Patient Centricity Driving Formulation Innovation: Improvements in Patient Care Facilitated by Novel Therapeutics and Drug Delivery Technologies.

Innovative formulation technologies can play a crucial role in transforming a novel molecule to a medicine that significantly enhances patients' lives. Improved mechanistic understanding of diseases has inspired researchers to expand the druggable space using new therapeutic modalities such as interfering RNA, protein degraders, and novel formats of monoclonal antibodies. Sophisticated formulation strategies are needed to deliver the drugs to their sites of action and to achieve patient centricity, exemplified by messenger RNA vaccines and oral peptides. Moreover, access to medical information via digital platforms has resulted in better-informed patient groups that are requesting consideration of their needs during drug development. This request is consistent with health authority efforts to upgrade their regulations to advance age-appropriate product development for patients. This review describes formulation innovations contributingto improvements in patient care: convenience of administration, preferred route of administration, reducing dosing burden, and achieving targeted delivery of new modalities.

Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR expression and translational responses. Crucially, the link between NK cell biology and design of drug delivery technologies are made, which is essential for development of future non-viral approaches. This review provides valuable insights into the current state of non-viral CAR-NK cell engineering, aimed at realising the full potential of NK cell-based immunotherapies.

An overview on recent approaches for colonic drug delivery systems.

Colon-targeted drug delivery systems have garnered significant interest as potential solutions for delivering various medications susceptible to acidic and catalytic degradation in the gastrointestinal (GI) tract or as a means of treating colonic diseases naturally with fewer overall side effects. The increasing demand for patient-friendly drug administration underscores the importance of colonic drug delivery, particularly through noninvasive methods like nanoparticulate drug delivery technologies. Such systems offer improved patient compliance, cost reduction, and therapeutic advantages. This study places particular emphasis on formulations and discusses recent advancements in various methods for designing colon-targeted drug delivery systems and their medicinal applications.

A systematic review of emerging technologies to enhance the treatment of ovarian cancer.

The efficacy and safety of chemotherapy are two major challenges when it comes to treating ovarian cancer. The associated undesirable side effects of chemotherapy agents jeopardize the clinical intent and the efficiency of the therapy. Multiple studies have been published describing new developments and novel strategies utilizing the latest therapeutic and drug delivery technologies to address the efficacy and safety of chemotherapeutics in ovarian cancers. We have identified five novel technologies that are available and, if used, have the potential to mitigate the above-mentioned challenges. Nanocarriers in different forms (Nano-gel, Aptamer, peptide medicated formulations, Antibody-drug conjugation, surface charge, and nanovesicle technologies) are developed and available to be employed to target the cancerous tissue. These strategies are promising to improve clinical efficacy and reduce side effects. We have systematically searched and analyzed published data, as well as the authors intent for the described technology on each publication. We narrowed to 81 key articles and extracted their data to be discussed in this review. In summary, the selected articles investigated the pharmacokinetic properties of drugs combined with nanocarriers and found significant improvement in efficacy and safety by reducing the IC50 values and drug doses. These key papers described promising novel technologies in anti-cancer therapeutic approaches to enable sustained drug release and achieve prolonged drug performance near the tumor site or target tissue.

Progress in novel delivery technologies to improve efficacy of therapeutic antibodies.

Monoclonal antibody-based therapeutics have achieved remarkable success in treating a wide range of human diseases. However, conventional systemic delivery methods have limitations in insufficient target tissue permeability, high costs, repeated administrations, etc. Novel technologies have been developed to address these limitations and further enhance antibody therapy. Local antibody delivery via respiratory tract, gastrointestinal tract, eye and blood-brain barrier have shown promising results in increasing local concentrations and overcoming barriers. Nucleic acid-encoded antibodies expressed from plasmid DNA, viral vectors or mRNA delivery platforms also offer advantages over recombinant proteins such as sustained expression, rapid onset, and lower costs. This review summarizes recent advances in antibody delivery methods and highlights innovative technologies that have potential to expand therapeutic applications of antibodies.

Pharmacological Functions, Synthesis, and Delivery Progress for Collagen as Biodrug and Biomaterial.

Collagen has been widely applied as a functional biomaterial in regulating tissue regeneration and drug delivery by participating in cell proliferation, differentiation, migration, intercellular signal transmission, tissue formation, and blood coagulation. However, traditional extraction of collagen from animals potentially induces immunogenicity and requires complicated material treatment and purification steps. Although semi-synthesis strategies such as utilizing recombinant E. coli or yeast expression systems have been explored as alternative methods, the influence of unwanted by-products, foreign substances, and immature synthetic processes have limited its industrial production and clinical applications. Meanwhile, macromolecule collagen products encounter a bottleneck in delivery and absorption by conventional oral and injection vehicles, which promotes the studies of transdermal and topical delivery strategies and implant methods. This review illustrates the physiological and therapeutic effects, synthesis strategies, and delivery technologies of collagen to provide a reference and outlook for the research and development of collagen as a biodrug and biomaterial.

Current status and prospect for future advancements of long-acting antibody formulations.

INTRODUCTION: Biologics, especially monoclonal antibodies (mAbs), have become a major class of therapeutics in recent years addressing the needs of millions of patients and becoming one of the best-selling treatments in the pharmaceutical market. A wide range of multifaceted chronic diseases have benefitted from antibody therapeutics. Long-term treatment for chronic diseases with mAb therapies can mean a lifetime of frequent injections. Technologies that can minimize the total number of injections present meaningful value to patients and the companies that develop them. AREAS COVERED: This review summarizes the challenges encountered during the development of long-acting versions of mAbs. The focus will be on questions addressed during drug product development, delivery device selection, business implications, and understanding the market potential of long-acting presentations. EXPERT OPINION: Long-acting drug delivery systems have reached the market for small molecules and peptides. However, these drug delivery systems, and their development lessons, cannot be extrapolated directly to antibodies. We must develop new delivery technologies suitable for biologics, identify critical attributes to capture dynamic changes in proteins during the encapsulation process, and develop analytical processes to evaluate long-term stability.

Current Strategy of Monoclonal Antibody: Development, Cloning, Formulation and Drug Delivery.

The development of Monoclonal antibodies (mAbs) has also allowed researchers to understand the complexity of diseases better and find new treatments for difficult-to-treat conditions. Using mAbs, researchers can identify and target specific molecules in the body involved in the disease process. This has allowed for a more targeted treatment approach, which has resulted in improved outcomes for many patients. This hypothesis has been the basis for the development of mAbs that can target an array of illnesses. In the past two decades, therapeutic mAbs have been developed to treat cancer, autoimmune diseases, cardiovascular diseases, and metabolic diseases. For instance, using mAbs has improved outcomes in treating rheumatoid arthritis, multiple sclerosis, and Crohn's disease. However, delivering mAbs in biological systems remains a significant challenge in drug delivery. This is due to their large size, low stability in circulation, and difficulties in achieving their desired action in the target cells. Monoclonal antibodies (mAbs) are an essential tool in biological systems, as they can be used to deliver drugs to specific cell types or tissues. Cloning methods of monoclonal antibody production have been developed to produce mAbs with therapeutic potential. Hence, the present review focused on the development and drug delivery of Monoclonal antibodies (mAbs) in biological systems, which includes cloning methods, various drug delivery technologies, formulation production technology, and its applications in multiple diseases were focused for this review.

Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells.

Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells.

Emerging pharmaceutical therapeutics and delivery technologies for osteoarthritis therapy.

Osteoarthritis (OA) is one of the most common joint degenerative diseases in the world. At present, the management of OA depends on the lifestyle modification and joint replacement surgery, with the lifespan of prosthesis quite limited yet. Effective drug treatment of OA is essential. However, the current drugs, such as the non-steroidal anti-inflammatory drugs and acetaminophen, as well as glucosamine, chondroitin sulfate, hyaluronic acid, are accompanied by obvious side effects, with the therapeutic efficacy to be enhanced. Recently, novel reagents such as IL-1 antagonists and nerve growth factor inhibitors have entered clinical trials. Moreover, increasing evidence demonstrated that active ingredients of natural plants have great potential for treating OA. Meanwhile, the use of novel drug delivery strategies may overcome the shortcomings of conventional preparations and enhance the bioavailability of drugs, as well as decrease the side effects significantly. This review therefore summarizes the pathological mechanisms, management strategies, and research progress in the drug molecules including the newly identified active ingredient derived from medicinal plants for OA therapy, with the drug delivery technologies also summarized, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for OA therapy.

Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.

Delivery of Mesenchymal Stem Cells for Tackling Systemic Disorders.

Development of methods for manipulating and culturing stem cells has enabled the emergence of stem cell therapy as a promising approach in diverse applications, ranging from tissue repair to treatment of intractable diseases such as diabetes, cardiovascular diseases and neurological disorders. Along with technological advances in systemic stem cell delivery, treating multiple injured or pathological sites simultaneously has been made possible. Despite this, most of the works on systemic stem cell transplantation at the moment have focused on the efficiency of tackling local disorders. The prospect of the therapy for enhancing systemic tissue repair, as well as for tackling systemic degenerative disorders, has rarely been seriously considered. The objective of this article is to fill this gap by reviewing the current status of research on systemic stem cell delivery, and by presenting the opportunities and challenges for translating systemic stem cell delivery from the laboratory to the clinic.

Subcutaneous Delivery of High-Dose/Volume Biologics: Current Status and Prospect for Future Advancements.

Subcutaneous (SC) delivery of biologics has traditionally been limited to fluid volumes of 1-2 mL, with recent increases to volumes of about 3 mL. This injection volume limitation poses challenges for high-dose biologics, as these formulations may also require increased solution concentration in many cases, resulting in high viscosities which can affect the stability, manufacturability, and delivery/administration of therapeutic drugs. Currently, there are technologies that can help to overcome these challenges and facilitate the delivery of larger amounts of drug through the SC route. This can be achieved either by enabling biologic molecules to be formulated or delivered as high-concentration injectables (>100 mg/mL for antibodies) or through facilitating the delivery of larger volumes of fluid (>3 mL). The SC Drug Delivery and Development Consortium, which was established in 2018, aims to identify and address critical gaps and issues in the SC delivery of high-dose/volume products to help expand this delivery landscape. Identified as a high priority out of the Consortium's eight problem statements, it highlights the need to shift perceptions of the capabilities of technologies that enable the SC delivery of large-volume (>3 mL) and/or high-dose biologics. The Consortium emphasizes a patient-focused approach towards the adoption of SC delivery of large-volume/high-concentration dosing products to facilitate the continued expansion of the capabilities of novel SC technologies. To raise awareness of the critical issues and gaps in high-dose/volume SC drug development, this review article provides a generalized overview of currently available and emerging technologies and devices that could facilitate SC delivery of high-dose/volume drug formulations. In addition, it discusses the challenges, gaps, and future outlook in high-dose/volume SC delivery as well as potential solutions to exploit the full value of the SC route of administration.

Vaccine innovation prioritisation strategy: Findings from three country-stakeholder consultations on vaccine product innovations.

As part of the Vaccine Innovation Prioritisation Strategy (VIPS), three immunization-stakeholder consultations were conducted between September 2018 and February 2020 to ensure that countries' needs drove the prioritization of vaccine product innovations. All consultations targeted respondents with immunization program experience. They included: (1) an online survey to identify immunization implementation barriers and desired vaccine attributes in three use settings, (2) an online survey to identify and evaluate the most important immunization challenges for ten exemplar vaccines, and (3) in-depth interviews to better understand the perceived programmatic benefits and challenges that could be addressed by nine innovations and to rank the innovations that could best address current challenges. The first consultation included responses from 442 participants in 61 countries, representing 89% of the 496 respondents who correctly completed at least one section of the online survey. For facility-based settings, missed opportunities for vaccination due to reluctance to open multidose vaccine vials was the barrier most frequently selected by respondents. In community-based (outreach) and campaign settings, limited access to immunization services due to geographic barriers was most frequently selected. Multidose presentations with preservative or single-dose presentations were most frequently selected as desired vaccine attributes for facility-based settings while improved thermostability was most frequently selected for outreach and campaign settings. The second online survey was completed by 220 respondents in 54 countries. For the exemplar vaccines, vaccine ineffectiveness or wastage due to heat or freeze exposure and missed opportunities due to multidose vial presentations were identified as the greatest vaccine-specific challenges. In-depth interviews with 84 respondents in six countries ranked microarray patches, dual-chamber delivery devices, and heat-stable/controlled temperature chain qualified liquid vaccines as the three innovations that could have the greatest impact in helping address current immunization program challenges. These findings informed the VIPS prioritization and provided broader application to designing immunization interventions to better meet country needs.

Exploiting the placenta for nanoparticle-mediated drug delivery during pregnancy.

A major challenge to treating diseases during pregnancy is that small molecule therapeutics are transported through the placenta and incur toxicities to the developing fetus. The placenta is responsible for providing nutrients, removing waste, and protecting the fetus from toxic substances. Thus, the placenta acts as a biological barrier between the mother and fetus that can be exploited for drug delivery. Nanoparticle technologies provide the opportunity for safe drug delivery during pregnancy by controlling how therapeutics interact with the placenta. In this Review, we present nanoparticle drug delivery technologies specifically designed to exploit the placenta as a biological barrier to treat maternal, placental, or fetal diseases exclusively, while minimizing off-target toxicities. Further, we discuss opportunities, challenges, and future directions for implementing drug delivery technologies during pregnancy.

Emerging technologies for local cancer treatment.

The fundamental limitations of systemic therapeutic administration have prompted the development of local drug delivery platforms as a solution to increase effectiveness and reduce side effects. By confining therapeutics to the site of disease, local delivery technologies can enhance therapeutic index. This review highlights recent advances and opportunities in local drug delivery strategies for cancer treatment in addition to challenges that need to be addressed to facilitate clinical translation. The benefits of local cancer treatment combined with technological advancements and increased understanding of the tumor microenvironment, present a prime breakthrough opportunity for safer and more effective therapies.

Challenges of vaccine presentation and delivery: How can we design vaccines to have optimal programmatic impact?

Immunization program delivery strategies that enable high vaccine coverage, particularly in inaccessible and remote areas, are critical to achieving optimal vaccine impact. In addition to demonstration of safety and efficacy, there are many factors that influence whether a newly licensed vaccine will be introduced into a country's national immunization program, particularly in resource-constrained environments. This paper describes three case studies of novel approaches that represent the potential for improved programmatic impact by increasing vaccine accessibility in different ways. However, the pathway to regulatory approval, policy recommendation, and program introduction in low- and middle-income countries is complex, requiring engagement with multiple, diverse stakeholders. Consideration of aspects that affect uptake in low- and middle-income countries, during the product development stage, will help better position new or second-generation vaccine products for successful implementation to achieve public health impact.