The emergence of multidrug-resistant (MDR) and extremely drug resistant (XDR) forms of pulmonary tuberculosis (TB) remains a major health challenge in this advanced era of health science. The longer therapy and higher dose of anti-tubercular drugs (ATDs) increases the patient incompliance at its peak levels of intolerance as well as toxicity. In the recent decades, nanoparticulate drug delivery has emerged as an excellent venture for the effective treatment of cancer, infectious diseases, brain as well as TB. Currently, encapsulation and conjugation of therapeutics to polymeric nanoparticles (PNPs) is an attractive strategy to enhance the effectivity of chemotherapeutics and minimize the toxic effects associated with ATDs. Various characteristics of nanoparticles (NPs) such as high stability, high loading efficiency, and high carrying capacity gives preference to the NPs over other drug delivery systems. Multiple or dual drug delivery concept is continuously gaining attention as a strict and favourable requirement of anti-TB therapy. The ideal properties of NPs including controlled or sustained drug release from the matrix enhances drug bioavailability with dose reduction and also enhance compliance of TB patients. Natural and synthetic polymers are playing important role in curtailing the side effects of chemotherapeutics. This review extensively highlights the drug delivery approaches of ATDs and emphasized on the importance and application of PNPs to combat TB.
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http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2022039981 | DOI Listing |
Nanotechnology
January 2025
Department of Biotechnology, Kalasalingam Academy of Research and Education (Deemed to be University), Anand Nagar, School of Bio, Chemical & Process Enginneering, Krishnankoil, Krishnan Kovil, Tamil Nadu, 626126, INDIA.
Significant progress has been made in cancer therapy with protein-based nanocarriers targeted directly to surface receptors for drug delivery. The nanocarriers are a potentially effective solution for the potential drawbacks of traditional chemotherapy, such as lack of specificity, side effects, and development resistance. Peptides as nanocarriers have been designed based on their biocompatible, biodegradable, and versatile functions to deliver therapeutic agents into cancer cells, reduce systemic toxicity, and maximize therapy efficacy through utilizing targeted ligands such as antibodies, amino acids, vitamins, and other small molecules onto protein-based nanocarriers and thus ensuring that drugs selectively accumulate in the cancer cells instead of healthy organs/drug release at a target site without effects on normal cells, which inherently caused less systemic toxicity/off-target effect.
View Article and Find Full Text PDFACS Nano
January 2025
Wuya Faculty of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Antidrug antibodies (ADAs) against biologics present a major challenge for sustained biotherapy, including enzyme replacement therapies and adeno-associated virus (AAV) gene therapies. These antibodies arise from undesirable immune responses, leading to altered pharmacokinetics, reduced efficacy, and adverse reactions. In this study, we introduced a rationally designed lipid-rapamycin (Rapa)-based nanovaccine to restore immune tolerance to biologics and overcome drug resistance.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Combination therapies using checkpoint inhibitors with immunostimulatory agonists have attracted great attention due to their synergistic therapeutic effects for cancer treatment. However, such combination immunotherapies require specific timing of doses to show sufficient antitumor efficacy. Sequential treatment usually requires multiple administrations of the individual drugs at specific time points, thus increasing the complexity of the drug regimen and compromising patient compliance.
View Article and Find Full Text PDFJ Med Chem
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Natural products (NPs) continue to serve as an invaluable source in drug discovery, and peripheral evolution of NPs is a highly efficient evolution strategy. Herein, we describe a unified "methyl to amide" peripheral evolution of Tanshinone IIA and Cryptotanshinone for discovery of NLRP3 inflammasome inhibitors. There were 54 compounds designed and prepared, while the chemoinformatic analysis revealed that these evolved NP analogues occupy a unique chemical space.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Automation, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
Studying the changes in cellular transcriptional profiles induced by small molecules can significantly advance our understanding of cellular state alterations and response mechanisms under chemical perturbations, which plays a crucial role in drug discovery and screening processes. Considering that experimental measurements need substantial time and cost, we developed a deep learning-based method called Molecule-induced Transcriptional Change Predictor (MiTCP) to predict changes in transcriptional profiles (CTPs) of 978 landmark genes induced by molecules. MiTCP utilizes graph neural network-based approaches to simultaneously model molecular structure representation and gene co-expression relationships, and integrates them for CTP prediction.
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