In drug delivery systems (DDS), we advocate for a convex acoustic lens-integrated ultrasound (CALUS) as a simple, budget-friendly, and effective replacement for focused ultrasound. The CALUS's characteristics were assessed numerically and experimentally, with a hydrophone as the tool. Within microfluidic channels, microbubbles (MBs) were inactivated in vitro using the CALUS, with adjustable acoustic parameters including pressure (P), pulse repetition frequency (PRF), and duty cycle, alongside varying flow velocities. An in vivo assessment of tumor inhibition was performed in melanoma-bearing mice, measuring tumor growth rate, animal weight, and intratumoral drug concentration in the presence or absence of CALUS DDS. The efficient convergence of US beams, as measured by CALUS, corroborated our simulation results. The microfluidic channel exhibited successful MB destruction at an average flow velocity of up to 96 cm/s, as a result of optimizing acoustic parameters via the CALUS-induced MB destruction test using parameters P = 234 MPa, PRF = 100 kHz, and a duty cycle of 9%. In a murine melanoma model, the in vivo therapeutic effects of doxorubicin, an antitumor drug, were potentiated by the application of CALUS. Combining doxorubicin with CALUS led to a 55% greater decrease in tumor growth compared to doxorubicin alone, strongly suggesting a synergistic effect in the anti-tumor context. Compared to drug-carrier-based methods, our tumor growth inhibition results were superior, despite avoiding the time-consuming and intricate chemical synthesis. This outcome indicates that our innovative, straightforward, economical, and effective target-specific DDS holds promise for transitioning from preclinical studies to clinical trials, and could represent a potential treatment strategy for patient-focused healthcare.
The process of directly administering drugs to the esophagus is hampered by several factors, including the continual dilution of the dosage form by saliva and removal from the tissue surface through esophageal peristalsis. The consequences of these actions are typically short exposure times and lowered drug levels on the esophageal surface, limiting drug absorption into and through the esophageal lining. The potential of diverse bioadhesive polymers to resist removal by salivary washings was examined using an ex vivo porcine esophageal model of porcine esophageal tissue. While hydroxypropylmethylcellulose and carboxymethylcellulose demonstrate bioadhesive qualities, neither polymer formulation proved capable of withstanding repeated salivary contact, causing the gels to detach promptly from the esophageal surface. core biopsy Two polyacrylic polymers, carbomer and polycarbophil, demonstrated a constrained presence on the esophageal surface when rinsed with saliva, potentially stemming from saliva's ionic profile impacting the polymer-polymer interactions pivotal for their elevated viscosity maintenance. Investigations into the potential of in situ gel-forming polysaccharides, triggered by ions, including xanthan gum, gellan gum, and sodium alginate, as local esophageal delivery systems were undertaken. The superior tissue retention properties of these bioadhesive polymers, combined with the anti-inflammatory soft prodrug ciclesonide, were investigated. Treatment of an esophageal segment with ciclesonide-containing gels resulted in therapeutic levels of des-ciclesonide, the active metabolite, in the tissues after a 30-minute period. Esophageal tissue absorption of ciclesonide, as evidenced by increasing des-CIC concentrations, continued throughout the three-hour exposure period. The findings highlight the capability of in situ gel-forming bioadhesive polymer delivery systems to achieve therapeutic drug concentrations within esophageal tissues, thereby promising avenues for localized esophageal disease management.
This study, recognizing the need for more research on inhaler designs, which are crucial to pulmonary drug delivery, explored the influence of various factors, including a unique spiral channel, mouthpiece dimensions (diameter and length), and the gas inlet. An investigation into the impact of inhaler design on performance involved an experimental dispersion study of a carrier-based formulation, in conjunction with computational fluid dynamics (CFD) analysis. Analysis indicates that inhalers equipped with a narrow spiral passageway can enhance the detachment of drug carriers, driven by the introduction of high-velocity, turbulent airflow through the mouthpiece, yet exhibiting substantial drug retention within the device. Studies have shown that diminishing the mouthpiece's diameter and gas inlet size can substantially augment the quantity of fine particles deposited in the lungs, whilst the length of the mouthpiece exhibits a minimal effect on aerosol production. Through the examination of inhaler designs in this study, a more complete comprehension of their significance in relation to overall inhaler performance is developed, and the impact of these designs on the performance of the device is highlighted.
Currently, the dissemination of antimicrobial resistance is spreading at an accelerating pace. As a result, a substantial number of researchers have investigated various alternative therapies in an effort to address this critical problem. moderated mediation Zinc oxide nanoparticles (ZnO NPs), biosynthesized via Cycas circinalis, were examined for their antibacterial properties against Proteus mirabilis clinical isolates in this research project. Chromatographic high-performance liquid analysis was employed for the characterization and precise measurement of C. circinalis metabolites. The green synthesis of ZnO nanoparticles was verified by means of UV-VIS spectrophotometry. Comparative analysis was performed on the Fourier transform infrared spectra of metal oxide bonds and the free C. circinalis extract spectra. An investigation into the crystalline structure and elemental composition was undertaken, utilizing X-ray diffraction and energy-dispersive X-ray techniques. The morphology of nanoparticles was characterized by scanning and transmission electron microscopy, resulting in an average particle size of 2683 ± 587 nm. Spherical shapes were observed. Dynamic light scattering analysis conclusively proves the ideal stability of ZnO nanoparticles, indicated by a zeta potential of 264,049 mV. The antibacterial activity of ZnO nanoparticles in vitro was investigated using agar well diffusion and broth microdilution procedures. Zinc oxide nanoparticles' (ZnO NPs) minimum inhibitory concentrations (MICs) demonstrated a spectrum from 32 to 128 grams per milliliter. Fifty percent of the isolates under examination showed compromised membrane integrity, a consequence of ZnO nanoparticles' action. Subsequently, we determined the in vivo antibacterial activity of ZnO nanoparticles by inducing a systemic infection with *P. mirabilis* in a mouse model. Kidney tissue bacterial counts were performed, indicating a substantial reduction in colony-forming units per gram of tissue sample. Following treatment with ZnO NPs, the survival rate was determined to be higher in the treated group. Histopathological examination of kidney tissues subjected to ZnO nanoparticle treatment demonstrated the presence of normal structures and architecture. Furthermore, immunohistochemical analyses and ELISA assays demonstrated that ZnO nanoparticles significantly reduced the pro-inflammatory mediators NF-κB, COX-2, TNF-α, IL-6, and IL-1β within kidney tissue samples. Finally, the results obtained from this study imply that ZnO nanoparticles effectively combat bacterial infections originating from Proteus mirabilis.
Multifunctional nanocomposite materials have the potential to eliminate tumors entirely and, therefore, prevent tumor recurrence. The A-P-I-D nanocomposite, which is a polydopamine (PDA)-based gold nanoblackbodies (AuNBs) complex loaded with indocyanine green (ICG) and doxorubicin (DOX), underwent investigation for multimodal plasmonic photothermal-photodynamic-chemotherapy. The application of near-infrared (NIR) light to the A-P-I-D nanocomposite resulted in an elevated photothermal conversion efficiency of 692%, surpassing the 629% efficiency of bare AuNBs. The inclusion of ICG, along with a rise in ROS (1O2) generation and improved DOX release, is responsible for this heightened performance. A-P-I-D nanocomposite's assessment on breast cancer (MCF-7) and melanoma (B16F10) cell viability showed considerably reduced cell counts (455% and 24%, respectively) when contrasted with AuNBs' figures of 793% and 768%, respectively. Stained cell fluorescence images exhibited telltale signs of apoptosis in cells treated with the A-P-I-D nanocomposite and near-infrared light, revealing nearly complete damage. Through the use of breast tumor-tissue mimicking phantoms, the A-P-I-D nanocomposite's photothermal performance was evaluated, demonstrating sufficient thermal ablation temperatures within the tumor, while also offering the prospect of eliminating residual cancerous cells through a combined photodynamic and chemotherapy approach. This study's findings suggest that the A-P-I-D nanocomposite, coupled with near-infrared irradiation, yields superior therapeutic efficacy on cell lines and heightened photothermal activity within breast tumor-tissue mimicking phantoms, positioning it as a promising candidate for multimodal cancer treatment.
The self-assembly of metal ions or metal clusters results in the creation of porous network structures, known as nanometal-organic frameworks (NMOFs). Recognized for their unique structural properties, including their porous and flexible structures, large surface areas, surface modifiability, and their non-toxic, biodegradable nature, NMOFs are considered a promising nano-drug delivery system. During the process of in vivo delivery, NMOFs are confronted with a complex and intricate environment. selleck chemicals llc Therefore, the modification of NMOF surfaces is paramount for ensuring the stability of NMOF structure during delivery, overcoming physiological roadblocks for targeted drug delivery, and enabling a controlled release mechanism. The first portion of this review details the physiological hurdles NMOFs overcome during drug delivery via intravenous and oral routes. This section summarizes current drug loading methods into NMOFs, which chiefly involve pore adsorption, surface attachment, the formation of covalent or coordination bonds between drugs and NMOFs, and in situ encapsulation. This paper's third section serves as the primary review, focusing on surface modification strategies for NMOFs in recent years. These methods address physiological barriers to achieve effective drug delivery and disease therapy, broadly categorized as physical and chemical modifications.