Asian Journal of Pharmaceutical Sciences最新文献

{"title":"Nanotechnologies meeting natural sources: Engineered lipoproteins for precise brain disease theranostics","authors":"Ruoning Wang ,&nbsp;Xinru Zhang ,&nbsp;Kuanhan Feng ,&nbsp;Wei Zeng ,&nbsp;Jie Wu ,&nbsp;Danni Sun ,&nbsp;Ziyi Lu ,&nbsp;Hao Feng ,&nbsp;Liuqing Di","doi":"10.1016/j.ajps.2023.100857","DOIUrl":"10.1016/j.ajps.2023.100857","url":null,"abstract":"<div><p>Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity, from preventive and diagnostic to therapeutic fields. Lipoproteins, because of their inherent blood-brain barrier permeability and lesion-homing capability, have been identified as promising strategies for high-performance theranostics of brain diseases. However, the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes, which can be critical for individual therapeutics and clinical translation. To address these issues, lipoprotein-inspired nano drug-delivery systems (nano-DDSs), which have been learned from nature, have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions. In this review, the barriers in brain disease treatment, advantages of state-of-the-art lipoprotein-inspired nano-DDSs, and bio-interactions of such nano-DDSs are highlighted. Furthermore, the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized. Specifically, the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed. Finally, the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles, such as exosomes, cell membranes, and bacteria, are discussed.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 5","pages":"Article 100857"},"PeriodicalIF":10.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the development of amorphous solid dispersions: The role of polymeric carriers","authors":"Jie Zhang ,&nbsp;Minshan Guo ,&nbsp;Minqian Luo ,&nbsp;Ting Cai","doi":"10.1016/j.ajps.2023.100834","DOIUrl":"10.1016/j.ajps.2023.100834","url":null,"abstract":"<div><p>Amorphous solid dispersion (ASD) is one of the most effective approaches for delivering poorly soluble drugs. In ASDs, polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level. To prepare the solid dispersions, there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations. Polymer selection is of great importance because it influences the stability, solubility and dissolution rates, manufacturing process, and bioavailability of the ASD. This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers, formulation designs and preparation methods. Furthermore, considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100834"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy","authors":"Yanjing Zhu ,&nbsp;Ruiqi Huang ,&nbsp;Deheng Wang ,&nbsp;Liqun Yu ,&nbsp;Yuchen Liu ,&nbsp;Runzhi Huang ,&nbsp;Shuai Yin ,&nbsp;Xiaolie He ,&nbsp;Bairu Chen ,&nbsp;Zhibo Liu ,&nbsp;Liming Cheng ,&nbsp;Rongrong Zhu","doi":"10.1016/j.ajps.2023.100835","DOIUrl":"10.1016/j.ajps.2023.100835","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. <em>In vivo</em> electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid β (Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aβ phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100835"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/25/main.PMC10460952.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia","authors":"Xiao Liu ,&nbsp;Lili Zhang ,&nbsp;Yueying Yang ,&nbsp;Weiwei Yin ,&nbsp;Yunhu Liu ,&nbsp;Chunyi Luo ,&nbsp;Ruizhe Zhang ,&nbsp;Zhiguo Long ,&nbsp;Yanyan Jiang ,&nbsp;Bing Wang","doi":"10.1016/j.ajps.2023.100826","DOIUrl":"10.1016/j.ajps.2023.100826","url":null,"abstract":"<div><p>Clinically, arsenic trioxide (ATO) was applied to the treatment of acute promyelocytic leukemia (APL) as a reliable and effective frontline drug. However, the administration regimen of As^Ⅲ was limited due to its fast clearance, short therapeutic window and toxicity as well. Based on CD71 overexpressed on APL cells, in present study, a transferrin (Tf)-modified liposome (LP) was established firstly to encapsulate As^Ⅲ in arsenic-nickel complex by nickel acetate gradient method. The As^Ⅲ-loaded liposomes (AsLP) exhibited the feature of acid-sensitive release <em>in vitro</em>. Tf-modified AsLP (Tf-AsLP) were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release As^Ⅲ which stimulated reactive oxygen species level and caspase-3 activity. Tf-AsLP prolonged half-life of As^Ⅲ in blood circulation, lowered systemic toxicity, and promoted apoptosis and induced cell differentiation at lesion site <em>in vivo</em>. Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect, accordingly, a Tf-modified RA liposome (Tf-RALP) was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy. As expected, the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model. Furthermore, APL orthotopic NOD/SCID mice model was established by ⁶⁰CO irradiation and HL-60 cells intravenously injection. The effect of co-administration (Tf-AsLP + Tf-RALP) was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’ apoptosis and differentiation in peripheral blood and bone marrow. Collectively, Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug. Moreover, Tf-AsLP combined with Tf-RALP could achieve better efficacy. Thus, transferrin-modified As^Ⅲ liposome would be a novel clinical strategy to improve patient compliance, with promising translation prospects.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100826"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/5e/main.PMC10423880.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy: Novel insights and perspectives","authors":"Haiying Wang,&nbsp;Chu Qiao,&nbsp;Qiutong Guan,&nbsp;Minjie Wei,&nbsp;Zhenhua Li","doi":"10.1016/j.ajps.2023.100829","DOIUrl":"10.1016/j.ajps.2023.100829","url":null,"abstract":"<div><p>Current antitumor monotherapy has many limitations, highlighting the need for novel synergistic anticancer strategies. Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment. Photodynamic therapy (PDT) causes irreversible chemical damage to target lesions and is widely used in antitumor therapy. However, PDT's effectiveness is usually hindered by several obstacles, such as hypoxia, excess glutathione (GSH), and tumor resistance. Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species (ROS) or reducing GSH levels, and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment (TME). Strategies based on nanoparticles (NPs) can subtly exploit the potential synergy of ferroptosis and PDT. This review explores recent advances and current challenges in the landscape of the underlying mechanisms regulating ferroptosis and PDT, as well as nano delivery system-mediated synergistic anticancer activity. These include polymers, biomimetic materials, metal organic frameworks (MOFs), inorganics, and carrier-free NPs. Finally, we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100829"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/a3/main.PMC10425855.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy","authors":"Yu Tang ,&nbsp;Lanfang Zhang ,&nbsp;Rui Sun ,&nbsp;Baiyi Luo ,&nbsp;Yu Zhou ,&nbsp;Yan Zhang ,&nbsp;Yuqi Liang ,&nbsp;Bo Xiao ,&nbsp;Chenhui Wang","doi":"10.1016/j.ajps.2023.100833","DOIUrl":"10.1016/j.ajps.2023.100833","url":null,"abstract":"<div><p>The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved <em>in vivo</em>. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100833"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/7b/main.PMC10450418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer","authors":"Ying Zhang ,&nbsp;Hao Pan ,&nbsp;Changxiang Yu ,&nbsp;Rui Liu ,&nbsp;Bin Xing ,&nbsp;Bei Jia ,&nbsp;Jiachen He ,&nbsp;Xintao Jia ,&nbsp;Xiaojiao Feng ,&nbsp;Qingqing Zhang ,&nbsp;Wenli Dang ,&nbsp;Zheming Hu ,&nbsp;Xiuping Deng ,&nbsp;Pan Guo ,&nbsp;Zhidong Liu ,&nbsp;Weisan Pan","doi":"10.1016/j.ajps.2023.100827","DOIUrl":"10.1016/j.ajps.2023.100827","url":null,"abstract":"<div><p>Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH₂) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments <em>in vivo</em> and <em>in vitro</em> showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100827"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/eb/main.PMC10425851.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis","authors":"Mahira Zeeshan ,&nbsp;Qurat Ul Ain ,&nbsp;Benno Weigmann ,&nbsp;Darren Story ,&nbsp;Bryan R. Smith ,&nbsp;Hussain Ali","doi":"10.1016/j.ajps.2023.100831","DOIUrl":"10.1016/j.ajps.2023.100831","url":null,"abstract":"<div><p>Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using <em>in vitro, ex vivo</em> techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions’ integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100831"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/ad/main.PMC10425895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis","authors":"Zhimin Li ,&nbsp;Xianjing Feng ,&nbsp;Shixing Luo ,&nbsp;Yanfeng Ding ,&nbsp;Zhi Zhang ,&nbsp;Yifeng Shang ,&nbsp;Doudou Lei ,&nbsp;Jinhong Cai ,&nbsp;Jinmin Zhao ,&nbsp;Li Zheng ,&nbsp;Ming Gao","doi":"10.1016/j.ajps.2023.100830","DOIUrl":"10.1016/j.ajps.2023.100830","url":null,"abstract":"<div><p>Drug delivery via intra-articular (IA) injection has proved to be effective in osteoarthritis (OA) therapy, limited by the drug efficiency and short retention time of the drug delivery systems (DDSs). Herein, a series of modified cross-linked dextran (Sephadex, S0) was fabricated by respectively grafting with linear alkyl chains, branched alkyl chains or aromatic chain, and acted as DDSs after ibuprofen (Ibu) loading for OA therapy. This DDSs expressed sustained drug release, excellent anti-inflammatory and chondroprotective effects both in IL-1<em>β</em> induced chondrocytes and OA joints. Specifically, the introduction of a longer hydrophobic chain, particularly an aromatic chain, distinctly improved the hydrophobicity of S0, increased Ibu loading efficiency, and further led to significantly improving OA therapeutic effects. Therefore, hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100830"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/98/main.PMC10425896.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy","authors":"Xin Liu ,&nbsp;Zhexiang Wang ,&nbsp;Xiaodie Ren,&nbsp;Xinyang Chen,&nbsp;Jinjin Tao,&nbsp;Yuanhui Guan,&nbsp;Xuefeng Yang,&nbsp;Rupei Tang,&nbsp;Guoqing Yan","doi":"10.1016/j.ajps.2023.100832","DOIUrl":"10.1016/j.ajps.2023.100832","url":null,"abstract":"<div><p>Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on <em>in vivo</em> significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.16%), electric neutrality, strong hydrophobicity, and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH. These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 4","pages":"Article 100832"},"PeriodicalIF":10.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/e5/main.PMC10423923.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}