Potential Controlled Release Research Articles

Preparation and characterization of micellar nanoparticles using crude saponins from five Congolese plant species

Nanoparticles (NPs) have significantly advanced medical applications, including drug delivery, immunotherapy, vaccines, and diagnostics. This versatility is partly due to the potential of tailoring NPs from multiple sources. Notably, saponins, amphiphilic plant metabolites, have shown great promise in NP formulation. This study explored the development of micellar NPs using saponin crude fractions (SCFs) extracted from five Congolese plant species: Millettia laurentii, Penthaclethra eetveldeana, Schwenckia americana, Musa paradisiaca, and Musa sapientum. Plant materials were subjected to histological examination through optical microscopy, while phytochemical analyses by thin-layer chromatography confirmed the presence and predominance of saponins in the SCFs. We used a phthalocyanine-isoniazid hybrid (Pc-INH) as a hydrophobic probe to determine the critical micellar concentrations of SCFs and explore the feasibility of developing cost-effective saponin-based micelles (SBMs). Phytochemical screenings indicated saponins in the extracted SCF and other metabolites like flavonoids, phenolic acids, and anthocyanins. Dynamic light scattering and transmission electron microscopy analyses revealed the formation of nano-sized particles, particularly noting SBMs from P. eetveldeana with notable dimensions (157 ​nm, PDI of 0.27, and ZP of −4.01 ​mV) and spherical shape. The micelles from M. laurentii exhibited superior encapsulation efficiency for Pc-INH (55%) compared to control micelles formulated from pure saponin (33%). In vitro tests showed that M. paradisiaca SBMs have the best safety profile for red blood cells, with a 10% hemolysis rate compared to a 150% rate for bulk SCFs. However, there is a significant difference between SCFs and SBMs (p ​< ​0.0001). The release profiles of M. paradisiaca SBMs show a pH-dependent relationship, suggesting potential for stimuli-responsive drug delivery. This work lays the foundation for leveraging plant-derived crude saponins in nanotechnology, emphazising their encapsulation efficiency, controlled release potential, and biocompatibility, paving the way for the cost-effective production of high-value biomedical NPs.

Machine Learning and Hyperspectral Imaging for Analysis of Human Papillomaviruses (HPV) Vaccine Self-Healing Particles.

Human papillomaviruses (HPV) are known to cause a variety of diseases, including cervical cancer and genital warts. HPV is a highly prevalent virus and is considered the most common sexually transmitted disease. Because of the risks associated with HPV, Gardasil, a quadrivalent recombinant vaccine, was developed by Merck & Co., Inc., Rahway, NJ, USA, and approved by the Food and Drug Administration (FDA) in 2006. The second generation of the vaccine, Gardasil9, was subsequently approved by the FDA in 2014, providing significant protection against HPV. The HPV vaccine may be given as 2 or 3 doses; however, vaccine administration as a single dose with a sustained release mechanism may potentially offer benefits to meet emerging health needs. To explore this, HPV vaccines were formulated within microporous self-healing particles (SHPs) to enable potential controlled release of HPV virus-like particle (VLP) antigen. Machine learning, in the form of multivariate curve resolution-alternating least-squares (MCR-ALS), with Raman hyperspectral imaging was used to determine the molecular identity and spatial distribution of all relevant species within this HPV vaccine formulation. The results indicate that machine learning with Raman hyperspectral imaging was able to spatially resolve HPV VLP antigens within SHP vaccines for the first time, providing crucial information necessary for vaccine development.

Preparation of melamine-functionalized mesoporous silica nanoparticles for delivery of anticancer drugs

The surface-grafted mesoporous silica nanoparticles attract interest in drug delivery, owing to their high drug loading and controlled release potential to the target sites. In this paper, we propose the synthesis of mesoporous silica nanoparticles and their surface grafting using melamine groups for pH-responsive release of anticancer drugs. A model anticancer drug, 5-fluorouracil (5-Fu) was used to encapsulate into the melamine-grafted mesoporous silica nanoparticles (M−MS/5-Fu NPs) using the solvent immersion method. pH and temperature-responsive release behavior of the M−MS/5-Fu NPs were verified at different pH (pH 7.4, 6.5, and 4.0). Further, the in vitro cytotoxicity of the prepared samples was also evaluated on the MCF-7 cell line.

The Effect of Polymer-Solvent Interaction on the Swelling of Polymer Matrix Tablets: A Magnetic Resonance Microscopy Study Complemented by Bond Fluctuation Model Simulations.

Polymer matrix tablets are an important drug-delivery system widely used for oral drug administration. Understanding the tablet hydration process, both experimentally and theoretically, is, thus, very important for the development of drug delivery systems that exhibit high drug loading capacity and controlled release potential. In this study, we used magnetic resonance microscopy (MRM) to nondestructively and dynamically analyze the water hydration process of xanthan-based tablets. The swelling process was characterized by well-resolved fronts of erosion, swelling, and penetration. The experimental results were complemented by numerical simulations of the polymer matrix hydration process. In the simulations, the polymer tablet matrix was modeled as an assembly of interacting chains with embedded drug particles, while its hydration process was mediated by interaction with solvent particles. The swelling dynamics were modeled within a Monte Carlo-based bond fluctuation model (BFM) that elegantly accounted for steric and nearest-neighbor interactions. This study provides an efficient experimental-theoretical approach for the study of polymer matrix swelling processes.

Development of Modified-Release Diclofenac Sodium Capsules Using Blends of Pectin-Clay Multiparticulate Hybrid Systems as Release Retardants

A combination of inorganic and organic hybrid systems is of high research interest as they provide novel hybrid systems for the improvement of existing properties, overcoming limitations of the parent materials, and for the optimization of their controlled release potential. This study sorted to develop and pharmaceutically assess the release profile of diclofenac sodium using cocoa pod husk (CPH) blended with different proportions of either talc or bentonite as multiparticulate composite release modifiers. Preformulation investigations of the multiparticulate hybrid systems included pH, swelling index, moisture content, elemental contents, and flow properties. The FTIR was also used to investigate the compatibilities between pectin and bentonite (PB), pectin and talc (PT), and diclofenac and pectin-talc (DPT), as well as diclofenac and pectin-bentonite (DPB). The diclofenac content, uniformity of the weight of capsules, in vitro drug release, and the kinetics and mechanism of release of diclofenac from the hybrid systems were also investigated using mathematical models. The pectin yield was 23.3%, with the water-holding capacities of pectin-talc (PT) and pectin-bentonite (PB) hybrid systems being 6.4% and 5.0%, respectively. The swelling indices of PT and PB were 110.0 and 130.0 in 0.1 M HCL at pH 1.2 and 130.0 and 149.0 in phosphate buffer at pH 6.8, respectively. This system was also found to exhibit excellent flow properties, and there were no diclofenac-excipient interactions. All formulated batches passed the pharmacopoeial and nonpharmacopoeial tests. They also demonstrated controlled release properties via different release kinetics and mechanisms. This study shows that the pectin-talc and pectin-bentonite multiparticulate composites could be used as release modifiers in pharmaceutical preparations.

Toward function starch nanogels by self-assembly of polysaccharide and protein: From synthesis to potential for polyphenol delivery

Nanogels formed by self-assembly of natural proteins and polysaccharides have attracted great interest as potential carriers of bioactive molecules. Herein, we reported that carboxymethyl starch-lysozyme nanogels (CMS-Ly NGs) were prepared using carboxymethyl starch and lysozyme by green and facile electrostatic self-assembly, and the nanogels served as epigallocatechin gallate (EGCG) delivery systems. The dimensions and structure of the prepared starch-based nanogels (i.e., CMS-Ly NGs) were characterized by dynamic light scattering (DLS), ζ-potential, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermal gravimetric analyzer (TGA). FT-IR and 1H NMR spectra together confirmed the formation of CMS; FT-IR spectra confirmed the formation of CMS-Ly NGs; XRD spectra confirmed the disruption of the crystal structure of lysozyme after electrostatic self-assembly with CMS, and further confirmed the formation of nanogels. TGA demonstrated the thermal stability of nanogels. More importantly, the nanogels showed a high EGCG encapsulation rate of 80.0 ± 1.4 %. The CMS-Ly NGs encapsulated with EGCG exhibited regular spherical structure and stable particle size. Under the simulated gastrointestinal environmental conditions, CMS-Ly NGs encapsulated with EGCG showed the controlled release potential, which increased its utilization. Additionally, anthocyanins can also be encapsulated in CMS-Ly NGs and showed slow-release properties during gastrointestinal digestion in the same way. Cytotoxicity assay also demonstrated good biocompatibility between CMS-Ly NGs and CMS-Ly NGs encapsulated with EGCG. The findings of this research suggested the potential application of protein and polysaccharides-based nanogels in the delivery system of bioactive compounds.

Synthesis of pH/ temperature sensitive gelatin/peptide composite hydrogels and its characterization for potential controlled drug release applications

Conventional self-assembled peptide hydrogels have poor mechanical properties and tend to release abruptly when they are used as drug carriers, limiting the application of these materials in biomedical field. In this work, gelatin was embedded in a pH-responsive peptide Ac-FALNLAKD-NH2 (PEP) to construct gelatin/peptide composite hydrogels (Gel/PEP) for controlling the delivery of the anticancer drug chelerythrine (CHE). The physicochemical properties of Gel/PEP composite hydrogels were evaluated. The results of circular dichroism and Fourier transform infrared spectroscopy characterization showed that compared with PEP hydrogels and gelatin, the Gel/PEP composite hydrogel has a superposition of two secondary structures, in which β-sheet and random coil accounted for 44.7 % and 55.3 % of the conformation, respectively. Rheology and scanning electron microscope characterization confirmed that the Gel/PEP hydrogel has a highly dense nanofibrous meshwork structure, which enhances mechanical and injectable properties. In addition, the encapsulation rate of CHE could reach more than 97 % at a gelatin/peptide mass ratio of 7:1. More importantly, in vitro results showed that the composite hydrogel still had good pH and thermal response performance, which can achieve controlled release of CHE. Therefore, it is possible to synthesize supramolecular drug release soft materials by composite of gelatin and peptide hydrogels.

Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.

The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophages in vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammation in vivo over 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effects in vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG. STATEMENT OF SIGNIFICANCE: SG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.

Influence of Polymeric Microparticle Size and Loading Concentration on 3D Printing Accuracy and Degradation Behavior of Composite Scaffolds.

Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, machine precision, and degradation of 3D printed poly(ɛ-caprolactone)-based scaffolds. Using a main effects analysis, the sizes and loading concentrations of particle delivery vehicles investigated were found to have neither a beneficial nor disadvantageous influence on the metrics of printing quality such as material accuracy and machine precision. Meanwhile, particle loading concentration was determined to influence degradation rate, whereas printing temperature affected the trends in composite weight-average molecular weight. Neither of the two particle-related parameters (concentration nor diameter) was found to exhibit a significant effect on intra-fiber nor inter-fiber porosity. These findings evidence the capacity for controlled loading of particulate delivery vehicles in 3D printed scaffolds while preserving construct accuracy and precision, and with predictable dictation of composite degradation behavior for potential controlled release of encapsulated biomolecules.

Efficacy and safety of nanoparticles of glibenclamide and organomodified layered double hydroxides in diabetics rats

Glibenclamide (GB) is an important drug in the treatment of type II diabetes mellitus (DM II); however, its low solubility causes variability in its oral bioavailability, negatively affecting the pharmacological treatment. Nanoparticles (NP) of GB and organophilized Layered Double Hydroxide (LDH) were developed to improve oral bioavailability and tested in streptozotocin-induced diabetic rats to evaluate therapeutic efficacy and safety. Blood glucose was measured for 12 h or after 28 days of treatment. In addition, body weight, water and feed consumption, hematological, biochemistry and morphological parameters and markers of oxidative stress were determined. After the treatment, GB with LDH normalized the blood glucose level, indicating a better release profile. Water and feed intake and body weight of animals treated with GB and GB with LDH were closer to the normoglycemic group and did not indicate signs of toxicity of the nanoparticles. The biochemical, hematological and histological results also showed no significant changes related to nanotoxicity. The combination of GB with LDH proved to be critical in the oxidative balance, as it reduced the oxidative stress of vascular tissue. In conclusion, NPs are a potential controlled release system for the treatment of DM II.

Structurally stable polyvinyl alcohol/sodium alginate-based optimally designed electrospun mats as mechanistically robust controlled-urea-release-systems

The present study deals with the development of uniform, bead-free, and urea-loaded PVA/SA-based sustainable electrospun fibrous constructs as a controlled release fertilizer system. Taguchi L9 OA was used to predict the optimal level of control parameters i.e., urea loading (∼ 45 phr), flow rate (∼ 1 ml/h), polymeric concentration (∼ 8 wt%), and an applied voltage of ∼ 25 kV, to fabricate EMs with minimum fiber diameter (∼ 0.208 µm) and diametral variation (∼ 0.017 µm). Microstructural analysis confirmed the presence of hydrogen bonding interactions between urea and the polymer matrix, as well as successful ionic crosslinking. The contact angle and thermogravimetric analysis indicated an increase in hydrophobicity (from ∼ 30.64º to ∼ 74.13º) and thermal stability (from 164 ºC to ∼ 290 ºC) for PVA/SA-based EMs upon urea incorporation and post crosslinking, respectively. Further, the effect of urea loading and crosslinking on swelling and degradation behavior revealed a subsequent increase in water absorption capacity up to ∼ 296 % accompanied by a decrease in degradation rate up to ∼ 13%. The swelling behavior of EMs exhibited a desirably good level of pH level, salt/alkali solution sensitivity, and water retention potential lasting up to ∼16 days in soil. Spectroscopic analysis revealed a non-Fickian diffusion-induced sustained release of urea in water (> 21 days) and soil media (> 30 days). Soil burial studies of crosslinked urea-loaded EMs exhibited excellent biodegradability (> 80 % in 60 days) and structural stability (∼30 days). Thus, the study demonstrated the design of mechano-functionally engineered urea-loaded optimized PVA/SA-based EMs as potential controlled nutrient release substrates with improved and sustainable physicomechanical performance for agricultural practices.

Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel.

Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its in vivo persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the in vitro and in vivo release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K2(SL)6K2 (abbreviated as K2), that has been previously used for the controlled release of protein and small molecule payloads. We observed that O-Man released more slowly from K2 hydrogels in vitro than R-Man. In vivo, the clearance of O-Man from K2 hydrogels was slower than O-Man alone. We attributed the slower release rate to the formation of dynamic imine bonds between reactive aldehyde groups on O-Man and the lysine residues on K2. This imine interaction was also observed to improve K2 + O-Man hydrogel strength and shear recovery without significantly influencing secondary structure or peptide nanofiber formation. There were no observed differences in the in vivo release rates of O-Man loaded in K2, R-Man loaded in K2, and R-Man alone. These data suggest that, after subcutaneous injection, R-Man naturally persists longer in vivo than O-Man and minimally interacts with the peptide hydrogel. These results highlight a potentially critical, but previously unreported, difference in the in vivo behavior of O-Man and R-Man and demonstrate that K2 can be used to normalize the release of O-Man to that of R-Man. Further, since K2 itself is an adjuvant, a combination of O-Man and K2 could be used to enhance the immunostimulatory effects of O-Man for applications such as infectious disease vaccines and cancer immunotherapy.

Effect of drug load and lipid–wax blends on drug release and stability from spray-congealed microparticles

This study was designed to evaluate paraffin wax as a potential controlled release matrix for spray congealing and its impact on drug release and stability of the microparticles. Paraffin wax can form a hydrophobic barrier to moisture and reduce drug degradation besides retarding drug release in the gastrointestinal tract. More hydrophilic lipid-based additives can be incorporated to modulate the drug release through the paraffin wax barrier. This study reports the findings of lipid–wax formulations at preserving the stability of moisture-sensitive drugs in spray-congealed microparticles. Aspirin-loaded microparticles formulated with different drug loads, lipid additives, and lipid:wax ratios were produced by spray congealing. Stearic acid (SA), cetyl alcohol (CA), and cetyl ester (CE) were the lipid additives studied. The microparticles were evaluated for yield, encapsulation efficiency, particle size, drug stability, and release. CE exhibited the greatest effect on increasing drug release, followed by CA and SA. Dissolution profiles showed the best fit to Weibull kinetic model. The degree of drug degradation was low, with CA imparting the least protective effect, followed by SA and CE. Paraffin wax is useful for preserving the stability of moisture-sensitive aspirin and retarding its release from spray-congealed microparticles. The addition of lipid additives modulated drug release without compromising drug stability.

Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery

Nanostructured lipid carriers (NLC) are novel lipidic nanosystems that provide significant improvements in terms of high drug loading capacity and controlled drug release. The purpose of the present work was based on the design, development, and physicochemical characterization of lactoferrin-loaded NLCs as a new therapeutic alternative for the keratoconus treatment. Lactoferrin-loaded NLCs were successfully prepared by a double emulsion/solvent evaporation method. The resultant NLC were assessed in terms of particle size, size distribution, surface charge, morphology, encapsulation efficiency (EE), loading capacity (LC), stability, cytotoxicity, in vitro release, and ocular surface retention. Resulting data showed a size of 119.45 ± 11.44 nm, a 0.151 ± 0.045 PDI value and a surface charge of −17.50 ± 2.53 mV. Besides, high EE and LC values were obtained (up to 75%). The in vitro release study demonstrated a lactoferrin controlled release pattern. NLCs were also stable, non-toxic and show mucoadhesive properties. Thus, a consistent preclinical base was obtained, where NLC may be considered as a potential controlled release novel drug delivery system of lactoferrin for the keratoconus treatment.

Pluronic F127-co-poly (2 acrylamido-2-methylpropane sulphonic acid) crosslinked matrices as potential controlled release carrier for an anti-depressant drug: in vitro and in vivo attributes

Pluronic F127-co-poly (2 acrylamido-2-methylpropane sulphonic acid) crosslinked matrices as potential controlled release carrier for an anti-depressant drug: in vitro and in vivo attributes

Magnesium Aluminium Silicate-Metformin Hydrochloride Complexes - The Use of Isothermal Calorimetry for Probing Clay and Drug Nanocomplexations.

Studying complexation between a wide variety of drugs and clay is of high importance in expanding the knowledge about controlled drug delivery and its exploitation. This study reports the use of isothermal calorimetry (ITC) in understanding the complexation process occurring between magnesium aluminium silicate (MAS) and metformin hydrochloride (MET), as a potentially controlled release drug delivery system. To fully characterise and understand the complexes formed between MAS and MET and how that might impact on controlled release systems. MAS and MET complex dispersions and particles were formulated and analysed using ITC, DSC, XRPD, ATR-FTIR, SEM/EDX, digital microscopy and 2D-SAXS. The calorimetric results confirmed the binding between MET and MAS at various pHs (5, 7 and 9) and temperatures (25 ºC and 37 ºC). The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy, implying that the binding was an enthalpically driven process. These findings suggest that the binding process was dominated by hydrogen bonding and electrostatic interactions. pH and temperature variation did not have a great impact on the binding, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG), with the reaction being only slightly more exothermic at pH 5 and at 37 ºC. 2D-SAXS was able to differentiate between MAS particulates and MAS-MET complexes when analysed in their liquid form suggesting the importance of appropriate methodology and instrumentation used in characterisation. ITC was successfully used in understanding the complexation process occurring between MAS and MET. Care and consideration however should thus be taken in the accurate determination and characterisation techniques for the formation of complexes for controlled release using MAS.

A dual functional superparamagnetic system with pH-dependent drug release and hyperthermia potential for chemotherapeutic applications

A biodegradable, dual functional drug delivery system with superparamagnetic property (Ms: 50.1 emu g−1) for magnetic hyperthermia and tumour-specific pH-dependent drug delivery (loading capacity: 58 μg mg−1) has been designed with magnetically modulated nanocellulose. Increased site-specific bioavailability, effective magnetic hyperthermia potential and pH-responsive controlled release of Doxorubicin (Dox) have been accomplished with a single system, and hence, it is proposed as a multimodal therapeutic tool.

Expanding the Shelf-Life of Ready to use Shredded Icebergs by Using Oxidation - Reduction Potential controlled Release of Various Chlorine Concentrations in Washing Water

Ready to use (RTU) shredded iceberg lettuce is a perishable product with a short shelf-life. Expanding the shelf life to seven days of this product as an economic need for the producers is the aim of this research. Fresh samples were harvested from the field and prepared according to the standard protocol of minimal processing fresh produce (receiving, removing dribs and pre-washing, washing, de-watering, packaging, and storing). Several concentrations of sodium hypochlorite were precisely optimized by oxidative/ reductive Potential (OPR) automated dozing pump under controlled neutral pH and cold temperature during washing regimen. Samples were vacuumed packed and kept tightly sealed at 4 °C for further analysis. Aerobic plate count and coliform as well as sensory evaluation were performed. Results showed that at a chlorine dose level less than 700 mV ORP, the shredded lettuce deteriorated due to elevated microbial load as well as from a sensory point of view. The level of 700 and 800 mV ORP extended shelf life for 7 days. Washing with chlorine levels higher than 800 mV showed alteration in sensory attributes although the microbial load was under control.&#x0D; Results of this study show that the automated ORP chlorine dozing “in form of sodium hypochlorite” at 700 mV (50 ppm) and 800 mV (100 ppm) within controlled pH and temperature, followed by storing the vacuumed well-sealed packs at 4 °C, were the best measures taken to increase the shelf life of the shredded iceberg lettuce from 5 to 7 days. Furthermore, there was no significant difference between the uses of an ORP reading of 700 mV vs. 800 mV of chlorination. However, it is preferable to use the 700 mV ORP reading because it will release less chlorine in the washing water, hence, it will be healthier and more economical.

One-pot fabrication of dual-redox sensitive, stabilized supramolecular nanocontainers for potential programmable drug release using a multifunctional cyclodextrin unit

Facile engineering of β-cyclodextrin (β-CD)-based supramolecular nanocontainers with simultaneous enhanced extracellular stability and efficient intracellular biosignals-triggered destabilization generally suffers from multistep synthesis and tedious purification process, thus remains a significant challenge for the scale-up production and clinical translation of β-CD-based supramolecular nanomedicine. To address these issues, we reported in this study a one-pot preparation of dual-redox sensitive, stabilized supramolecular nanocontainers for potential programmable drug release by self-crosslinking of a multifunctional β-CD unit that integrates a host cavity for oxidation-mediated reversible complexation with ferrocence (Fc) guest molecule and lipoic acids (LAs)-decorated primary and secondary faces for reversible in-situ crosslinking by the reducible disulfide links. The resulting doxorubicin (DOX)-loaded nanoparticles showed, on one hand, enhanced colloidal stability and high DOX loading capacity with a drug loading content (DLC) of approximately 11.3% due to the crosslinked structure, and on the other hand, a programmable destruction of the supramolecular micelles triggered by a simultaneous adoption of intracellular glutathione (GSH) and reactive oxygen species (ROS) toward a complete structural destruction for promoted drug release with enhanced therapeutic efficiency. Notably, an optimized DOX-loaded micelle formation, DOX@CL P1 showed greater cytotoxicity with an IC50 of 2.94 ± 0.25 μg/mL than free DOX (6.00 ± 0.56 μg/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free DOX in L02 normal liver cells. In vivo animal study in Bel-7402 tumor-bearing BALB/c mice further confirmed prolonger elimination half-life time, efficient tumor accumulation, enhanced therapeutic efficiency and compromised systemic toxicity of this micelle construct. Therefore the multifunctional CD unit developed in this study offers an extremely straightforward and robust strategy with respect to dual-redox responsive, stabilized supramolecular nanocontainers with potential programmable controlled release properties for clinical translations.

Fluidized bed spray-coating of enzyme in a cross-linked alginate matrix shell (CLAMshell)

One-step encapsulation of subtilisin by fluidized bed spray-coating in a cross-linked alginate matrix shell (CLAMshell) particle is introduced. The CLAMshell process maximizes process productivity, while simultaneously improving coating quality of spray-coated enzyme. Overall, higher spray rates were achieved with improved mechanical strength of the coating, significantly limiting attrition and suppressing surface damage. Incorporating the CLAMshell formulation improved the overall coating process compared to coatings of cargo-only by achieving a 40% faster spray rate and maintaining coating efficiencies above 90%, with aggregates and fines below 2% of the final product. Process interruptions for removing excessive fines obstructing the outlet filter were eliminated and filter fouling was minimized. Increased alginate content and combination with polyvinyl alcohol in the coating yielded the greatest mechanical strength with low attrition and minor particle damage. CLAMshell particles exhibited high coating integrity through delayed dissolution of the salt core in solution, indicating potential controlled release applications.