, and other diseases. Local anesthetics can be used for the management of moderate to severe acute and chronic pain. They also allow regional analgesia, in situations where the cause and source of the pain are limited to a particular site or region, without the need for loss of consciousness or systemic administration of other analgesics thereby decreasing the risk of potential toxicities. Though they have an interesting antipain efficacy, the short duration of action of local anesthetics makes the need for their multiple injections or opioid adjuvants mandatory. To overcome this problem, different formulations are being designed that help achieve prolonged analgesia with a single dose of administration. Combination with adjuvants, liposomal formulations, lipid-based nanoparticles, thermo-responsive nanogels, microspheres, microcapsules, complexation with multivalent counterions and HP-β-CD, lipid-based nanoparticles, and bio-adhesive films, and polymeric matrices are among the approaches. Further safety studies are required to ensure the safe and effective utilization of sustained-release local anesthetics. Moreover, the release kinetics of the various formulations should be adequately established.

Bioactive molecule-based nano-particulate drug delivery system for antifertility activity

Current research work was design to develop bioactive molecule (Plumbagin) loaded nanoparticle formulation by using Design of experiment to investigate its formulation characteristics and in-vivo antifertility activity. Plumbagin belongs to the (Plumbaginaceae) family and mostly obtained from plant Plumbago indica Linn. Insolubility, instability and poor bioavailability are the factors which constrained in designing formulation of plumbagin. In order to overcome these factors, nanoparticles loaded plumbagin were formulated, this modified delivery system not only enhances the solubility and stability of plumbagin by reducing the particle size from thousands to a few hundred nanometers; when the size decreases, the active ingredient’s bioavailability increases. However, it also aids in enhancing the antifertility activity’s impact. Optimized formula was selected on the basis of design expert software and characterized. As a result, the optimized formula showed Particle size was 397.4 nm, shape of the nanoparticle was spherical detected by Scanning Electron Microscopy, Entrapment efficiency was 67.49 ± 0.047% and Zeta Potential was 25.0 mV. The disruption of the estrous cycle is indicated by the drop in FSH levels found in the in-vivo investigation. An in-vivo study reveals that the reproductive rate of albino wistar rats is decreasing. It was also discernible on the histology slide of the uterus and ovaries of the female albino rat. Follicle counts can yield valuable insights into the ovary’s functioning, particularly on the interplay between the mechanisms that control and facilitate folliculogenesis. At all test levels, no adverse symptoms were seen in any of the experimental groups after treatment. Due to high entrapment efficiency, stability, kinetics of release under simulated physiological conditions, and increased antifertility activity indicated that eudragit based nanoparticle formulation provide appropriate delivery system for Plumbagin.

Comparative analysis of hydrogen uptake and release kinetics in MgH2/C composites synthesized using varied surface areas graphite powders

Comparative analysis of hydrogen uptake and release kinetics in MgH2/C composites synthesized using varied surface areas graphite powders

The contemplation of amylosefor the delivery of ulcerogenic nonsteroidal anti-inflammatory drugs.

This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked withnonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility andbiodegradability, as well asits capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.

Novel Phytosomal Formulation of Emblica officinalis Extracts with Its In Vivo Nootropic Potential in Rats: Optimization and Development by Box-Behnken Design

Purpose. The present study aimed to improve the aqueous solubility, permeability, bioavailability, and nootropic potential of standardized Emblica officinalis extract (EOE) by developing a novel phytosomal formulation. Method. Emblica officinalis extract-loaded phytosomes (EOPs) were prepared using solvent evaporation. The EOP was prepared at different molar ratios of extract and phospholipid. Herein, the effects of phospholipid extract ratio (A), temperature (B), and reaction time (C) were systematically investigated on entrapment efficiency using Box-Behnken design. In vitro and in vivo characterizations of the optimized formulation were performed. Results. Optimized EOP formulation (89.90 ± 0.24 μg/ml) exhibited improved aqueous solubility than plain EOE (11.85 ± 0.25 μg/ml). The optimized formulation’s particle size and Zeta potential were 198.4 ± 0.20 nm and −39.0 ± 0.40 mv. DSC and XRD studies confirmed the partial amorphization of EOE in phytosomes. Optimized formulation exhibited 69.82 ± 0.17% of EOE release at 12 h and followed zero-order release kinetics. Moreover, the phytosomal formulation of EOE exhibited its rationality with an improvement of bioavailability by 2.7 folds compared with pure EOE. Compared to EOE, EOP showed significantly (p<0.05 lower escape and transfer latencies on both days in MWMT and EPMT, indicating more effective memory-enhancing activity. Furthermore, EOP-treated rats exhibited improved acetylcholine (Ach) levels than EOE. Brain tissue concentrations measured following EOP oral administration (1.06 ± 0.04 μg/ml) were substantially greater (p<0.05) than those following EOE (0.32 ± 0.07 μg/ml). The brain dopamine and serotonin concentration were found to be higher (16.27 ± 1.209 and 43.28 ± 1.550 ng/ml) in the EOP-treated group as compared to the pure extract-treated group (10.40 ± 1.185 and 32.79 ± 1.738 ng/ml). Conclusion. Improvement of aqueous solubility, permeability, dissolution, bioavailability, and narrower particle size distribution could facilitate enhancement in the nootropic potential of EOE phytosomal formulation.

Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector.

Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

Encapsulation of beetroot extract (Beta vulgaris L.) obtained by internal and external ionic gelation: a comparative study

Natural pigments, like betalains found in beets, are sensitive to environmental conditions, which may impact their reactivity and shelf-life. Microencapsulation is an attractive alternative for delivering these compounds, offering protection through polymeric microcapsules. The aim of this study was to compare two ionic gelation methodologies, external (EG) and internal gelation (IG), in the microencapsulation of beet aqueous extract. Particles were obtained by mixing sodium alginate with the aqueous extract of beetroot and crosslinking with calcium chloride solution using the extrusion method. Encapsulation characteristics and physical, morphological features were evaluated. The particles showed 10.72 and 89.90% encapsulation efficiency for EG and IG, respectively. Loading capacity was 18.90% for EG and 25.60% for IG. Those IG particles showed superior water absorption capacity during rehydration. Texture analysis indicated that EG particles showed greater hardness. Release kinetics indicated that EG particles followed the Korsmeyer-Peppas model, while IG particles followed the Higuchi model. Thus, the appropriate encapsulation technique should be selected depending on the food matrix to be used and the specific objective of delivering the active encapsulated molecules.

Kinetics of Intermediate Release Enhances P450 11B2-Catalyzed Aldosterone Synthesis.

The mitochondrial enzyme cytochrome P450 11B2 (aldosterone synthase) catalyzes the 3 terminal transformations in the biosynthesis of aldosterone from 11-deoxycorticosterone (DOC): 11β-hydroxylation to corticosterone, 18-hydroxylation, and 18-oxidation. Prior studies have shown that P450 11B2 produces more aldosterone from DOC than from the intermediate corticosterone and that the reaction sequence is processive, with intermediates remaining bound to the active site between oxygenation reactions. In contrast, P450 11B1 (11β-hydroxylase), which catalyzes the terminal step in cortisol biosynthesis, shares a 93% amino acid sequence identity with P450 11B2, converts DOC to corticosterone, but cannot synthesize aldosterone from DOC. The biochemical and biophysical properties of P450 11B2, which enable its unique 18-oxygenation activity and processivity, yet are not also represented in P450 11B1, remain unknown. To understand the mechanism of aldosterone biosynthesis, we introduced point mutations at residue 320, which partially exchange the activities of P450 11B1 and P450 11B2 (V320A and A320V, respectively). We then investigated NADPH coupling efficiencies, binding kinetics and affinities, and product formation of purified P450 11B1 and P450 11B2, wild-type, and residue 320 mutations in phospholipid vesicles and nanodiscs. Coupling efficiencies for the 18-hydroxylase reaction with corticosterone as the substrate failed to correlate with aldosterone synthesis, ruling out uncoupling as a relevant mechanism. Conversely, corticosterone dissociation rates correlated inversely with aldosterone production. We conclude that intermediate dissociation kinetics, not coupling efficiency, enable P450 11B2 to synthesize aldosterone via a processive mechanism. Our kinetic data also suggest that the binding of DOC to P450 11B enzymes occurs in at least two distinct steps, favoring an induced-fit mechanism.

Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions

Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses.

Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N2 adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses.