Characterizing regional drug delivery within the nasal airways.

INTRODUCTION: The nose has been receiving increased attention as a route for drug delivery. As the site of deposition constitutes the first point of contact of the body with the drug, characterization of the regional deposition of intranasally delivered droplets or particles is paramount to formulation and device design of new products. AREAS COVERED: This review article summarizes the recent literature on intranasal regional drug deposition evaluated in vivo, in vitro and in silico, with the aim of correlating parameters measured in vitro with formulation and device performance. We also highlight the relevance of regional deposition to two emerging applications: nose-to-brain drug delivery and intranasal vaccines. EXPERT OPINION: As in vivo studies of deposition can be costly and time-consuming, researchers have often turned to predictive in vitro and in silico models. Variability in deposition is high due in part to individual differences in nasal geometry, and a complete predictive model of deposition based on spray characteristics remains elusive. Carefully selected or idealized geometries capturing population average deposition can be useful surrogates to in vivo measurements. Continued development of in vitro and in silico models may pave the way for development of less variable and more effective intranasal drug products.

Improved assay development of pharmaceutical modalities using feedback-controlled liquid chromatography optimization.

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.

Recent trends in the delivery of RNA drugs: Beyond the liver, more than vaccine.

RNAs are known for versatile functions and therapeutic utility. They have gained significant interest since the approval of several RNA drugs, including COVID-19 mRNA vaccines and therapeutic agents targeting liver diseases. There are increasing expectations for a new class of RNA drugs for broader applications. Successful development of RNA drugs for new applications hinges on understanding their diverse functions and structures. In this review, we explore the last five years of literature to understand current approaches to formulate a spectrum of RNA drugs, focusing on new efforts to expand their applications beyond vaccines and liver diseases.

"Regulatory Sandboxes" Could Solve the Regulatory Problems Encountered in Europe and Arising from Innovation in Biological Medicinal Products.

Pharmaceutical innovation can sometimes clash with existing regulations, creating challenges for pioneering medicinal products, especially biologics, as they transition from the research phase to product development and post-approval categorisation. For instance, vaccines and advanced therapy medicinal products must fall under the category of biological medicinal products. However, the ability to chemically synthesise both proteins or mRNA can rule out classifying them as vaccines or advanced therapy medicinal products. Consequently, many organic products face regulatory obstacles when attempting to reach the market owing to their inherent natures or involved technologies. The European Commission's proposal for a directive to overhaul the European Union pharmaceutical legislation brings in a new tool: the regulatory sandboxes. They could be a suitable solution to manufacture pioneering medicinal products. Regulatory sandboxes are a form of legal experimentation helping with the marketing of a medicinal product based on groundbreaking technology as they sidestep current regulations. In essence, a regulatory sandbox is a tailor-made, inherently flexible, and time-limited regulatory framework facilitating the development of a drug outside the standard regulatory framework.

The promise of microneedle technologies for drug delivery.

Microneedle (MN) technologies offer the opportunity to improve patient access and target delivery of drugs and vaccines to specific tissues. When in the form of skin patches, MNs can be administered by personnel with minimal training, or could be self-administered by patients, which can improve access to medication, especially those usually requiring injection. Because MNs are small (usually sub-millimetre), they can be used for precise tissue targeting. MN patches have been extensively studied to administer vaccines and drugs in preclinical work as well as in multiple clinical trials. When formulated with biodegradable polymer, MNs can enable long-acting therapies by slowly releasing drug as the MNs biodegrade. Targeted drug delivery by hollow MNs has resulted in FDA-approved products that are able to inject vaccines to skin-resident immune cells to improve immune response and to target specific parts of the eye (e.g., suprachoroidal space) for increased efficacy and avoidance of side effects in other parts of the eye. Cosmetic products based on MN technologies are already in widespread use, mostly as anti-aging agents. With extensive research coupled with FDA-approved products, MN technology promises to continue is growth in research leading to products that can benefit patients.

Pharmaceutical Innovation in Latin America and the Caribbean.

This study assesses Latin America and Caribbean countries' capacity to innovate new pharmaceuticals, defined as developing new drugs and vaccines, repurposing existing drugs, and inventing around patents to produce new drug variations. Vaccine innovation includes reengineering existing vaccines, developing new manufacturing methods, and the clinical development of unapproved vaccine candidates initiated elsewhere.

Trust in pharmaceuticals and vaccine hesitancy: exploring factors influencing COVID-19 immunization among Lebanese children aged 1 to 11 years.

INTRODUCTION: The COVID-19 pandemic is a serious threat to everyone's health. Numerous studies have demonstrated that vaccines are very effective in preventing COVID-19-related severe illness, hospitalization, and death. Children's vaccination exerts its protecting effect by preventing the spread of the virus. The purpose of this study was to analyze the rate of COVID-19 immunization among Lebanese children aged 1 to 11 years and assess parental factors that affect immunization rates. METHODS: An online cross-sectional study was conducted between January and March 2023. The online survey was distributed across all social media channels, including the Ministry of Public Health website. RESULTS: A total of 390 parents filled the survey (mean age = 37.48 ± 8.39 years; 50.5% mothers; 70% with a university level of education). Mothers compared to fathers, having a history of bad reaction to a vaccine vs. not, and higher vaccine hesitancy were significantly associated with less willingness to administer the vaccine to the child. Trusting pharmaceutical companies was significantly associated with more willingness to administer the vaccine to the child. CONCLUSION: The results of this study show that the factors associated with parents' decisions to vaccinate their children may vary. Our findings conclude that vaccine acceptance is being highly associated with parental concerns, trust, and information regarding the vaccine safety and efficacy.

Lyotropic liquid crystalline phases: Drug delivery and biomedical applications.

Liquid crystal (LC)-based nanoformulations may efficiently deliver drugs and therapeutics to targeted biological sites. Lyotropic liquid crystalline phases (LLCPs) have received much interest in recent years due to their unique structural characteristics of both isotropic liquids and crystalline solids. These LLCPs can be utilized as promising drug delivery systems to deliver drugs, proteins, peptides and vaccines because of their improved drug loading, stabilization, and controlled drug release. The effects of molecule shape, microsegregation, and chirality are very important in the formation of liquid crystalline phases (LCPs). Homogenization of self-assembled amphiphilic lipids, water and stabilizers produces LLCPs with different types of mesophases, bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes). Moreover, many studies have also shown higher bioadhesivity and biocompatibility of LCs due to their structural resemblance to biological membranes, thus making them more efficient for targeted drug delivery. In this review, an outline of the engineering aspects of LLCPs and polymer-based LLCPs is summarized. Moreover, it covers parenteral, oral, transdermal delivery and medical imaging of LC in targeting various tissues and is discussed with a scope to design more efficient next-generation novel nanosystems. In addition, a detailed overview of advanced liquid crystal-based drug delivery for vaccines and biomedical applications is reviewed.

On the momentum toward vaccine self-sufficiency in the BRICS: an integrative review of the role of pharmaceutical entrepreneurship and innovation.

Background: With the perspicuous effect of COVID-19 on vaccine demand, academic and business interest in vaccine production in the BRICS nations (Brazil, the Russian Federation, India, China, and South Africa) has reached a crescendo. Aware of a "dark" past when the BRICS depended heavily on vaccines and pharmaceuticals from other parts of the world, academic curiosity on how the BRICS countries have leveraged vaccine self-sufficiency and become the hub of global vaccine production and supply is justifiable, especially in times of ineffable pandemics. Methods: The articles were searched from November 2020 to December 2022. Within this period, an electronic search of 13 reputable healthcare and public databases was conducted. The initial searches from the designated databases yielded a total of 3,928 articles. Then, duplicated studies were removed through a two-step process, articles without titles and abstracts were excluded, and the remaining 898 articles that met the qualification assessment criteria were evaluated for article quality. Results: The main entrepreneurial innovations that have quickened the pace of vaccine self-sufficiency in the BRICS include investment in artificial intelligence (AI), Big Data Analytics, and Blockchain technologies. These help to speed up the drug delivery process by enhancing patient identification or optimizing potential drug candidates for clinical trials and production. Conclusion: Over the past 20 years, the BRICS nations have achieved major strides in vaccine development, regulation, and production. The creation of the BRICS Vaccine Research and Development (R&D) Center will have a significant impact on vaccine cost and accessibility given the anticipated development of stronger research capability, production, and distribution technology, as well as stronger standardization to improve vaccine production quality in the near future. It is anticipated that the BRICS' contributions to vaccine development will alter the global vaccination market and hasten the availability of vaccinations in developing nations. The challenge is turning these hopes into concrete plans of action and outcomes.

Pharma - manufacturing: the unappreciated and overlooked indispensable skill.

The process of vaccine production, manufacturing, is time-intensive, complex, expensive, and highly technical, requiring close coordination and collaboration among multiple companies with different inputs, from active pharmaceutical ingredients to glass, and specializations, and with the supply chains spread across many countries. Covid-19 pandemic highlighted that neglecting and ignoring the need for a global effort in vaccine manufacturing and delivery can have alarming, and devastating, repercussions, especially when the world needs a robust healthcare ecosystem to make sure that all of us are safe. So, the natural question is: what does the world need to be well-prepared for the next virus; what does it take to have the manufacturing of vaccines become less concentrated in a few countries and centers and diversified to more countries so that distribution can be more universal, so that all of us are safe? First will need to be the political recognition, and the acceptance, that no country can do or supply everything alone in the pharmaceutical sector - no country can be an island -and that binding international agreements will need to be adopted to make access to medicine more equitable and secure around the world. Furthermore, and critically so, significant long-term sustained investment in human resources must be adopted to fill major gaps in expertise, starting with a robust educational system whose graduates have the knowledge, ability, and capacity to work in this technical industry. Only then, with a professional-educated labor force, can resilient pharma-manufacturing clusters be successfully built throughout the world, which can, and will, give life to the new health code: "No one is safe, until everyone is safe."

Unraveling the potential of M13 phages in biomedicine: Advancing drug nanodelivery and gene therapy.

M13 phages possessing filamentous phage genomes offer the benefits of selective display of molecular moieties and delivery of therapeutic agent payloads with a tolerable safety profile. M13 phage-displayed technology for resembling antigen portions led to the discovery of mimetic epitopes that applied to antibody-based therapy and could be useful in the design of anticancer vaccines. To date, the excremental experiences have engaged the M13 phage in the development of innovative biosensors for detecting biospecies, biomolecules, and human cells with an acceptable limit of detection. Addressing the emergence of antibiotic-resistant bacteria, M13 phages are potent for packaging the programmed gene editing tools, such as CRISPR/Cas, to target multiple antimicrobial genes. Moreover, their display potential in combination with nanoparticles inspires new approaches for engineering targeted theragnostic platforms targeting multiple cellular biomarkers in vivo. In this review, we present the available data on optimizing the use of bacteriophages with a focus on the to date experiences with M13 phages, either as monoagent or as part of combination regimens in the practices of biosensors, vaccines, bactericidal, modeling of specific antigen epitopes, and phage-guided nanoparticles for drug delivery systems. Despite increasing research interest, a deep understanding of the underlying biological and genetic behaviors of M13 phages is needed to enable the full potential of these bioagents in biomedicine, as discussed here. We also discuss some of the challenges that have thus far limited the development and practical marketing of M13 phages.