Gas-stabilizing nanoparticles for ultrasound imaging and therapy of cancer

The use of ultrasound in the clinic has been long established for cancer detection and image-guided tissue biopsies. In addition, ultrasound-based methods have been widely explored to develop more effective cancer therapies such as localized drug delivery, sonodynamic therapy, and focused ultrasound surgery. Stabilized fluorocarbon microbubbles have been in use as contrast agents for ultrasound imaging in the clinic for several decades. It is also known that microbubble cavitation could generate thermal, mechanical, and chemical effects in the tissue to improve ultrasound-based therapies. However, the large size, poor stability, and short-term cavitation activity of microbubbles limit their applications in cancer imaging and therapy. This review will focus on an alternative type of ultrasound responsive material; gas-stabilizing nanoparticles, which can address the limitations of microbubbles with their nanoscale size, robustness, and high cavitation activity. This review will be of interest to researchers who wish to explore new agents to develop improved methods for molecular ultrasound imaging and therapy of cancer.

A Concise Overview on Recent Advances in Pharmaceutical Aerosols and Their Commercial Applications

Background: Localized drug delivery to the respiratory system has become an increasingly successful and essential treatment strategy for several pulmonary diseases, including asthma, chronic abstractive disease, pneumonia, bronchitis, and cystic fibrosis. The rising incidence of respiratory diseases is a significant factor driving the worldwide market for respiratory inhaler devices. Objective: The objective of this article is to present various aspects of pharmaceutical aerosols, including their types, components, fundamentals, in-process and finished product quality control tests based on pharmacopeial standards and specifications, and commercial utility considering the pharmaceutical aerosol dosage forms that have been patented from 2000 to 2020, along with a list of marketed pharmaceutical products. Method: Aerosol, collectively referred to as a pressurized device, operates by triggering an appropriate valve system with a continuous or metered dosage of tiny mist spray. It is used not only in the treatment of asthma and chronic obstructive pulmonary disease but also in the treatment of cancer, diabetes, migraine, angina pectoris, acute lung injury, bone disorders, tuberculosis, and many more. A multitude of different variables, including types and properties of propellants, active substances, containers, valves, actuators, spray patterns, valve crimping efficiency, and particle size of the aerosols, influence the therapeutic effectiveness of pharmaceutical aerosols. Conclusion: Based on the current findings, distinct characteristics such as the elimination of firstpass metabolism, quick drug absorption, ease of therapy termination, as well as a larger surface area have attributed to the success of pharmaceutical aerosols.

Electrochemical bioelectronics in drug delivery - effect of the initial gas volume

Implantable bioelectronic devices with drug delivery capabilities have emerged as suitable candidates for biomedical applications focusing on localized drug delivery. These classes of miniaturized bioelectronics offer wireless operation and refillable designs that can be used for repeated animal behavioral studies without restricting their motion. The pumping mechanisms of these bioelectronic devices features soft materials, microfluidics, and electrochemical subsystems that can be scaled from behavioral studies in small animals to delivery of life-saving medication in humans. Here, we study the refillable aspect of these bioelectronic systems using an analytic model for the drug delivery time established from the ideal gas law when an initial gas volume is present in the device electrolyte reservoirs. The effect of the initial gas volume in delaying the drug delivery time is captured via a non-dimensional parameter identified as the normalized initial gas volume. An analytical solution is derived from the perturbation method, which agrees well with the numerical solution. These results have relevance in the reusability aspect of these bioelectronic systems since modifying the amount of initial gas in the device reservoirs for different experiments affects the total delivery time and can serve as a tunable parameter to ensure timely and successful delivery of the drug in the target region.

Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation

A hydrogel scaffold is a localized drug delivery system that can maintain the therapeutic level of drug concentration at the tumor site. In this study, the biopolymer hydrogel scaffold encapsulating doxorubicin was fabricated from gelatin, sodium carboxymethyl cellulose, and gelatin/sodium carboxymethyl cellulose mixture using a lyophilization technique. The effects of a crosslinker on scaffold morphology and pore size were determined using scanning electron microscopy. The encapsulation efficiency and the release profile of doxorubicin from the hydrogel scaffolds were determined using UV-Vis spectrophotometry. The anti-proliferative effect of the scaffolds against the lung cancer cell line was investigated using an MTT assay. The results showed that scaffolds made from different types of natural polymer had different pore configurations and pore sizes. All scaffolds had high encapsulation efficiency and drug-controlled release profiles. The viability and proliferation of A549 cells, treated with gelatin, gelatin/SCMC, and SCMC scaffolds containing doxorubicin significantly decreased compared with control. These hydrogel scaffolds might provide a promising approach for developing a superior localized drug delivery system to kill lung cancer cells.

Hydrogel-By-Design: Smart Delivery System for Cancer Immunotherapy

Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.

Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin

Thermosensitive chitosan hydrogels—renewable, biocompatible materials—have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (β-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low β-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing β-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.

Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.