Critical Reviews in Therapeutic Drug Carrier Systems最新文献

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized with symmetrical progression of joint deformity that is often diagnosed at a chronic condition with other associated pathological conditions such as pericarditis, keratitis, pulmonary granuloma. Despite the understanding of RA pathophysiology in disease progression, current clinical treatment options such as disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) provide only palliative therapy while causing adverse side effects such as off-target multi-organ toxicity and risk of infections. Further, available drug delivery strategies to treat RA pathogenicity does not successfully reach the site of action due to various barriers such as phagocytosis and first pass effect in addition to the disease complexity and unknown etiology, thereby leading to the development of irreversible joint dysfunction. Therefore, novel and effective strategies remain an unmet need to control the disease progression and to maintain the balance between pro- and anti-inflammatory cytokines. This review provides a comprehensive outlook on the RA pathophysiology and its corresponding disease progression. Contributions of synoviocytes such as macrophages, fibroblast-like cells in increasing invasiveness to exacerbate joint damage is also outlined in this review, which could be a potential future therapeutic target to complement the existing treatment regimens in controlling RA pathogenesis. Further, various smart drug delivery approaches under research to achieve maximum therapeutic efficacy with minimal adverse side effects have been discussed, which in turn emphasize the unmet challenges and future perspectives in addressing RA complications.

Brain tumor is one of the reasons for several mortality cases in hospitals. Early detection and diagnosis of brain tumors are necessary to cure the disease early. The extraction of the tumor from the brain's magnetic resonance image (MRI) is considered to be a difficult task when done by clinical experts, and it is also pretty time-consuming. These drawbacks can be overcome by using computer vision-based technologies. The proposed method detects brain tumor crossing the blood-brain barrier (BBB) through MRI images by using Berkeley wavelet transformation (BWT) for segmenting the affected areas. Support vector machine (SVM) is used for classification purpose by which the classification process is divided into two different categories namely, the tumor affected and tumor non-affected parts. Initially, the acquired image is converted to a greyscale from RGB. Then, image segmentation is done. During the image segmentation, morphological operations are carried out. Two morphological operations have been used in the proposed system. They are erosion and dilation. Both these techniques are used for edge detection. In erosion, the pixels are removed from the edges of the tumor image. In dilation, pixels are added at the edges of the tumor images. After the morphological operation, feature extraction is carried out. The features like homogeneity, contrast of the image and the energy might be determined. Then, the image is classified using the SVM classification algorithm. The experimental results have been tabulated and depicted using graphical representations. Comparing to the existing approaches the proposed method is proved to be better in accuracy and efficiency.

Cancer stem cells (CSCs) are a category of cancer cells endowed with the ability to renew themselves, undergo unregulated growth, and exhibit a differentiation capacity akin to that of normal stem cells. CSCs have been linked with tumor metastasis and cancer recurrence due to their ability to elude immune monitoring. As a result, targeting CSCs specifically may improve the efficacy of cancer therapy. Recently, the use of nanotechnology has gained substantial attention in cancer treatment. Cancer nanotechnology is an interdisciplinary field of research where nano-biotechnology fosters the combination of diagnostics and treatments, which is an important part of a personalized approach to cancer treatment. Thus, using nanoparticles against cancer cells and CSCs simultaneously may lead to the development of a better therapeutic intervention to eradicate cancer. In this review, we describe recent achievements in cancer therapy targeting CSCs of various malignancies, such as lung cancer, breast cancer, colorectal cancer, and prostate cancer, by using nanotechnology.

Brain cancer continues to be one of the most formidable malignancies to manage, mainly attributable to the presence of the blood-brain barrier (BBB) limiting the permeability of drugs and the diverse characteristics of brain tumors complicating treatment. The management of brain tumors has been hampered by many different factors, including the impermeability of the BBB, which restricts the delivery of chemotherapeutic agents to the tumor site, as well as intertumoral heterogeneity and the influence of brain tumor stem cells. In addition, small molecular weight drugs cannot specifically accumulate in malignant cells and have a limited circulation half-life. Nanoparticles (NPs) can be engineered to traverse the BBB and transport therapeutic medications directly into the brain, enhancing their efficacy compared with the conventional delivery of unbound drugs. Surface modifications of NPs can boost their efficiency by increasing their selectivity towards tumor receptors. This review covers treatment methods for malignant gliomas, associated risk factors, and improvements in brain drug administration, emphasizing the future potential of polymeric NPs and their mechanism for crossing the BBB. To surmount these obstacles, the newly formulated drug-delivery approach utilizing NPs, particularly those coated with cell membranes, has demonstrated potential in treating brain cancer. These NPs provide targeted tumor specificity, biocompatibility, extended circulation, enhanced BBB penetration, and immune evasion. This review focuses on coating strategies for PLGA NPs, particularly dual-targeting methods, to enhance BBB permeability and tumor-targeted delivery of drugs in brain cancer.

The emergence of messenger ribonucleic acid (mRNA) vaccines as an alternative platform to traditional vaccines has been accompanied by advances in nanobiotechnology, which have improved the stability and delivery of these vaccines through novel nanoparticles (NPs). Specifically, the development of NPs for mRNA delivery has facilitated the loading, protection and release of mRNA in the biological microenvironment, leading to the stimulation of mRNA translation for effective intervention strategies. Intriguingly, two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have been permitted for emergency usage authorization to prevent COVID-19 infection by USFDA. Both mRNA vaccines utilized lipidic NPs (LNPs) as a delivery platform and demonstrated superior efficacy and safety profiles compared to traditional vaccines. This review article gives insight into ongoing pre-clinical and clinical developments of mRNA vaccine candidates, their efficacy against coronavirus variants, and analysis of NP-based approaches to recognize their potential for forthcoming growth. This review article highlights recent advances in delivery strategies, including LNPs, polymeric NPs, and exosomes, for effective immunization against COVID-19. The key challenges associated with mRNA NPs have been identified, and potential strategies to overcome these difficulties have been proposed. Production of nanomaterials for specific mRNA applications can offer new insights into next-generation nanomaterials, revolutionizing mRNA technology.

Microneedle-based delivery systems have emerged as a groundbreaking technology in the realm of targeted cancer therapy. By facilitating the transdermal administration of therapeutic agents, microneedles offer a minimally invasive method to overcome the limitations posed by conventional drug delivery systems. This review comprehensively examines the potential of microneedles to enhance drug bioavailability, improve therapeutic outcomes, and reduce systemic toxicity. We explore the diverse applications of MNs in cancer treatment, including their use in chemotherapy, where MNs enable direct delivery of chemotherapeutic agents to tumor sites, thus maximizing drug efficacy and minimizing adverse effects. Additionally, we discuss the role of MNs in immunotherapy, highlighting how they can be used to deliver immune-modulating agents that activate localized immune responses against cancer cells. Furthermore, the potential of microneedles in gene therapy is addressed, emphasizing their ability to deliver genetic material directly to tumor cells, thereby offering a novel approach to cancer treatment. The review also delves into the challenges associated with MN-based therapies, such as ensuring consistent and controlled drug delivery, addressing patient variability, and overcoming manufacturing and scalability issues. Despite these challenges, the advancements in microneedle technology and the promising results from preclinical and clinical studies underscore their transformative potential in cancer therapy. We emphasize the need for further research and clinical trials to validate the efficacy and safety of microneedles.

Treating neurological disorders is challenging due to the blood-brain barrier (BBB), which limits therapeutic agents, including proteins and peptides, from entering the central nervous system. Despite their potential, the BBB's selective permeability is a significant obstacle. This review explores recent advancements in protein therapeutics for BBB-targeted delivery and highlights computational tools. Strategies such as nanoparticulate-mediated delivery, nose-to-brain delivery, lipid-based approaches, exosomes, cell-penetrating peptides (CPPs), and BBB shuttle peptides have been developed to overcome this barrier. Nanoparticulate systems deliver protein therapeutics across the BBB and can be surface-functionalized to target therapeutic agents into the brain parenchyma. Nose-to-brain delivery is a minimally invasive approach to bypass the BBB. Lipid-based strategies like liposomal systems and nanostructured lipid carriers enhance protein therapies by overcoming BBB restrictions. Exosomes, with unique lipid and surface protein compositions, and CPPs provide versatile drug delivery across the BBB. BBB shuttle peptides, designed for targeted brain delivery, show enhanced stability, efficiency, and cargo transport. Computational tools, notably molecular dynamics simulations, are essential in optimizing protein therapeutics for BBB penetration. These tools offer insights into molecular interactions, guiding the design and optimization of protein therapeutics for better brain penetration. Despite accuracy, limitations due to the BBB's complexity, integrating realistic models and experimental data can improve predictions.

Over the past few years, delivery tactics for enhancing drug bioavailability, biocompatibility, and therapeutic index have advanced significantly in innovative strategies, encompassing delivery of small molecules, proteins and peptides, nucleic acids, and, most recently, live-cell therapies. Challenges associated with different drug delivery systems such as reducing off-target toxicity, improving solubility and permeability, non-invasive handling, overcoming biological obstacles, decreasing immunogenicity, improving stability, getting into the nucleus or cytoplasm, viability and persistence in vivo, etc. can be overcome by any one of the three strategies- Modification of drug molecule, change in physiological environment, and using novel drug carrier. This article describes the problems with traditional medication delivery methods and how other methods have been developed to overcome those problems. Additionally, this review also provides knowledge on a few unique technique of drug delivery including nanotechnology, 3D printing, AI aided delivery of therapeutics, etc.

Cervical cancer is the fourth most common cause of morbidity and mortality in women. The major causative factor for cervical cancer is primary prolonged infection with human papillomavirus, along with secondary factors such as immunodeficiency, smoking, low socioeconomic standards, poor hygiene, and overuse of oral contraceptives. A grave need exists to practice novel strategies to overcome existing drawbacks of conventional therapy such as chemotherapy, radiation therapy, and surgery. Cancer immunotherapy works by strengthening the immune system of the host to combat against the cancerous cells. Immunotherapy in cervical cancer treatment has demonstrated long-lasting effects; however, the response to such therapies was nominal due to its prominent limitations such as immunosuppressive behavior of the tumor. Presently plethora of nanoplatforms such as polymeric nanoparticles, micelles, liposomes, and dendrimers are being maneuvered with cancer immunotherapy. The amalgamation of nanotechnology and immunotherapy in the treatment of cervical cancer is conceivable due to the mutual association between the tumor microenvironment and immunosurveillance. Safety concerns of nanoplatforms with immunotherapeutics such as toxicity, inflammation, and unwanted accumulation in tissues could be surmounted by surface modification methods. This review highlights the benefits of the amalgamation of nanotechnology and immunotherapy to improve shortcomings applicable to the conventional delivery of cancer treatment. We also aim to outline the nanoimmunotherapy sophistications and future translational avenues in this rapidly flourishing cancer treatment modality.

Onychomycosis, a nail infection prevalent in 50 to 60% of all nail illnesses globally, caused by dermatophytes, poses significant challenges to current therapies due to their limitations in effective administration. This review explores recent advancements in novel drug delivery systems while exploring the molecular mechanisms underlying onychomycosis progression. The physicochemical properties of antifungal treatments and the intricate structure of the nail plate present challenges and can be addressed by nanotechnology-enabled solutions. Furthermore, the review extensively covers diagnostic methods crucial for accurate onychomycosis identification. This review offers insights to enhance onychomycosis management by elucidating mechanistic aspects of the disease. Emphasizing the role of nanotechnology in drug delivery systems, it addresses current treatment challenges using innovative approaches. Moreover, the evaluation of various formulations highlights opportunities to improve therapeutic efficacy. Overall, this comprehensive review explores the current status, challenges, diagnostics advances, and novel approaches for the administration of drugs for the management of onychomycosis.