{"title":"Engineered Exosomes for Drug Delivery in Cancer Therapy: A Promising Approach and Application.","authors":"Peiwen Fu, Siqi Yin, Huiying Cheng, Wenrong Xu, Jiajia Jiang","doi":"10.2174/1567201820666230712103942","DOIUrl":"10.2174/1567201820666230712103942","url":null,"abstract":"<p><p>A significant amount of research effort is currently focused on investigating the role of exosomes in various cancers. These tiny vesicles, apart from acting as biomarkers, also play a crucial role in tumor formation and development. Several studies have demonstrated that exosomes can be a drug delivery vehicle for cancer therapy. In this paper, we highlight the key advantages of exosomes as a drug delivery candidate, with a particular focus on their low immunogenicity, natural targeting ability and suitable mechanical properties. Furthermore, we propose that the selection of appropriate exosomes and drug loading methods based on therapeutic goals and product heterogeneity is essential for preparing engineered exosomes. We comprehensively analyzed the superiorities of current drug-loading methods to improve the creation of designed exosomes. Moreover, we systematically review the applications of engineered exosomes in various therapies such as immunotherapy, gene therapy, protein therapy, chemotherapy, indicating that engineered exosomes have the potential to be reliable and, safe drug carriers that can address the unmet needs in cancer clinical practice.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"817-827"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rajat Patel, Utkarsha Kuwar, Nidhi Dhote, Amit Alexander, Kartik Nakhate, Parag Jain, Ajazuddin
{"title":"Natural Polymers as a Carrier for the Effective Delivery of Antineoplastic Drugs.","authors":"Rajat Patel, Utkarsha Kuwar, Nidhi Dhote, Amit Alexander, Kartik Nakhate, Parag Jain, Ajazuddin","doi":"10.2174/1567201820666230112170035","DOIUrl":"10.2174/1567201820666230112170035","url":null,"abstract":"<p><p>Cancer is a broad term for a set of disorders marked by the development of physically and functionally changed cells that proliferate uncontrollably, infect neighboring tissues, and result in malignant tumours, 'neoplasm'. Cancer remains a difficult disease to treat because of the significant adverse effects and poor pharmacokinetic profile of antineoplastic drugs, despite advancements in our understanding of the features and behavior of tumor cells in recent decades. In this series, the role of natural polymers is prominent as a component of a novel delivery system of anticancer drugs. These natural polymeric drug delivery systems (NPDDS) have many advantages over synthetic polymers like controlled delivery, biodegradability, inexpensive, low toxicity profile, and easily obtainable. These polymers further modify for the targeting of tumour cells. This review discusses and critically analyses the different natural polymers, such as chitosan, cellulose, starch, albumin, dextran, fucoidan, gelatin, etc., in terms of natural ingredient-based polymeric nanocarriers specifically for cancer therapy. It also describes benefits, drawbacks, and opinions and provides insights about the efficacy of NPDDS as well as its future perspectives and tabulated recent patents and cases under clinical trials exploited for cancer treatment.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"193-210"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wesam W Mustafa, Mouhamad Khoder, Hamdy Abdelkader, Richard Singer, Raid G Alany
{"title":"Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement.","authors":"Wesam W Mustafa, Mouhamad Khoder, Hamdy Abdelkader, Richard Singer, Raid G Alany","doi":"10.2174/1567201820666230320164210","DOIUrl":"10.2174/1567201820666230320164210","url":null,"abstract":"<p><strong>Background: </strong>Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400- 600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs).</p><p><strong>Methods: </strong>Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via</i> DSC, XRD, FTIR, SEM, dissolution, and docking.</p><p><strong>Results: </strong>The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ -CD > HPβ-CD > β-CD. FD method was superior to both CO and PM.</p><p><strong>Conclusion: </strong>Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"126-139"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan Jiang, Yi Yuan, Feng Peng, Yi Deng, Chao Ren, Chongzhi Liu, Hai Dong, Tao Tu
{"title":"Erythrocyte-based Drug Delivery: How Far from Clinical Application?","authors":"Yuan Jiang, Yi Yuan, Feng Peng, Yi Deng, Chao Ren, Chongzhi Liu, Hai Dong, Tao Tu","doi":"10.2174/1567201820666230320103529","DOIUrl":"10.2174/1567201820666230320103529","url":null,"abstract":"<p><p>Erythrocytes are responsible for delivering oxygen throughout the body. They have become suitable drug carriers due to outstanding advantages, such as a long lifespan in circulation, high biosafety, and low immunogenicity. Although erythrocyte-based drug delivery has good application prospects and has become a research hotspot in related fields, the application of erythrocyte-based drug delivery systems is rare in the clinic now. In this review, we discuss the characteristics of erythrocytes, diverse drug-loading approaches, and research progress of erythrocyte-based drug delivery systems. Finally, we explore the challenges of erythrocyte-based drug delivery in clinical application.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"52-64"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lily Ellysa Hashim, Akmal Hidayat Sabri, Malihah Athirah Mohamad, Qonita Kurnia Anjani, Mohd Faiz Mustaffa, Khuriah Abdul Hamid
{"title":"Circumventing the Gastrointestinal Barrier for Oral Delivery of Therapeutic Proteins and Peptides (PPTS): Current Trends and Future Trajectories.","authors":"Lily Ellysa Hashim, Akmal Hidayat Sabri, Malihah Athirah Mohamad, Qonita Kurnia Anjani, Mohd Faiz Mustaffa, Khuriah Abdul Hamid","doi":"10.2174/1567201820666230418091506","DOIUrl":"10.2174/1567201820666230418091506","url":null,"abstract":"<p><p>Therapeutic proteins and peptides (PPTs) have become one of the most important biological molecules for the management of many common and complex diseases due to their high specificity and high bioactivity. However, these biomolecules are mainly given by the hypodermic injection, which often leads to poor patient compliance due to the invasive nature of this route of administration. The oral route has been considered the most convenient and patient-friendly route for drug delivery relative to hypodermic injections. Despite the ease and simplicity conferred by oral administration, this drug delivery route suffers rapid peptide degradation in gastric fluid and low intestinal uptake. In order to circumvent these issues, several strategies, such as enzyme inhibitors, permeation enhancers, chemical modification, mucoadhesive and stimuli-responsive polymers, and specialised particulate formulation have been developed. Such strategies are designed with the aim of protecting PPTs from the harsh gastrointestinal environment as well as providing a strategy to enhance the uptake of the therapeutic across the gastrointestinal tract. This review aims to provide an overview of the current development in enteral drug delivery strategies for PPTs. The design of these drug delivery systems in overcoming physical and chemical barriers along the gastrointestinal tract while improving oral bioavailability will be highlighted and discussed.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"211-235"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hong Shu, Wenhao Lv, Zhi-Jian Ren, Hui Li, Tiantian Dong, Yao Zhang, Fang Nie
{"title":"Ultrasound-mediated PLGA-PEI Nanobubbles Carrying STAT6 SiRNA Enhances NSCLC Treatment <i>via</i> Repolarizing Tumor-associated Macrophages from M2 to M1 Phenotypes.","authors":"Hong Shu, Wenhao Lv, Zhi-Jian Ren, Hui Li, Tiantian Dong, Yao Zhang, Fang Nie","doi":"10.2174/1567201820666230724151545","DOIUrl":"10.2174/1567201820666230724151545","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages (TAMs) are crucial for non-small cell lung cancer (NSCLC) development.</p><p><strong>Objective: </strong>In this study, polylactic acid-co-glycolic acid (PLGA)-polyethylenimine (PEI) nanobubbles (NBs) carrying STAT6 siRNA were prepared and combined with ultrasound-mediated nanobubbles destruction (UMND) to silence the STAT6 gene, ultimately repolarizing TAMs from the M2 to the M1 phenotype, treating NSCLC <i>in vitro</i>.</p><p><strong>Methods: </strong>PLGA-PEI NBs-siRNA were prepared and characterised, and their respective ultrasound imaging, biological stabilities and cytotoxicities were detected. Transfection efficiency was evaluated by fluorescence microscopy and flow cytometry. Repolarization of THP-1-derived M2-like macrophages was determined by qPCR and flow cytometry. NSCLC cells (A549) were co-cultured with transfected M2-like macrophages or their associated conditioned medium (CM). Western blotting was used to detect STAT6 gene silencing in M2-like macrophages and markers of epithelial and mesenchymal in A549 cells. The proliferation of A549 cells was detected using CCK-8 and cell colony formation assays. Transwell assays were used to detect the migration and invasion of A549 cells.</p><p><strong>Results: </strong>PLGA-PEI NBs-siRNA had an average size of 223.13 ± 0.92 nm and a zeta potential of about -5.59 ± 0.97 mV. PLGA-PEI NBs showed excellent ultrasonic imaging capability in addition to biological stability to protect siRNA from degradation. UMND enhanced PLGA-PEI NBs-STAT6 siRNA transfection in M2-like macrophages, which made M2-like macrophages repolarize to M1-like macrophages and prevented proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in A549 cells.</p><p><strong>Conclusion: </strong>UMND enhanced PLGA-PEI NBs-STAT6 siRNA to repolarize TAMs from the M2 to the M1 phenotype, thus treating NSCLC. These findings provide a promising therapeutic approach for enhancing NSCLC immunotherapy.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"1114-1127"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Solubility Enhancement and Antioxidation Maintenance of CBD Encapsulated in the P407-RUB Nano-micelle System.","authors":"Yan-Ting Su, Jian Zhang","doi":"10.2174/1567201820666230330090025","DOIUrl":"10.2174/1567201820666230330090025","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study is to improve the water solubility and stability of cannabidiol (CBD) utilizing micelle technology.</p><p><strong>Materials and methods: </strong>Mixing of rubusoside (RUB) with Poloxamer 407 (P407) was explored as the wall material for the preparation of CBD micelles. In this study, CBD-loaded mixed micelles (CBD-M) composed of P407 and RUB was successfully formed by self-assembly then solid were prepared by solvent evaporation. The saturated solubility of CBD-loaded micelles in water increased to 15.60 mg/mL, 1560-fold compared with its intrinsic solubility (0.01 mg/mL). The average size of CBD-M was 103 ± 2.66 nm and the encapsulation efficiency for CBD was 92.8 + 4.7 %, and 18.6 + 0.94% for drug-loading.</p><p><strong>Results: </strong>The morphology and encapsulation of CBD-M were characterized by TEM, FI-IR, DSC and TG. The CBD-M solution was stable and CBD-M did not precipitate or leak after being diluted and centrifugated. Besides, CBD-M solution was stable for 6 months at 4°C and room temperature. In vitro antioxidant studies found that the antioxidant activity of CBD remained at the same level after micellization.</p><p><strong>Conclusion: </strong>These results suggest that CBD-M may be a promising and competitive formulation for the delivery of CBD, laying a foundation for improving the bioavailability in the future.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"271-282"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9590298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Artificial Intelligence in Drug Discovery and Target Identification in Cancer.","authors":"Vishal Sharma, Amit Singh, Sanjana Chauhan, Pramod Kumar Sharma, Shubham Chaudhary, Astha Sharma, Omji Porwal, Neeraj Kumar Fuloria","doi":"10.2174/1567201821666230905090621","DOIUrl":"10.2174/1567201821666230905090621","url":null,"abstract":"<p><p>Drug discovery and development (DDD) is a highly complex process that necessitates precise monitoring and extensive data analysis at each stage. Furthermore, the DDD process is both timeconsuming and costly. To tackle these concerns, artificial intelligence (AI) technology can be used, which facilitates rapid and precise analysis of extensive datasets within a limited timeframe. The pathophysiology of cancer disease is complicated and requires extensive research for novel drug discovery and development. The first stage in the process of drug discovery and development involves identifying targets. Cell structure and molecular functioning are complex due to the vast number of molecules that function constantly, performing various roles. Furthermore, scientists are continually discovering novel cellular mechanisms and molecules, expanding the range of potential targets. Accurately identifying the correct target is a crucial step in the preparation of a treatment strategy. Various forms of AI, such as machine learning, neural-based learning, deep learning, and network-based learning, are currently being utilised in applications, online services, and databases. These technologies facilitate the identification and validation of targets, ultimately contributing to the success of projects. This review focuses on the different types and subcategories of AI databases utilised in the field of drug discovery and target identification for cancer.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"870-886"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Age-Related Macular Degeneration - Therapies and Their Delivery.","authors":"Chandrasekar Ponnusamy, Puratchikody Ayarivan, Preethi Selvamuthu, Subramanian Natesan","doi":"10.2174/1567201820666230510100742","DOIUrl":"10.2174/1567201820666230510100742","url":null,"abstract":"<p><p>Age-related macular degeneration (ARMD) is a degenerative ocular disease that is the most important cause of irreversible vision loss in old-aged people in developed countries. Around fifty percent of vision impairments in developed countries are due to ARMD. It is a multifaceted disease that is associated with both genetic and environmental risk factors. The most important treatments option for ARMD includes laser photocoagulation, photodynamic therapy (PDT), Anti-VEGF Injections, and combination therapies. In this review, we also propose that topical ocular drug delivery with nanocarriers has more attention for the treatment of ARMD. The nanocarriers were specially designed for enhanced corneal residential time, prolonged drug release and action, and minimizing the frequency of administrations. Different types of nanocarriers were developed for the topical ocular delivery system, such as nanomicelles, nanoemulsions, nanosuspensions, liposomes, and polymeric nanoparticles. These topical ocular nanocarriers were administered topically, and they can fix the hydrophobic substances, increase solubility and improve the bioavailability of an administered drug. Hence the topical ocular delivery systems with nanocarriers provide a safe and effective therapeutic strategy and promising tool for the treatment of posterior segment ocular diseases ARMD.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"683-696"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monoclonal Antibodies and Antibody-drug Conjugates as Emerging Therapeutics for Breast Cancer Treatment.","authors":"Swati Saini, Nisha Gulati, Rajendra Awasthi, Vimal Arora, Sachin Kumar Singh, Shobhit Kumar, Gaurav Gupta, Kamal Dua, Rakesh Pahwa, Harish Dureja","doi":"10.2174/1567201820666230731094258","DOIUrl":"10.2174/1567201820666230731094258","url":null,"abstract":"<p><p>When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multi-specific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"993-1009"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9898276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}