Recent Advances in Drug Delivery and Formulation - Volume 16, Issue 2, 2022

The term "reactive oxygen species" (ROS) refers to a family of extremely reactive molecules. They are crucial as secondary messengers in both physiological functioning and the development of cancer. Tumors have developed the ability to survive at elevated ROS levels with significantly higher H2O2 levels than normal tissues. Chemodynamic therapy is a novel approach to cancer treatment that generates highly toxic hydroxyl radicals via a Fenton/Fenton-like reaction between metals and peroxides. Inorganic nanoparticles cause cytotoxicity by releasing ROS. Inorganic nanoparticles can alter redox homoeostasis by generating ROS or diminishing scavenging mechanisms. Internalized nanoparticles generate ROS in biological systems independent of the route of internalisation. This method of producing ROS could be employed to kill cancer cells as a therapeutic strategy. ROS also play a role in regulating the development of normal stem cells, as excessive ROS disturb the stem cells' regular biological cycles. ROS treatment has a significant effect on normal cellular function. Mitochondrial ROS are at the centre of metabolic changes and control a variety of other cellular processes, which can lead to medication resistance in cancer patients. As a result, utilising ROS in therapeutic applications can be a double-edged sword that requires better understanding.

Nowadays, the development of mucoadhesive systems for drug delivery has gained keen interest, with enormous potential in applications through different routes. Mucoadhesion characterizes an attractive interaction between the pharmaceutical dosage form and the mucosal surface. Many polymers have shown the ability to interact with mucus, increasing the residence time of local and/or systemic administered preparations, such as tablets, patches, semi-solids, and micro and nanoparticles. Cellulose is the most abundant polymer on the earth. It is widely used in the pharmaceutical industry as an inert pharmaceutical ingredient, mainly in its covalently modified forms: methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose salts. Aiming to overcome the drawbacks of oral, ocular, nasal, vaginal, and rectal routes and thereby maintaining patient compliance, innovative polymer blends have gained the interest of the pharmaceutical industry. Combining mucoadhesive and thermoresponsive polymers allows for simultaneous in situ gelation and mucoadhesion, thus enhancing the retention of the system at the site of administration and drug availability. Thermoresponsive polymers have the ability to change physicochemical properties triggered by temperature, which is particularly interesting considering the physiological temperature. The present review provides an analysis of the main characteristics and applications of cellulose derivatives as mucoadhesive polymers and their use in blends together with thermoresponsive polymers, aiming at platforms for drug delivery. Patents were reviewed, categorized, and discussed, focusing on the applications and pharmaceutical dosage forms using this innovative strategy. This review manuscript also provides a detailed introduction to the topic and a perspective on further developments.

Vaccines are one of the greatest medical achievements of modern medicine. The nasal mucosa represents an effective route of vaccination for both mucosal immunity and peripheral, being at the same time an inductive and effector site of immunity. In this paper, the innovative and patented compositions and manufacturing procedures of nanomaterials have been studied using the peerreviewed research literature. Nanomaterials have several properties that make them unique as adjuvant for vaccines. Nanoadjuvants through the influence of antigen availability over time affect the immune response. Namely, the amount of antigen reaching the immune system or its release over prolonged periods of time can be effectively increased by nanoadjuvants. Mucosal vaccines are an interesting alternative for immunization of diseases in which pathogens access the body through these epithelia. Nanometric adjuvants are not only a viable approach to improve the efficacy of nasal vaccines but in most of the cases they represent the core of the intellectual property related to the innovative vaccine.

Background: Transfersomes can be used to enhance transdermal drug delivery due to their flexibility and ability to incorporate various molecules. For example, hydrocortisone (HC), a corticosteroid, is taken by different routes and serves as immunosuppressive, anticancer, and antiallergenic; however, it is poorly absorbed by the skin. Objective: Therefore, the current study suggested HC-loaded transfersomes as an alternative route of administration for reaching deeper skin layers or systemic circulation, to reduce the side effects of HC and improve its bioavailability. Methods: HC transfersomes were prepared by the thin-film hydration method and characterized for their vesicular size, zeta potential, drug entrapment efficiency, elasticity, FTIR spectroscopy, in vitro drug release, ex vivo permeation, and irritancy in rabbits. The optimized formulation, F15 (containing HC 20 mg, egg phosphatidylcholine (EPC) 400 mg, and 75 mg of Span 80), was chosen because it showed the highest (p< 0.05) EE% (60.4±0.80) and optimized sustained in vitro drug release (Q8 = 87.9±0.6%). Results: Extensive analysis of the drug release data from all formulas was performed using the DDSolver software which quantitatively confirmed the successful formulation. The Weibull equation was the best model to fit the release data compared to others, and the release mechanism was Fickian diffusion. Conclusion: The simulated pharmacokinetic parameters showed that F15 had the highest AUC, MDT, and DE. Furthermore, F15 significantly enhanced HC permeation by 12-folds compared to the control through the excised rat's skin. The skin irritancy test has proven F15 safety and skin compatibility.

Background: This paper provides a comprehensive overview of the patent situation for hydrogel- based bioinks used for 3D bioprinting globally. It encapsulates information which could be used as a reference by researchers in the fields of 3D bioprinting, biomaterials, tissue engineering, and biomedical engineering, as well as those interested in biomaterials, especially in the formulation of hydrogels. It can also inform policy discussions, strategic research planning, or technology transfer in this area. The findings presented hereinafter are considered novel research aspects regarding the used hydrogels, their preparation methods, and their formulations, as well as the 3D bioprinting process using hydrogels. Furthermore, the novel part, synthesized patents, is regarded as a breakthrough in hydrogel- based bioinks. Methods: The following research aspects of this study are based on data collection from selected patent databases. The search results are then analyzed according to publication years, classification, inventors, applicants, and owners, as well as jurisdictions. Results: Based on the earliest priority date, it is possible to precisely assume that 2004 is considered the starting year of patenting of hydrogel-based bioinks. Furthermore, 2020 was the year with the most patent documents. According to the findings, the United States, China, and the Republic of Korea are the most prolific countries in terms of patenting on hydrogel-based bioinks. The most prolific patenting companies are from the United States, Sweden, and Australia, while universities from the Republic of Korea and the United States are the academic institutions leading the way. Most inventions of hydrogel- based bioinks intended for hydrogels or hydrocolloids used as materials for prostheses or for coating prostheses are characterized by their function or physical properties. Conclusion: The state has been reviewed by introducing what has been patented concerning hydrogelbased bioinks. Knowledge clusters and expert driving factors indicate that the research based on biomaterials, tissue engineering, and biofabrication is concentrated in the most common patent documents. Finally, this paper, which gives a competitive analysis of the past, present, and future trends in hydrogel-based bioinks, leads to various recommendations that could help one to plan and innovate research strategies.