Current Pharmaceutical Design - Online First

Antibiotic resistance poses a significant threat to public health, rendering many life-saving medications ineffective as pathogenic microorganisms develop resistance spontaneously. This results in infections that are difficult to treat, with limited or no treatment options. Traditionally, addressing this challenge involves developing new pharmaceuticals, a lengthy and costly process. However, a more efficient approach lies in improving drug delivery methods, which can be quicker and more economical. In recent years, 3D printing technology has emerged as a groundbreaking, industry-accepted technique that enables the affordable, simple, and rapid manufacturing of pharmaceuticals. This technology supports iterative design-build-test cycles, facilitating the development of a wide range of products, from simple 3D-printed tablets to complex medical devices, tailored for diverse applications. This article explores innovative strategies in the search for novel antibiotics, the development of more effective preventative measures, and, crucially, a deeper understanding of the ecology of antibiotics and antibiotic resistance. It provides an overview of these issues' historical and current status, emphasizing the potential of 3D printing to address antibiotic resistance. Additionally, it discusses how to expand conceptual frameworks in response to recent advancements in chemotherapy, antimicrobials, and antibiotic resistance. The article highlights various notable efforts in utilizing 3D printing to develop antimicrobial dosage forms and medical devices, offering insights into future possibilities.

This review discusses the latest progress in using smart polymeric materials for making medical implants with advanced three-dimensional (3D) and four-dimensional (4D) printing techniques. These smart polymers, also known as stimuli-responsive polymers, can change their properties when exposed to external triggers like temperature, pH, light, or magnetic fields. Integrating these materials with 3D/4D printing allows the creation of highly customizable and functional implants that can adapt to the body's environment. This means implants can now perform additional tasks, such as releasing drugs or changing shape when needed. The review covers different 3D/4D printing methods, the types of smart polymers available, and the benefits of using these materials in medical implants. It also addresses the challenges faced in developing these advanced implants, such as finding suitable materials that are safe for the body and ensuring precise manufacturing. The future prospects of these innovative implants are promising, with potential applications in personalized medicine and non-invasive treatments. This review aims to provide a detailed analysis of recent advancements in stimuli-responsive polymeric materials utilized in additive manufacturing of medical implants. The objective is to explore these materials' clinical implications, address the unique challenges in their development and fabrication, and outline their future potential in enhancing personalized and non-invasive medical treatments.

Cancer is one of the leading causes of death worldwide, which involves the uncontrolled growth of body cells. Cytotoxic chemotherapy drugs, such as tamoxifen, doxorubicin, methotrexate, and cisplatin, have shortcomings that have deprived these treatments of the desired efficiency to destroy tumor cells. Poor pharmacokinetics, severe side effects, and low targeting properties are examples of these shortcomings. Meanwhile, in the last few years, the use of nanocarriers in drug delivery systems has grown significantly. Porphyrins, also called life pigments, are classified as organic complexes. Due to their unique electrochemical and photophysical properties, they have been used in various fields, such as photodynamic therapy, fluorescence, and photoacoustic imaging. However, due to the limitations of these compounds in aqueous environments, such as aggregation by surface molecules, weak absorption in the biological spectral window, self-quenching, and poor chemical and optical stability, there are gaps in the clinical applications of porphyrins. To overcome these challenges, researchers have developed porphyrin-based MOFs. Metal-organic frameworks (MOFs), made of metal ions and clusters coupled with organic linkers, such as porphyrins, through self-assembly, retain the properties of porphyrins while offering additional advantages. Several synthetic approaches and significant advances have been made in the development of porphyrin-based MOFs, including combination therapies, advanced drug delivery, cancer therapy, and photodynamic therapy. Porphyrin-based metal-organic frameworks represent a transformative approach in cancer treatment by integrating multiple therapeutic functions, improving targeting mechanisms, ensuring safety, increasing drug delivery efficiency, and overcoming tumor biological barriers, such as hypoxia, and their day-to-day development promises the formation of more personalized and effective strategies.

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, cardiomyopathy, and early mortality. While advances in multidisciplinary care and pharmacological interventions, including corticosteroids and exon-skipping therapies, have improved patient outcomes, current treatments primarily provide symptomatic relief without addressing the underlying genetic defect. Gene therapy has emerged as a promising approach to modify disease progression, particularly through the use of adeno-associated virus (AAV)-mediated delivery of micro-dystrophin constructs. These truncated genes retain essential functional domains, enabling the restoration of dystrophin expression within the packaging limits of AAV vectors. Early-phase clinical trials have demonstrated encouraging safety profiles and transgene expression; however, challenges such as immune responses, variability in functional improvement, and long-term durability remain. Recent innovations, including optimized AAV capsids, immunomodulatory strategies, and genome editing technologies like CRISPR-Cas9, are actively being explored to overcome these barriers. Additionally, scalable vector manufacturing and the integration of real-world data are essential for broader clinical translation. This review synthesizes current advancements, clinical milestones, and future directions in gene therapy for DMD, emphasizing the need for precise dosing, long-term efficacy, and equitable access to fully realize the therapeutic potential of these evolving strategies.

This review explores the critical role of mitochondria in the immunometabolic processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). It examines the interplay between immune cells, metabolic demands, and tissue environments, emphasizing the impact of bioenergetics on immune responses and disease progression. Mitochondrial dysfunction in chondrocytes and immune cells contributes to OA and RA through mechanisms such as oxidative stress, disrupted calcium homeostasis, and inflammasome activation. In OA, mitochondrial dysfunction in chondrocytes results in impaired energy production, elevated reactive oxygen species (ROS), and calcium imbalance, leading to cartilage degradation and inflammation. The review highlights how disturbances in the mitochondrial respiratory chain and apoptotic pathways drive joint tissue damage. In contrast, RA shows how mitochondrial dysfunction influences chronic inflammation and synovial hyperplasia. The role of mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) is emphasized, illustrating how oxidized mtDNA activates inflammatory pathways, triggers immune responses, and contributes to joint destruction. Additionally, mitochondrial genetic variations may exacerbate inflammation and oxidative stress in RA. The review also discusses the effects of various RA treatments-conventional synthetic anti-rheumatic drugs, biological agents, and targeted synthetic DMARDs-on mitochondrial function. Insights into how these therapies modulate mitochondrial pathways and oxidative stress in immune and joint cells highlight new potential treatment strategies. This review enhances our understanding of OA and RA pathophysiology by elucidating the connections between mitochondria, immune responses, and rheumatic diseases, paving the way for innovative therapies targeting mitochondrial dysfunction.

Small Intestinal Bacterial Overgrowth (SIBO) is a condition marked by an increased proliferation of bacteria in the small intestine. This leads to a range of GI symptoms and nutritional issues. This article examines the preventive and therapeutic roles of nutrition, prebiotics, probiotics, and prokinetics in managing SIBO. Finding the prevalence of SIBO in the general population is challenging due to challenges in diagnosis and different diagnostic methods. Nevertheless, SIBO has been linked to several clinical conditions, such as obesity, celiac disease, irritable bowel syndrome, inflammatory bowel disease, and hepatic cirrhosis. The connection between SIBO and obesity remains controversial and unclear, with contraindicating evidence regarding its prevalence and association with body mass index (BMI). Anatomical changes from surgeries may also contribute to the development of SIBO, and disruptions in the migrating motor complex (MMC) can facilitate intestinal permeability. SIBO can lead to significant malabsorption of nutrients, including carbohydrates, fats, proteins, and iron, resulting in deficiencies and malnourishment. Additionally, increased levels of immunoglobulins observed point toward a possible immune response to bacterial overgrowth. Hence, understanding the prevalence, clinical manifestations, and nutritional impacts of SIBO is crucial for effective prevention and management. This article underscores the potential benefits of nutrition, including prebiotics and probiotics, in modulating gut microbiota and managing SIBO. Furthermore, prokinetics that enhance gastrointestinal motility may offer possible therapeutic advantages in the future. Continued research is necessary to clarify the underlying mechanisms and refine treatment strategies for SIBO.