Complete Release Research Articles

Scalable spray-dried high-capacity MoC1-x/NC-Li2C2O4 prelithiation composite for lithium-ion batteries

Li2C2O4 is recognized as a promising prelithiation reagent for compensating active lithium owing to its residue-free, high-capacity, air-stable and cost-effective advantages. However, the inherent challenges of low conductivity and high reaction energy barriers necessitate the incorporation of a catalyst to expedite charge conduction and enhance electrochemical activity. It is essential to achieve an efficient composite Li2C2O4 with the catalyst while maintaining substantial prelithiation capacity. Herein, a scalable spray-dried strategy is developed to fabricate MoC1-x/NC-Li2C2O4 composites. The defect-rich nano-MoC1-x/NC catalysis facilitates intimate contact with Li2C2O4, leading to the formation of homogeneous microspheres that promote efficient solid-solid catalysis. Remarkably, the specific capacity of MoC1-x/NC-Li2C2O4 can reach up to 1117 mAh g−1 (calculation based on the complete release of CO2) with a low ratio of catalysts, demonstrating significant application potential. Furthermore, the activation potential of homogeneous MoC1-x/NC-Li2C2O4 composite can be reduced to 4.12 V at 50 °C, while maintaining favorable electrode integrity and wettability. Upon implementation in Gr||NCM622 and SiC||NCM622 full cell, the initial discharge specific capacity is improved by 10.5 % and 11.6 %, respectively. Notably, sufficient active lithium post-prelithiation preserves the cathode and SEI structural stability, ensuring a stable cycling performance. This work presents a scalable prelithiation material with great promise for advanced lithium-ion battery applications.

Construction, characterization and bioactivity evaluation of curcumin nanocrystals with extremely high solubility and dispersion prepared by ultrasound-assisted method

Curcumin (Cur) as a natural pigment and biological component, can be widely used in food and beverages. However, the water insolubility of Cur significantly limits its applications. In this study, we prepared a series of nanocrystals via ultrasound-assisted method to improve the solubility and availability of Cur. The results showed artemisia sphaerocephala krasch polysaccharide (ASKP), gum arabic (GA) and wheat protein (WP) were outstanding stabilizers for nanocryatals except traditional agent, poloxamer 188 (F68). The obtained curcumin nanocrystals (Cur-NC) displayed a rod-shaped, crystal- and nanosized structure, and extremely high loading capacity (more over 80 %, w/w). Compared with raw powder, Cur-NC greatly improved the water solubility and dispersibility, and the slow and complete release of Cur of Cur-NC also endowed them excellent antioxidant capacities even at 10 μg/mL. Importantly, as functional factor additive in beverages (e.g. water and emulsion), Cur-NC could increase the content of Cur to at least 600 μg/mL and retain a good stability. Overall, we provided an effective improvement method for the liposoluble active molecules (e.g. Cur) based on the nanocrystals, which not only tremendously enhanced its water solubility, but also strengthened its bioactivity. Notably, our findings broadened the application of water-insoluble compounds.

Formulation and Development of Novel Sulfasalazine Bilayer Tablets for The Treatment of Arthritis Associated With IBD: In-vitro and In-vivo Investigations

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l-100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems.

Formulation and Evaluation of Indomethacin Sustained Release Tablet by using Natural Polymers

Arthritis is most prevalent disorder and Indomethacin is choice of drug for arthritis. Oral route is most preferred route of drug administration and tablets are the more convenient dosage form. In present research natural polymers guar gum and xanthan gum were used to make sustained release tablet of Indomethacin. Indomethacin release from the tablets was studied in phosphate buffer pH 7.2. The drug release pattern of six different formulations in which xanthan gum and guar gum were used as a retarding material in different proportions was shown in table no. 6. The formulation F1 releases (75.20%) upto 12 hrs whereas the formulation F2 releases the drug (98.81%) in same time. The formulations F3, F4, F5 and F6 release 98.32%, 99.29%, 98.79% and 82.40% respectively. The dissolution pattern of both gums was similar i.e. with drug to polymer ratio (1:1). In present work F1 shows best sustained release upto 12 hrs in which Drug to Polymer ratio was 1:1:0 (Drug : Xanthan gum : Guar gum). In formulation F2 drug release was not sustained and complete release occurs in 12 hrs where the Drug to Polymer ratio was 1:1.67:0 (Drug: Xanthan gum : Guar gum). It was found that on the concentration of xanthan gum decreases the release rate of the drug also decreases. For sustain release there is not much role of Guar Gum reported. Indomethacin drug has been selected which has half-life 4.5 hrs. Hence the present work, an attempt has been made to provide sustained release drug delivery using polymers with Indomethacin as the model drug. Xanthan gum was best able to retard Indomethacin release mechanism even in the presence of a polymer. Polymer can be used to formulate successful sustained release Indomethacin matrix tablets that have desirable characteristics.

Newly modified 'pseudo flap' without compromising vascularity to enhance repair of long distal ureteral loss: A retrospective analysis of a prospective database.

To present an alternative technique called pseudo-flap for reconstructing long ureteral defects as an alternative to Boari flap. Despite being used for more than 70 years by urologists for tension-free reconstruction of distal and mid-ureteral defects, the Boari flap exhibits high complication rates, with an average of 27% (range 5.5%-30.4%). These complications arise from compromised blood supply, attributed to incisions made on all three sides of the flap and dependence on the flap base as the sole source of blood supply. We retrospectively reviewed patients who underwent our modified technique by a single surgeon between 2008 and 2021. We used a semi-oblique cystotomy on the lowest part of the anterior and contralateral aspects of the bladder after complete release from adhesions and sacrificing the superior vesical pedicle, if necessary. The innovative part of the technique involved making short relaxing incisions at different levels on both sides of a pseudo-flap while pushing the bladder dome upward to reach the healthy ureter in a tension-free manner, followed by anastomosis with a non-refluxing or refluxing technique. Fifteen patients underwent the pseudo-flap technique with a mean follow-up of 16.9months. Four had prior radiation, three had hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis, and one had a ureteral stricture in a transplanted kidney. Eight procedures were performed during intraoperative consultations.Only one patient (7%) developed a major complication (Clavien-Dindo grade ≥2). This patient developed postoperative leak, and none developed obstructive hydronephrosis, suggesting stricture or flap ischemia. The mean length of the flap was 9.3cm. Our pseudo-flap technique has lower complication rates than the traditional Boari flap. It is not technically challenging, minimally compromises blood supply and is thus especially suitable for complex, highly morbid patients with decreased tissue vascularity, such as those with prior radiation and peritoneal carcinomatosis.

Functional Hydrogels for Delivery of the Proteolytic Enzyme Serratiopeptidase.

Hydrogels are superior wound dressings because they can provide protection and hydration of the wound, as well as the controlled release of therapeutic substances to aid tissue regeneration and the healing process. Hydrogels obtained from natural precursors are preferred because of their low cost, biocompatibility, and biodegradability. We describe the synthesis of novel functional hydrogels based on two natural products-citric acid (CA) and pentane-1,2,5-triol (PT, a product from lignocellulose processing) and poly(ethylene glycol) (PEG-600)-via an environment friendly approach. The hydrogels were prepared via monomer crosslinking through a polycondensation reaction at an elevated temperature in the absence of any solvent. The reagents were blended at three different compositions with molar ratios of hydroxyl (from PT and PEG) to carboxyl (from CA) groups of 1:1, 1:1.4, and 1.4:1, respectively. The effect of the composition on the physicomechanical properties of materials was investigated. All hydrogels exhibited pH-sensitive behavior, while the swelling degree and elastic modulus were dependent on the composition of the polymer network. The proteolytic enzyme serratiopeptidase (SER) was loaded into a hydrogel via physical absorption as a model drug. The release profile of SER and the effects of the enzyme on healthy skin cells were assessed. The results showed that the hydrogel carrier could provide the complete release of the loaded enzyme.

Nanogel delivery systems for cationic peptides: More than a ‘One Size Fits All’ solution

Self-assembled hyaluronic acid-based nanogels are versatile drug carriers due to their biodegradable nature and gentle preparation conditions, making them particularly interesting for delivery of peptide therapeutics. This study aims to elucidate the relation between peptide structure and encapsulation in a nanogel. Key peptide properties that affect encapsulation in octenyl succinic anhydride-modified hyaluronic acid nanogels were identified as we explored the effect on nanogel characteristics using 12 peptides with varying charge and hydrophobicity. The size and surface properties of the microfluidics-assembled peptide-loaded nanogels were evaluated using dynamic light scattering, laser Doppler electrophoresis, and small angle neutron scattering. Additionally, the change in peptide secondary structure upon encapsulation in nanogels, their release from the nanogels, and the in vitro antimicrobial activity were assessed. In conclusion, the more hydrophobic peptides showed stronger binding to the nanogel carrier and localized internally rather than on the surface of the nanogel, resulting in more spherical nanogels with smoother surfaces and slower release profiles. In contrast, cationic and hydrophilic peptides localized at the nanogel surface resulting in fluffier nanogel structures and quick and more complete release in biorelevant medium. These findings emphasize that the advantages of nanogel delivery systems for different applications depend on the therapeutic peptide properties.

A new fluorocarbon adhesive: Inhibiting agglomeration during combustion of propellant via efficient F–Al2O3 preignition reaction

AbstractInhibiting the agglomeration of molten aluminum particles packed in the binder network is a promising scheme to achieve efficient combustion of solid propellants. In this investigation, the hydroxyl‐terminated structured fluorinated alcohol compound (PFD) was introduced to modify the traditional polyethylene glycol/polytetrahydrofuran block copolymerization (HTPE) binder; that is, a unique fluorinated polyether (FTPE) binder was synthesized by embedding fluorinated organic segments into the HTPE binder via crosslinking curing. The FTPE was applied in aluminum‐based propellants for the first time. Due to the complete release of fluorinated organic active segments in the range of 300°C to 400°C, the burning rate of FTPE‐based propellant increased from 4.07 (0% PFD) to 6.36 mm/s (5% PFD), increased by 56.27% under 1 MPa. The reaction heat of FTPE propellants increased from 5.95 (0% PFD) to 7.18 MJ/kg (5% PFD) under 3.0 MPa, indicating that HTPE binder modified with PFD would be conducive to inhibiting the D90 of condensed combustion products (CCPs) dropped by 81.84% from 75.46 (0% PFD) to 13.71 μm (5% PFD) under 3.0 MPa, in consistent with the significant reduction of aluminum agglomerates observed on the quenched burning surface of the propellants. Those results demonstrated that a novel FTPE binder with PFD can release fluorinated organic active segments, which motivate preignition reaction with the alumina shell in the early stage of aluminum combustion, and then enhance the melting diffusion effect of aluminum to inhibit the agglomeration.

Classification of and individual treatment strategies for complex tethered cord syndrome.

To study the classification, diagnosis, and treatment strategies of complex tethered cord syndrome (C-TCS) on the basis of the patients' clinical symptoms, imaging findings, and therapeutic schedule. The clinical data of 126 patients with C-TCS admitted to our department from January 2015 to December 2020 were retrospectively analyzed. Classification criteria for C-TCS were established by analyzing the causes of C-TCS. Different surgical strategies were adopted for different types of C-TCS. The Kirollos grading, visual analogue scale (VAS), critical muscle strength, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the surgical outcomes and explore individualized diagnosis and treatment strategies for C-TCS. C-TCS was usually attributable to three or more types of tether-causing factors. The disease mechanisms could be categorized as pathological thickening and lipomatosis of the filum terminal (filum terminal type), arachnoid adhesion (arachnoid type), spina bifida with lipomyelomeningocele/meningocele (cele type), spinal lipoma (lipoma type), spinal deformity (bone type), and diastomyelia malformation (diastomyelia type). Patients with different subtypes showed complex and varied symptoms and required individualized treatment strategies. Since C-TCS is attributable to different tether-related factors, C-TCS classification can guide individualized surgical treatment strategies to ensure complete release of the tethered cord and reduce surgical complications.

Biphasic Porous Bijel-Like Structures with Hydrogel Domains as Controlled Drug Delivery Systems.

Bijels are a peculiar type of Pickering emulsion that have a bicontinuous morphology and are stabilised by a jammed layer of nanoparticles (NPs). Due to their double nature, their usage has increased in recent years in various fields, such as biological and food applications. In fact, they can release both hydrophilic and hydrophobic compounds simultaneously. An improvement to this structure is the use of a hydrophobic monomer like polycaprolactone as the organic phase, which is able to polymerise during the formation of the structure. Unfortunately, the structures formed in this way always have some drawbacks, such as their thermal stability or degradation when submerged in an aqueous medium. A number of studies have been carried out in which some parameters, such as the NPs or the monomer, were changed and their effect on the final product evaluated. In this work, the effect of modifying the aqueous phase was studied. In particular, the effect of adding alginate, a biopolymer capable of forming a stable hydrogel in the presence of divalent cations, was analysed, as was the difference between soaking or not in CaCl2, the final system. Specific attention was paid to their swelling behaviour (150% vs. 25% of the blank sample), rheological properties (G' 100 kPa vs. 20 kPa of the blank sample) and their release performances. In this framework, complete release of hydrophilic drug vs. 20% in the blank sample was observed together with improved release of the hydrophobic one with 35% in 8 h vs. 5% in the case of the blank sample. This strategy has been proven to influence bijels' properties, opening the doors to many different uses.

Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

Regulation of the colon-targeted release rate of lactoferrin by constructing hydrophobic ethyl cellulose/pectin composite nanofibrous carrier and its effect on anti-colon cancer activity

In order to modify colonic release behavior of lactoferrin (Lf), a hydrophobic composite nanofibrous carrier (CNC) was constructed by emulsion coaxial electrospinning. Ethylcellulose/pectin based water-in-oil emulsion and Lf-contained polyvinyl alcohol solution were used as shell and core fluids, respectively. An electrospinning diagram was first constructed to screen out suitable viscosity (51–82 cP) and conductivity (960–1300 μS/cm) of the dispersed phase of pectin solution for successful electrospinning of shell emulsion. Varying mass fraction of pectin solution (5 %–20 %) of shell emulsion during emulsion coaxial electrospinning obtained CNCs with different micro-structures, labeled as 5&95 CNC, 10&90 CNC, 15&85 CNC, 20&80 CNC. These CNCs all achieved colonic delivery of Lf (>95 %), and the time for complete release of Lf in simulated colon fermentation process were 10, 7, 5 and 3 h, respectively. That is, the greater the pectin content in CNC, the faster the release rate of stabilized Lf in colon. Lf release in simulated colon fermentation fluid involved complex mechanisms, in which diffusion release of Lf was dominant. Increasing colonic release rate of Lf enhanced its regulation effect on the expression levels of cell cycle arrest and apoptosis-related protein and promote its effective inhibition on the proliferation of HCT116 cell.

Salivary Amylase-Responsive Buccal Tablets Wipe Out Chemotherapy-Rooted Refractory Oral Mucositis.

Oral mucositis (OM) is the most common and refractory complication of cancer chemotherapy and radiotherapy, severely affecting patients' life quality, lowering treatment tolerance, and discouraging patient compliance. Current OM delivery systems mostly affect the comfort of patient use and lead to poor compliance and unsatisfactory effects. Herein, salivary amylases (SAs)-responsive buccal tablets consisting of porous manganese-substituted Prussian blue (PMPB) nanocubes (NCs), anti-inflammatory apremilast (Apr) and starch controller have been engineered. PMPB NCs with large surface area can serve as carriers to load Apr, and their multienzyme-mimicking activity enables them to scavenge reactive oxygen species (ROS), which thus synergize with Apr to mitigate inflammation. More significantly, the starch controller can respond to abundant SAs in the oral cavity and realize the cascade, continuous, and complete drug release after enzymatic decomposition, which not only aids with high tissue affinity to prolong the resistance time but also improves the comfort of use. The preclinical study reveals that contributed by the above actions, such buccal tablets mitigate inflammation, promote endothelium proliferation and migration, and accelerate wound healing for repressing chemotherapy-originated intractable OM with positive oral microenvironment and shorter recovery time, thus holding high potentials in clinical translation.

A Modular Albumin-Oligonucleotide Biomolecular Assembly for Delivery of Antisense Therapeutics.

Antisense nucleic acid drugs are susceptible to nuclease degradation, rapid renal clearance, and short circulatory half-life. In this work, we introduce a modular-based recombinant human albumin-oligonucleotide (rHA-cODN) biomolecular assembly that allows incorporation of a chemically stabilized therapeutic gapmer antisense oligonucleotide (ASO) and FcRn-driven endothelial cellular recycling. A phosphodiester ODN linker (cODN) was conjugated to recombinant human albumin (rHA) using maleimide chemistry, after which a complementary gapmer ASO, targeting ADAMTS5 involved in osteoarthritis pathogenesis, was annealed. The rHA-cODN/ASO biomolecular assembly production, fluorescence labeling, and purity were confirmed using polyacrylamide gel electrophoresis. ASO release was triggered by DNase-mediated degradation of the linker strand, reaching 40% in serum after 72 h, with complete release observed following 30 min of incubation with DNase. Cellular internalization and trafficking of the biomolecular assembly using confocal microscopy in C28/I2 cells showed higher uptake and endosomal localization by increasing incubation time from 4 to 24 h. FcRn-mediated cellular recycling of the assembly was demonstrated in FcRn-expressing human microvascular endothelial cells. ADAMTS5 in vitro silencing efficiency reached 40%, which was comparable to free gapmer after 72 h incubation with human osteoarthritis patients' chondrocytes. This work introduces a versatile biomolecular modular-based "Plug-and-Play" platform potentially applicable for albumin-mediated half-life extension for a range of different types of ODN therapeutics.

Controlled Release Bilayer Floating Effervescent and Noneffervescent Tablets Containing Levofloxacin and Famotidine

The present study is aimed at designing bilayer-floating tablets to improve the drug concentration in the stomach for enhanced therapeutic efficacy. The tablets are comprised of an upper layer of levofloxacin (466.5 mg) and a lower layer of famotidine (133.5 mg). Five formulations (F1-F5) were developed by using hydroxypropyl methylcellulose grades (K4M, K15M, and K100M) along with Carbopol 934. In the case of the effervescent system (F1-F3), sodium bicarbonate was added to impart buoyancy to the tablets; while in the case of noneffervescent formulations (F4 & F5), guar gum and xanthan gum were incorporated to induce flotation and swelling and retard the release of a drug. The precompression characteristics of tablets depict the suitability of all formulation powder for direct compression. The ATR-FTIR analyses have shown that the components of both effervescent and noneffervescent tablets are compatible with each other. The total weight of each tablet was 600 mg, with a weight variation of about ≤10 mg. Both the layers were smooth and flat with a thickness ranging from 3.16±0.04 to 3.54±0.01 mm. The diameters of prepared floating tablets were about 15 mm, optimum for oral administration. After adjusting the tablet’s hardness to 6-7 kg/cm2, its friability was found to be <0.35 percent. The mean drug content of the formulations was above 90%. The floating lag time of all formulations (F2-F5) was below 25 seconds, except F1 which took almost 50 seconds to start floating on the surface of gastric content due to its higher density. The total floating time of effervescent (F1-F3) and noneffervescent formulations was in the range of 15-25 hours, thereby providing sufficient time to complete drug release and absorption in the gastric area. The total floating time of noneffervescent formulations was higher (p≤0.05) than effervescent formulations due to efficient wettability and swelling characteristics. The release of drugs from both layers of noneffervescent tablets was significantly controlled when compared to the effervescent system, and an anomalous non-Fickian diffusion was found for the drug release. The stability study of the optimized formulation proved the integrity and stability of the developed formulation. Thus, developed formulations are deemed suitable for controlled codelivery of active pharmaceutical ingredients for the effective treatment of H. pylori.

3D-Printed Alginate/Pectin-Based Patches Loaded with Olive Leaf Extracts for Wound Healing Applications: Development, Characterization and In Vitro Evaluation of Biological Properties.

Traditional wound dressings may lack suitability for diverse wound types and individual patient requirements. In this context, this study aimed to innovate wound care by developing a 3D-printed patch using alginate and pectin and incorporating Olive Leaf Extract (OLE) as an active ingredient. Different polymer-to-plasticizer ratios were systematically examined to formulate a printable ink with optimal viscosity. The resultant film, enriched with OLE, exhibited a substantial polyphenolic content of 13.15 ± 0.41 mg CAE/g, showcasing significant antioxidant and anti-inflammatory properties. Notably, the film demonstrated potent scavenging abilities against DPPH, ABTS, and NO radicals, with IC50 values of 0.66 ± 0.07, 0.47 ± 0.04, and 2.02 ± 0.14 mg/mL, respectively. In vitro release and diffusion studies were carried out and the release profiles revealed an almost complete release of polyphenols from the patch within 48 h. Additionally, the fabricated film exhibited the capacity to enhance cell motility and accelerate wound healing, evidenced by increased collagen I expression in BJ fibroblast cells. Structural assessments affirmed the ability of the patch to absorb exudates and maintain the optimal moisture balance, while biocompatibility studies underscored its suitability for biomedical applications. These compelling findings endorse the potential application of the developed film in advanced wound care, with the prospect of tailoring patches to individual patient needs.

Electrochemical and Spectroscopic Studies Performed for Indomethacin and 1-Naphthol Incorporated in 1-Butyl-3-methyl-imidazolium Bis(2-ethylhexyl) Sulfosuccinate Vesicles to Investigate Them as a Potentially pH-Sensitive Nanocarrier.

Characterization studies of 1-butyl-3-methyl-imidazolium bis(2-ethylhexyl) sulfosuccinate vesicles at different pH values have been carried out by using liquid surface tension, transmission electron microscopy, and dynamic light scattering. The results show that there are no vesicle changes in its size and negative Z potential at pH 3, 6, and 10. Furthermore, indomethacin and 1-naphthol, both pH-dependent, electroactive, and fluorescence probes, were used to further characterize the bilayer employing electrochemical and emission techniques. The partition of indomethacin and 1-naphthol between the water and bilayer pseudophases only occurs for the neutral species and does not happen for the anionic species because the highly negative Z bilayer potential prevents incorporation due to negative repulsion. For the neutral species, the partition constant values were evaluated by square wave voltammetry and emission spectroscopy. Finally, for the indomethacin incorporated into the vesicle bilayer at pH 3, the release profile was monitored over time at pH 6. It was found that a change in the pH values causes the complete release of indomethacin after 25 min, which led us to think that the vesicles presented in this work can be used as a pH-sensitive nanocarrier for neutral pH-sensitive drugs.

Printing a cure: A tailored solution for localized drug delivery in liver cancer treatment

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy.

TRANSFECTION OF HMSCS WITH CHEMICALLY MODIFIED MRNA CODING FOR BMP-7 ENHANCES OSTEOGENESIS

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production.1 The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use.2 Furthermore, BMP-7 was removed from the market.3 These complications are related to the high doses used (1.5-40 miligrams per surgery)2 compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range).4 In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones.5 Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA.6 BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration.Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790.

Characterization of chitosan- and β-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.

An advanced form of magnesium-rich hydroxyapatite (Mg·HAP) was modified with two types of biopolymers, namely chitosan (CH/Mg·HAP) and β-cyclodextrin (CD/Mg·HAP), producing two types of bio-composites. The synthesized materials were developed as enhanced carriers for levofloxacin to control its loading, release, and anti-inflammatory properties. The polymeric modification significantly improved the loading efficiency to 281.4 mg g-1 for CH/Mg·HAP and 332.4 mg g-1 for CD/Mg·HAP compared with 218.3 mg g-1 for Mg·HAP. The loading behaviors were determined using conventional kinetic and isotherm models and mathematical parameters of new equilibrium models (the monolayer model of one energy). The estimated density of effective loading sites (Nm (LVX) = 88.03 mg g-1 (Mg·HAP), 115.8 mg g-1 (CH/Mg·HAP), and 138.5 mg g-1 (CD/Mg·HAP)) illustrates the markedly higher loading performance of the modified forms of Mg·HAP. Moreover, the loading energies (<40 kJ mol-1) in conjunction with the capacity of each loading site (n > 1) and Gaussian energies (<8 kJ mol-1) signify the physical trapping of LVX molecules in vertical orientation. The addressed materials validate prolonged and continuous release behaviors. These behaviors accelerated after the modification procedures, as the complete release was identified after 160 h (CH/Mg·HAP) and 200 h (CD/Mg·HAP). The releasing behaviors are regulated by both diffusion and erosion mechanisms, according to the kinetic investigations and diffusion exponent analysis (>0.45). The entrapping of LVX into Mg·HAP induces its anti-inflammatory properties against the generation of cytokines (IL-6 and IL-8) in human bronchial epithelia cells (NL20), and this effect displays further enhancement after the integration of chitosan and β-cyclodextrin.