ABSTRACT
Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain.
ABSTRACT
Ribavirin has been used as an antiviral agent to treat a variety of viral infections since the 1970s. Over the past few decades, studies have been conducted on the pharmacology of ribavirin, and the possibility of its use in new indications has been explored. According to the results of a number of studies, ribavirin efficacy in the therapy of malignant neoplasms of various genesis has been proven. Furthermore, due to the complexity of brain tumor therapy using surgical methods, targeted delivery of ribavirin to the brain becomes a promising alternative to existing treatment methods. Targeting of active pharmaceutical ingredient (API) to the brain tumor is achieved by intranasal drug delivery via a Nose-to-Brain mechanism. In addition, using this delivery mechanism, it is possible to reach the brain while bypassing the blood-brain barrier (BBB), thus avoiding the effects of the first passage through the liver. Despite the significant advantages of the method, there are limiting factors to its application - mucociliary clearance, which aims to remove foreign bodies from the surface of the nasal mucosa. In situ, systems are able to reduce the intensity of interfering factors on API and allow the achievement of maximum bioavailability during intranasal administration.
ABSTRACT
The rapid growth in the prevalence of infectious diseases requires timely action from drug developers. In recent years, the COVID-19 pandemic has demonstrated the unpreparedness of the population for such emergencies. The introduction of modern methods of Design of Experiments (DoE) is required to accelerate the process of drug development and bring a drug to market. The main objective of this study was to develop an ion-triggered in situ system for intranasal delivery of VLP using a Quality by Design approach. Based on a literature review and initial studies, the key QTPP, CQA, CPP, and CMA were identified to develop a novel delivery system for virus-like particles. As a result of the studies on the quality attributes of the developed delivery system, an ion-triggered in situ gel meeting all the specified parameters was obtained using the Quality by Design method.
ABSTRACT
Implantation is a modern method of administering chemotherapeutic agents, with a highly targeted effect and better patient tolerance due to the low frequency of administration. Implants are capable of controlled release, which makes them a viable alternative to infusional chemotherapy, allowing patients to enjoy a better quality of life without the need for prolonged hospitalization. Compared to subcutaneous implantation, intratumoral implantation has a number of significant advantages in terms of targeting and side effects, but this area of chemotherapy is still poorly understood in terms of clinical trials. At the same time, there are more known developments of drugs in the form of implants and injections for intratumoral administration. The disadvantages of classical intratumoral implants are the need for surgical intervention to install the system and the increased risk of tumor rupture noted by some specialists. The new generation of implants are in situ implants-systems formed in the tumor due to a phase transition (sol-gel transition) under the influence of various stimuli. Among this systems some are highly selective for a certain type of malignant neoplasm. Such systems are injected and have all the advantages of intratumoral injections, but due to the phase transition occurring in situ, they form depot forms that allow the long-term release of chemotherapeutic agents.