Drug Delivery最新文献

{"title":"Legumain/pH dual-responsive lytic peptide-paclitaxel conjugate for synergistic cancer therapy.","authors":"Shanshan Zheng,&nbsp;Yue Cai,&nbsp;Yulu Hong,&nbsp;Yubei Gong,&nbsp;Licheng Gao,&nbsp;Qingyong Li,&nbsp;Le Li,&nbsp;Xuanrong Sun","doi":"10.1080/10717544.2022.2081380","DOIUrl":"https://doi.org/10.1080/10717544.2022.2081380","url":null,"abstract":"<p><p>After molecule targeted drug, monoclonal antibody and antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs) have become the next generation targeted anti-tumor drugs due to its properties of low molecule weight, efficient cell penetration, low immunogenicity, good pharmacokinetic and large-scale synthesis by solid phase synthesis. Herein, we present a lytic peptide PTP7-drug paclitaxel conjugate assembling nanoparticles (named PPP) that can sequentially respond to dual stimuli in the tumor microenvironment, which was designed for passive tumor-targeted delivery and on-demand release of a tumor lytic peptide (PTP-7) as well as a chemotherapeutic agent of paclitaxel (PTX). To achieve this, tumor lytic peptide PTP-7 was connected with polyethylene glycol by a peptide substrate of legumain to serve as hydrophobic segments of nanoparticles to protect the peptide from enzymatic degradation. After that, PTX was connected to the amino group of the polypeptide side chain through an acid-responsive chemical bond (2-propionic-3-methylmaleic anhydride, CDM). Therefore, the nanoparticle (PPP) collapsed when it encountered the weakly acidic tumor microenvironment where PTX molecules fell off, and further triggered the cleavage of the peptide substrate by legumain that is highly expressed in tumor stroma and tumor cell surface. Moreover, PPP presents improved stability, improved drug solubility, prolonged blood circulation and significant inhibition ability on tumor growth, which gives a reasonable strategy to accurately deliver small molecule drugs and active peptides simultaneously to tumor sites.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1764-1775"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10760669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer.","authors":"Yao Xiao,&nbsp;Wenxia Yao,&nbsp;Mingzhen Lin,&nbsp;Wei Huang,&nbsp;Ben Li,&nbsp;Bin Peng,&nbsp;Qinhai Ma,&nbsp;Xinke Zhou,&nbsp;Min Liang","doi":"10.1080/10717544.2022.2079769","DOIUrl":"https://doi.org/10.1080/10717544.2022.2079769","url":null,"abstract":"<p><p>This study aimed to explore the anti-tumor effect of icaritin loading poly (lactic-co-glycolic acid) nanoparticles (refer to PLGA@Icaritin NPs) on gastric cancer (GC) cells. Transmission Electron Microscope (TEM), size distribution, zeta potential, drug-loading capability, and other physicochemical characteristics of PLGA@Icaritin NPs were carried out. Furthermore, flow cytometry, confocal laser scanning microscope (CLSM), Cell Counting Kit-8 (CCK-8), Transwell, Elisa assay and Balb/c mice were applied to explore the cellular uptake, anti-proliferation, anti-metastasis, immune response activation effects, and related anti-tumor mechanism of PLGA@Icaritin NPs <i>in vitro</i> and <i>in vivo</i>. PLGA@Icaritin NPs showed spherical shape, with appropriate particle sizes and well drug loading and releasing capacities. Flow cytometry and CLSM results indicated that PLGA@Icaritin could efficiently enter into GC cells. CCK-8 proved that PLGA@Icaritin NPs dramatically suppressed cell growth, induced Lactic dehydrogenase (LDH) leakage, arrested more GC cells at G2 phase, and inhibited the invasion and metastasis of GC cells, compared to free icaritin. In addition, PLGA@Icaritin could help generate dozens of reactive oxygen species (ROS) within GC cells, following by significant mitochondrial membrane potentials (MMPs) loss and excessive production of oxidative-mitochondrial DNA (Ox-mitoDNA). Since that, Ox-mitoDNA further activated the releasing of damage associated molecular pattern molecules (DAMPs), and finally led to immunogenic cell death (ICD). Our <i>in vivo</i> data also elaborated that PLGA@Icaritin exerted a powerful inhibitory effect (∼80%), compared to free icaritin (∼60%). Most importantly, our results demonstrated that PLGA@Icaritin could activate the anti-tumor immunity via recruitment of infiltrating CD4+ cells, CD8+ T cells and increased secretion of cytokine immune factors, including interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1).⁺⁺ Our findings validate that the successful design of PLGA@Icaritin, which can effectively active ICD and facilitate tumor recruitment in GC through inducing mitoDNA oxidative damage.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1712-1725"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting curcumin activity against human prostatic cancer PC3 cells by utilizing scorpion venom conjugated phytosomes as promising functionalized nanovesicles.","authors":"Mohammed W Al-Rabia, Nabil A Alhakamy, Waleed Y Rizg, Adel F Alghaith, Osama A A Ahmed, Usama A Fahmy","doi":"10.1080/10717544.2022.2048133","DOIUrl":"10.1080/10717544.2022.2048133","url":null,"abstract":"<p><p>Prostate cancer (PC) is emerging as one of the leading causes of mortality and morbidity worldwide. Curcumin (CUR) is a well-known phytochemical, and scorpion venom (SV) is a natural peptide with proven anticancer properties. However, these natural bioactive agents are limited by low solubility, low bioavailability, poor thermal stability, and short half-lives. Therefore, the aim of this study was to fabricate SV-conjugated CUR phytosomes as promising functionalized nanovesicles and assess their anticancer efficacy in human prostatic cancer PC3 cells. CUR-Phytosome-SV was fabricated using experimental design software in which the zeta potential and particle sizes were used as dependent variables. The anticancer effect of the fabricated formulation was determined by performing a tetrazolium (MTT) assay, cell cycle analysis, annexin V staining, and examining the expression levels of Bcl-associated X-protein (Bax), p53, caspase-3, B-cell lymphoma 2 (Bcl-2), nuclear factor kappa beta (NF-kB), and tumor necrosis factor alpha (TNF-α). The particle size of the nanoconjugates was found to be in the range of 137.5 ± 7.9 to 298.4 ± 11.9 nm, and the zeta potential was 2.9 ± 0.1 to 26.9 ± 1.2 mV. The outcome of the MTT assay showed that curcumin-Phospholipon^®-scorpion venom (CUR-PL-SV) exhibited a satisfactory level of cytotoxicity, and the IC₅₀ was found to be lower than CUR and PL-SV individually. Cell cycle analysis showed predominantly cell cycle arrest at the G2-M and pre-G1 phases. In contrast, annexin V staining showed significant early and late apoptosis events in addition to increased necrosis when PC3 cells were treated with CUR-PL-SV. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed a reduction in expression of Bax, p53, caspase-3, NF-kB, TNF-α, and an increase in Bcl-2 expression. Moreover, a MMP analysis showed a reduction in mitochondrial permeability and hence confirmed the superior anticancer potential of CUR-PL-SV. Thus, the present study showed significant anticancer potency of SV-conjugated CUR phytosomes against human prostatic cancer PC3 cells, making it a novel treatment approach for PC.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"807-820"},"PeriodicalIF":6.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42082282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells.","authors":"Usama A Fahmy, Shaimaa M Badr-Eldin, Hibah M Aldawsari, Nabil A Alhakamy, Osama A A Ahmed, Mohamed F Radwan, Basma G Eid, Shaban R M Sayed, Gamal A El Sherbiny, Walaa Abualsunun","doi":"10.1080/10717544.2022.2072544","DOIUrl":"10.1080/10717544.2022.2072544","url":null,"abstract":"<p><p>Pancreatic cancer (PC) frequency and incidence have grown rapidly in recent years. One of the most serious problems with PC is the existence of asymptotic manifestations, which frequently delays early detection, and until the diagnosis is established, tumor cells progress to the metastatic stage. Another significant concern with PC is the scarcity of well-defined pharmacotherapeutic drugs. The aim of this study was to develop an efficient nanocarrier system to augment the efficacy of raloxifene (RLX) against PC cells. As a result, the current investigation was carried out in order to give an effective treatment method, in which an optimum RLX loaded phospholipid-based vesicles with melittin (PL-MEL) was chosen using experimental design software, with particle size, zeta potential and entrapment efficiency % as dependent variables. Furthermore, anticancer activity against PANC1 cells was assessed. The optimized nanovesicle parameters were 172.5 nm for the measured size, zeta potential of -0.69 mV, and entrapment efficiency of 76.91% that were in good agreement with the expected ones. RLX-raw, plain formula, and optimized RLX-PL-MEL showed IC₅₀ concentrations of 26.07 ± 0.98, 9.166 ± 0.34, and 1.24 ± 0.05 µg/mL, respectively. Furthermore, cell cycle analysis revealed that the nanovesicle was most effective in the G2-M phase, whereas Bax, and Bcl-2 estimates revealed that optimized RLX formula had the highest apoptotic activity among treatments investigated. However, as compared to RLX alone or plain formula alone, the optimized formula demonstrated higher expression of TNFα and Bax while a significant reduction of Bcl-2 and NF-κB expression was observed. mitochondrial membrane potential (MMP) analysis confirmed the apoptosis as well as the anticancer effect of the optimized formula. Thus, the present study results showed an improvement in the anti-PC effects of the RLX with phospholipid conjugated melittin, making it a novel treatment approach against PC.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1863-1877"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46570160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation of the novel structure curcumin derivative-loaded solid lipid nanoparticles: synthesis, optimization, characterization and anti-tumor activity screening <i>in vitro</i>.","authors":"Ke Li,&nbsp;Chao Pi,&nbsp;Jie Wen,&nbsp;Yingmeng He,&nbsp;Jiyuan Yuan,&nbsp;Hongping Shen,&nbsp;Wenmei Zhao,&nbsp;Mingtang Zeng,&nbsp;Xinjie Song,&nbsp;Robert J Lee,&nbsp;Yumeng Wei,&nbsp;Ling Zhao","doi":"10.1080/10717544.2022.2092235","DOIUrl":"https://doi.org/10.1080/10717544.2022.2092235","url":null,"abstract":"<p><p>This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity <i>in vitro</i>. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (<i>p</i> < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2044-2057"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9633707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLGA sustained-release microspheres loaded with an insoluble small-molecule drug: microfluidic-based preparation, optimization, characterization, and evaluation <i>in vitro</i> and <i>in vivo</i>.","authors":"Yue Su,&nbsp;Jia Liu,&nbsp;Songwen Tan,&nbsp;Wenfang Liu,&nbsp;Rongrong Wang,&nbsp;Chuanpin Chen","doi":"10.1080/10717544.2022.2072413","DOIUrl":"https://doi.org/10.1080/10717544.2022.2072413","url":null,"abstract":"<p><p>Microspheres play an important role in controlling drug delivery and release rate accurately. To realize the sustainable release of insoluble small-molecule drugs, a new three-phase flow-focusing microfluidic device was developed to produce the drug-loaded sustained-release microspheres which were prepared with bicalutamide (BCS class-II) as the model drug and poly(lactide-co-glycolide) (PLGA) as the carrier material. Under optimized prescription conditions, the microspheres showed a smooth surface and uniform size of 51.33 μm with a CV value of 4.43%. Sustained-release microspheres had a releasing duration of around 40 days <i>in vitro</i> without any initial burst release. The drug release mechanism of the microspheres was drug diffusion and polymer erosion. Meanwhile, the drug release of microspheres <i>in vivo</i> could be up to 30 days. Briefly, the microfluidic device in this study provides a new solution for the preparation of sustained-release microspheres for insoluble small-molecule drugs. PLGA sustained-release microspheres developed by the microfluidic device have good application prospects in precise delivery and sustainable release of insoluble small-molecule drugs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1437-1446"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of surfactant type on characteristics, skin penetration and anti-aging effectiveness of transfersomes containing amniotic mesenchymal stem cells metabolite products in UV-aging induced mice.","authors":"Andang Miatmoko,&nbsp;Nurul Ailda Marufah,&nbsp;Qothrin Nada,&nbsp;Noorma Rosita,&nbsp;Tristiana Erawati,&nbsp;Joni Susanto,&nbsp;Kusuma Eko Purwantari,&nbsp;Arif Nurkanto,&nbsp;Widji Soeratri","doi":"10.1080/10717544.2022.2149895","DOIUrl":"https://doi.org/10.1080/10717544.2022.2149895","url":null,"abstract":"<p><p>Transfersome has been developed to enhance dermal delivery of amniotic mesenchymal stem cell metabolite products (AMSC-MP). AMSC-MP contains many growth factors for managing skin aging, thus improving the quality of an adjusted life year. This study aims to determine the effect of surfactant types acting as the edge activator on transfersome-loading AMSC-MP. Transfersome was prepared by thin-layer hydration method and composed of l-α-phosphatidylcholine as a phospholipid and three types of surfactants, namely; cationic (stearylamine), anionic (sodium cholate), and nonionic surfactant (Tween 80) at a weight ratio of 85:15, respectively. Transfersomes were evaluated for physical characteristics, penetration, effectiveness, and safety. The results showed that sodium cholate, an anionic surfactant, produced the smallest transfersome particle size, i.e., 144.2 ± 3.2 nm, among all formulas. Trans-SA containing stearylamine had a positive charge of 41.53 ± 6.03 mV compared to Trans-SC and Trans-TW, whose respective charges were -56.9 ± 0.55 mV and -41.73 ± 0.86 mV. The small particle size and low negative value of zeta potential enabled high dermal penetration by transfersomes containing AMSC-MP, while the positive charge of stearylamine hindered its penetration of deeper skin layers. Trans-SC and Trans-TW produced higher collagen density values at 77.11 ± of 4.15% and 70.05 ± of 6.95%, than that of Trans-SA. All the AMSC-MP transfersomes were relatively safe with 0.5-1.0 macrophage cell numbers invaded the dermis per field of view. In conclusion, sodium cholate, an anionic surfactant, demonstrated considerable capacity as the edge activator of transfersome-loading AMSC-MP for skin anti-aging therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3443-3453"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/5d/IDRD_29_2149895.PMC9731583.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment.","authors":"Jieke Yan,&nbsp;Jing Guo,&nbsp;Yuzhen Wang,&nbsp;Xiaowei Xing,&nbsp;Xuguang Zhang,&nbsp;Guanghao Zhang,&nbsp;Zhaoqiang Dong","doi":"10.1080/10717544.2022.2118401","DOIUrl":"https://doi.org/10.1080/10717544.2022.2118401","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI) is one of the most common ischemic heart diseases. However, lack of sufficient drug concentration (in the ischemic heart) is the major factor of treatment failure. It is urgent for researchers to engineer novel drug delivery systems to enhance the targeted delivery of cardioprotective agents. The aim of the present study was to investigate the anti-AMI ability of calycosin (CAL) and tanshinone (TAN) co-loaded; mitochondrion-targeted tetrapeptide (MTP) and cyclic arginyl-glycyl-aspartic acid (RGD) peptide co-modified nano-system.: We prepared CAL and TAN combined lipid-polymer hybrid nano-system, and RGD was modified to the system to achieve RGD-CAL/TAN NS. MTP-131 was conjugated with PEG and modified onto the nanoparticles to achieve dual ligands co-modified MTP/RGD-CAL/TAN NS. The physicochemical properties of nano-systems were characterized. The AMI therapy ability of the systems was investigated in AMI rats' model. The size of MTP/RGD-CAL/TAN NS was 170.2 ± 5.6 nm, with a surface charge of -18.9 ± 1.9 mV. The area under the curve (AUC) and blood circulation half-life (T_1/2) of MTP/RGD-CAL/TAN NS was 178.86 ± 6.62 μg·min/mL and 0.47 h, respectively. MTP/RGD-CAL/TAN NS exhibited the most significant infarct size reduction effect of 22.9%. MTP/RGD-CAL/TAN NS exhibited the highest heart accumulation and best infarct size reduction effect, which could be used as a promising system for efficient treatment of cardiovascular diseases.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2815-2823"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/c0/IDRD_29_2118401.PMC9487946.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10503938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment.","authors":"Eman Yahya Gaballah,&nbsp;Thanaa Mohammed Borg,&nbsp;Elham Abdelmonem Mohamed","doi":"10.1080/10717544.2022.2144543","DOIUrl":"https://doi.org/10.1080/10717544.2022.2144543","url":null,"abstract":"<p><p>Onychomycosis accounts for 90% of nail infections worldwide. Topical therapy provides localized effects with minimal adverse systemic actions, yet its effectiveness is limited by minimal drug permeation through the keratinized nail plate. Ciclopirox (CIX) is a FDA-approved broad-spectrum antimycotic agent. However, the complete cure with its nail lacquer (8% w/v) may continue for one year with a high cost. Therefore, poly lactide-co-glycolide (PLGA) nanocapsules (NCs) of CIX were prepared by nanoprecipitation and optimized through a 2³ factorial design to be incorporated into hydroxypropyl chitosan (HPCH) based nail lacquer. Nail hydration, <i>in vitro</i> nail absorption, minimum inhibitory concentration (MIC), inhibition zones and <i>ex vivo</i> fungal growth on nail fragments were evaluated. The optimized NCs of CIX based on 100 mg PLGA 2 A and lipoid S75 showed a mean diameter of 174.77 ± 7.90 nm, entrapment efficiency (EE%) of 90.57 ± 0.98%, zeta potential (ZP) of -52.27 ± 0.40 mV and a prolonged drug release. Nail lacquer of the optimized NCs exhibited a higher stability than NCs dispersion. Compared to CIX solution (1% w/v), the respective decrease in MIC for NCs and their lacquer was four- and eight-fold. The lacquer superiority was confirmed by the enhancement in the nail hydration and absorption by 4 and 2.60 times, respectively, relative to CIX solution and the minimal <i>ex vivo</i> fungal growth. Therefore, HPCH nail lacquer of (1% w/v) CIX-PLGA-NCs can be represented as a potential topical delivery system for enhanced in vitro nail absorption and therapeutic efficacy against onychomycosis at a low dose.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3304-3316"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An icaritin-loaded microemulsion based on coix oil for improved pharmacokinetics and enhanced antitumor efficacy.","authors":"Huating Zeng,&nbsp;Xiaoqi Li,&nbsp;Yuping Liu,&nbsp;Xia Li,&nbsp;Ding Qu,&nbsp;Yan Chen","doi":"10.1080/10717544.2022.2147601","DOIUrl":"https://doi.org/10.1080/10717544.2022.2147601","url":null,"abstract":"<p><p>Combinational icaritin (IC) and coix seed oil (CSO) holds promising potential in the treatment of hepatocellular carcinoma. However, traditional cocktail therapy is facing difficulties to optimize the synergistic antitumor efficacy due to the asynchronous pharmacokinetics. Therefore, we developed an icaritin-loaded microemulsion based on coix seed oil (IC-MEs) for improved pharmacokinetics and enhanced antitumor efficacy. The preparation technology of IC-MEs was optimized by the Box-Behnken design and the pharmaceutical properties were characterized in detail. IC-MEs show synergistic antiproliferation against HepG2 cells compared with monotherapy. The mechanism is associated with stronger apoptosis induction via enhancing caspases-3 activity. IC-MEs significantly improve the bioavailability of IC due to the encapsulation of coix oil-based microemulsion and also obtain the desired liver accumulation and elimination. More importantly, IC-MEs exhibit the overwhelming antitumor ability among all of the treatments on the HepG2 xenograft-bearing mice. This study verifies the feasibility of using coix oil-based microemulsion to improve the antitumor effect of water-insoluble components.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3454-3466"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10602112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}