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Journal of Nanobiotechnology Jun 2024Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant...
Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.
Topics: Tissue Engineering; Animals; Tissue Scaffolds; Anisotropy; Rats; Rats, Sprague-Dawley; Heart Valves; Hydrogels; Biocompatible Materials; Heart Valve Prosthesis; Polyesters; Cells, Cultured; Humans; Extracellular Matrix; Male
PubMed: 38943185
DOI: 10.1186/s12951-024-02656-5 -
Journal of Nanobiotechnology Jun 2024Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and... (Review)
Review
Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.
Topics: Nanoparticles; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; Lipids; T-Lymphocytes; Neoplasms; Liposomes
PubMed: 38943167
DOI: 10.1186/s12951-024-02630-1 -
Scientific Reports Jun 2024Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and...
Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and absorption thus resulting in low bioavailability. To overcome these drawbacks of OBB, amorphous spray-dried powders (ASDs) of OBB were formulated. The dissolution, characterizations, and pharmacokinetics of OBB-ASDs formulation were investigated, and its hepatoprotective action was disquisitive in the D-GalN/LPS-induced acute liver injury (ALI) mouse model. The characterizations of OBB-ASDs indicated that the crystalline form of OBB active pharmaceutical ingredients (API) was changed into an amorphous form in OBB-ASDs. More importantly, OBB-ASDs showed a higher bioavailability than OBB API. In addition, OBB-ASDs treatment restored abnormal histopathological changes, improved liver functions, and relieved hepatic inflammatory mediators and oxidative stress in ALI mice. The spray drying techniques produced an amorphous form of OBB, which could significantly enhance the bioavailability and exhibit excellent hepatoprotective effects, indicating that the OBB-ASDs can exhibit further potential in hepatoprotective drug delivery systems. Our results provide guidance for improving the bioavailability and pharmacological activities of other compounds, especially insoluble natural compounds. Meanwhile, the successful development of OBB-ASDs could shed new light on the research process of poorly soluble medicine.
Topics: Animals; Toll-Like Receptor 4; Mice; Biological Availability; Berberine; Male; Solubility; Liver; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Oxidative Stress; Protective Agents; Lipopolysaccharides; Powders; Drug Delivery Systems
PubMed: 38942824
DOI: 10.1038/s41598-024-65190-2 -
Progress in Molecular Biology and... 2024Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation,... (Review)
Review
Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.
Topics: Drug Repositioning; Humans; Bacterial Infections; Animals; Anti-Bacterial Agents
PubMed: 38942533
DOI: 10.1016/bs.pmbts.2024.03.031 -
Journal of AOAC International Jun 2024The formation of charge transfer complexes (CTCs) of iodine with five chemotherapeutic drugs used for the treatment of different types of cancer has not been...
BACKGROUND
The formation of charge transfer complexes (CTCs) of iodine with five chemotherapeutic drugs used for the treatment of different types of cancer has not been investigated. These drugs were olaparib, seliciclib, vandetanib, dasatinib, and tozasertib. Additionally, these drugs need an appropriate general spectrophotometric assay for their analysis in the dosage forms regardless of the differences in their chemical structures.
OBJECTIVE
The aim of this study was the development of a novel microwell spectrophotometric assay (MW-SPA) for one-step determination of these drugs via their intereactions with iodine resulted in instantaneous producing a bright lemon yellow-colored CTCs.
METHODS
The spectrophotometric study of the CTCs were conducted, and all CTCs were characterized. Site(s) of interaction on each drug were assigned, and the MW-SPA was developed and applied to the analysis of dosage forms.
RESULTS
The findings confirmed that the reactions proceeded via CTCs formation. Beer's law was obeyed over a general concentration range of 1-6 µg/mL. The limits of detection and quantitation were in the ranges of 0.5-2.1 and 1.5-6.4 µg/mL, respectively. The proposed MW-SPA demonstrated excellent precisions as the relative standard deviations were < 2.24 and 2.23% for the intra- and inter-assay precision, respectively. Recovery studies demonstrated the accuracy of MW-SPA. Successful determination of all drugs in bulk and tablet forms was achieved using the MW-SPA. The environmental sustainability of the proposed methodology was determined, providing evidence of the assay's alignment with the basis of green analytical chemistry. The high throughput of the assay was documented.
CONCLUSIONS
In contrast to other existing methods, the MW-SPA described herein valid for analyzing all drugs at the same wavelength.
HIGHLIGHTS
The assay is useful for routine analysis of drugs in their formulations in quality control laboratories.
PubMed: 38941505
DOI: 10.1093/jaoacint/qsae052 -
International Journal of Molecular... Aug 2024Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second...
Osteosarcoma (OS) is a highly malignant primary bone neoplasm that is the leading cause of cancer‑associated death in young people. GNE‑477 belongs to the second generation of mTOR inhibitors and possesses promising potential in the treatment of OS but dose tolerance and drug toxicity limit its development and utilization. The present study aimed to prepare a novel HO stimulus‑responsive dodecanoic acid (DA)‑phenylborate ester‑dextran (DA‑B‑DEX) polymeric micelle delivery system for GNE‑477 and evaluate its efficacy. The polymer micelles were characterized by morphology, size and critical micelle concentration. The GNE‑477 loaded DA‑B‑DEX (GNE‑477@DBD) tumor‑targeting drug delivery system was established and the release of GNE‑477 was measured. The cellular uptake of GNE‑477@DBD by three OS cell lines (MG‑63, U2OS and 143B cells) was analyzed utilizing a fluorescent tracer technique. The hydroxylated DA‑B was successfully grafted onto dextran at a grafting rate of 3%, suitable for forming amphiphilic micelles. Following exposure to HO, the DA‑B‑DEX micelles ruptured and released the drug rapidly, leading to increased uptake of GNE‑477@DBD by cells with sustained release of GNE‑477. The experiments, including MTT assay, flow cytometry, western blotting and RT‑qPCR, demonstrated that GNE‑477@DBD inhibited tumor cell viability, arrested cell cycle in G1 phase, induced apoptosis and blocked the PI3K/Akt/mTOR cascade response. , through the observation of mice tumor growth and the results of H&E staining, the GNE‑477@DBD group exhibited more positive therapeutic outcomes than the free drug group with almost no adverse effects on other organs. In conclusion, HO‑responsive DA‑B‑DEX presents a promising delivery system for hydrophobic anti‑tumor drugs for OS therapy.
Topics: Animals; Humans; Micelles; Osteosarcoma; Hydrogen Peroxide; Cell Line, Tumor; Dextrans; Mice; Lauric Acids; Apoptosis; Polymers; Xenograft Model Antitumor Assays; Bone Neoplasms; Mice, Nude; Antineoplastic Agents; Mice, Inbred BALB C; Male; TOR Serine-Threonine Kinases
PubMed: 38940336
DOI: 10.3892/ijmm.2024.5393 -
AAPS PharmSciTech Jun 2024Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly...
Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.
Topics: Sitosterols; Animals; Chitosan; Drug Carriers; Particle Size; Burns; Drug Liberation; Wound Healing; Male; Drug Delivery Systems; Rats; Poloxamer; Hydrophobic and Hydrophilic Interactions; Nanostructures; Administration, Topical
PubMed: 38937387
DOI: 10.1208/s12249-024-02852-4 -
European Journal of Pharmaceutics and... Jun 2024Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children's acceptability of compounded preparations and to...
Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children's acceptability of compounded preparations and to provide information regarding compounding practices' characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children's first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as "easy/very easy" to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.
PubMed: 38936783
DOI: 10.1016/j.ejpb.2024.114383 -
Journal of Controlled Release :... Jun 2024In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to...
In vitro-In vivo correlation (IVIVC) is a main focus of the pharmaceutical industry, academia and the regulatory sectors, as this is an effective modelling tool to predict drug product in vivo performance based on in vitro release data and serve as a surrogate for bioequivalence studies, significantly reducing the need for clinical studies. Till now, IVIVCs have not been successfully developed for in situ forming implants due to the significantly different in vitro and in vivo drug release profiles that are typically achieved for these dosage forms. This is not unexpected considering the unique complexity of the drug release mechanisms of these products. Using risperidone in situ forming implants as a model, the current work focuses on: 1) identification of critical attributes of in vitro release testing methods that may contribute to differences in in vitro and in vivo drug release from in situ forming implants; and 2) optimization of the in vitro release method, with the aim of developing Level A IVIVCs for risperidone implants. Dissolution methods based on a novel Teflon shape controlling adapter along with a water non-dissolvable glass fiber membrane (GF/F) instead of a water dissolvable PVA film (named as GF/F-Teflon adapter and PVA-Teflon adapter, respectively), and an in-house fabricated Glass slide adapter were used to investigate the impact of: the surface-to-volume ratio, water uptake ratio, phase separation rate (measured by NMP release in 24 h post injection in vitro or in vivo), and mechanical pressure on the drug release patterns. The surface-to-volume ratio and water uptake were shown to be more critical in vitro release testing method attributes compared to the phase separation rate and mechanical pressure. The Glass slide adapter-based dissolution method, which allowed for the formation of depots with bio-mimicking surface-to-volume ratios and sufficient water uptake, has the ability to generate bio-relevant degradation profiles as well as in vitro release profiles for risperidone implants. For the first time, a Level A IVIVC (rabbit model) has been successfully developed for in situ forming implants. Release data for implant formulations with slightly different PLGA molecular weights (MWs) were used to develop the IVIVC. The predictability of the model passed external validation using the reference listed drug (RLD), Perseris®. IVIVC could not be developed when formulations with different PLGA molar ratios of lactic acid to glycolic acid (L/G) were included. The present work provides a comprehensive understanding of the impact of the testing method attributes on drug release from in situ forming implants, which is a valuable practice for level A IVIVC development.
PubMed: 38936743
DOI: 10.1016/j.jconrel.2024.06.058 -
Indian Journal of Dental Research :... Jan 2024To comparatively evaluate the effect of normal saline gel and ozonated saline-ozonated gel (ozone therapy) on pain, inflammation, soft tissue, and crestal bone loss in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
AIMS
To comparatively evaluate the effect of normal saline gel and ozonated saline-ozonated gel (ozone therapy) on pain, inflammation, soft tissue, and crestal bone loss in dental implant surgery.
METHODS AND MATERIAL
Forty adult patients scheduled to undergo implant were randomized into two groups: Twenty patients (n = 20) received ozone therapy and controls (n = 20) received normal saline and gel during implant placement. Inflammation and pain were noted at days 1 and 7 and 3 month intervals by estimating C-reactive protein (CRP) levels and assessing visual analogue scale (VAS) scores. At 3 months, soft tissue outcomes were noted in terms of plaque index, gingival index, and pocket depth, while crestal bone loss was noted via a radiograph.
RESULTS
Mean CRP levels were significantly higher in the control group as compared to that in the case group on day 1 and day 7 follow-ups (P < 0.05). Mean VAS scores for pain were also lower in the case group as compared to the control group at all follow-ups, but the difference was significant statistically only at day 1 (P = 0.061). The plaque index was significantly lower in the case group as compared to the control group (P = 0.011) at final follow-up. No significant difference between two groups was observed for crestal bone loss.
CONCLUSIONS
Ozone therapy during implant placement was effective in reduction of pain, systemic inflammation, and plaque deposition in dental implant patients.
Topics: Humans; Ozone; Gels; Male; Female; Adult; Middle Aged; C-Reactive Protein; Saline Solution; Dental Implants; Dental Plaque Index; Alveolar Bone Loss; Periodontal Index; Pain Measurement; Dental Implantation; Inflammation
PubMed: 38934740
DOI: 10.4103/ijdr.ijdr_591_23