Coatings
·
2022
·Vol. 13
·期 1
·23
·
IF 3.236
Shan Miao,Zheng Chen,Jin Wang,Shanbo Ma,Long Li,Yuhan Chen,Feiyan Wang,Meiling Zheng,Xiaodi Guo,Botao Song,Xiaopeng Shi
Oral instant membranes can be quickly wetted by the patient’s saliva and dissolved/disintegrated in the mouth without the need for drinking water and chewing, exhibiting great promise for patients from children to the elderly who have difficulties with swallowing. However, the reported instant oral membranes can load and release only one single drug, which greatly hinders their potential applications. Herein, we employ a sequential electrospinning approach to fabricate dual drug-loaded bilayered gelatin oral instant membranes. The results indicate that a gelatin membrane with a uniform nanofibrous structure can be successfully prepared, and that both the hydrophilic model drug and hydrophobic model drug can be embedded into the gelatin nanofibers. X-ray diffraction results verify that the two drugs are well distributed in the nanofibrous matrix in an amorphous state. Owing to the excellent water solubility and large surface area of gelatin nanofibers, the hydrophilic model drug can be quickly dissolved in 101 s, while the hydrophobic model drug can be completely released in 100 s. The bilayered gelatin nanofibrous membrane shows promise for simultaneous loading and release of two drugs for fast-dissolving delivery applications.Keywords:electrospinning;dual drug release;fast-dissolving;gelatin;bilayered structure
研究领域:
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Tingsheng Yan,Dalong Li,Jiwei Li,Feng Cheng,Jinju Cheng,Yudong Huang,Jinmei He
A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110 nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro . In simulated body fluid with 10 mM glutathione, the release rate in 12 h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Xianjing Zhou,Yanxin Qi,Zhijun Zhang,Jingjing Nie,Yubin Huang,Binyang Du
Novel engineered microgels with amphipathic network structures were designed and synthesized by copolymerizing N-isopropylacrylamide, 1-vinylimidazole, and 2-(cinnamoyloxy)ethyl methacrylate in the presence of 1,6-dibromohexane. The engineered microgels possess hydrophilic quaternization cross-linking structures and hydrophobic cross-linking inner nanodomains, which are suitable for loading and simultaneous release of hydrophilic nonsteroidal anti-inflammatory drug diclofenac sodium (DS) and hydrophobic antic cancer drug doxorubicin (DOX), respectively. The engineered microgels exhibited excellent stability, low cytotoxicity, and long blood circulation time and could be uptaken into the cytoplasm of cells, metabolized, and excreted from the living body by the kidney and the liver. In vivo experiments showed that with injection of DS and DOX dual-drug-loaded microgels, simultaneous antitumor treatment and inflammation depression were achieved along with high antitumor efficacy and low drug-related toxicity. Such microgels with amphipathic network structures have promising applications for combination therapy.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2022
·
IF 1.61
Hui-Xian Liu,Ge Cui,Dong-Lai Ma,Yue Zhang,Fei-Qun Xue
A series of novel pleuromutilin derivatives were designed and synthesized based on the twin drugs theory. Piperazinyl and thioether were used as the linkage to connect the pleuromutilin nuclear and sulfonamide to improve the biological activity and water solubility of derivatives. The in vitro antibacterial activities against drug-sensitive and drug-resistance bacteria were evaluated by agar dilution method. Most of the 25 compounds displayed excellent antibacterial activities against drug-sensitive bacteria, particularly, five compounds (9, 10, 11, 14a and 14b) exerted the excellent antibacterial activities against drug-resistance bacteria.
研究领域:
药物化学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Min Du,Jing Jin,Feng Zhou,Jiayue Chen,Wei Jiang
Antibacterial and hemostatic properties are essential for wound healing dressing. In this study, a new type of hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid-aldehyde (HA-CHO) is fabricated by photo-crosslinking and respectively loaded with a single drug gentamicin sulfate (GS), and two drugs of GS and lysozyme (LZM). The composite hydrogel of GelMA and HA-CHO is successfully synthesized by the aldehyde and Schiff base reactions. The structures and compositions of the hydrogels with and without drug loaded are characterized by FT-IR, 1 H NMR, and XPS. Furthermore, the microstructure and swelling behaviour of hydrogels prove that the content of HA-CHO has a significant role in the formation of hydrogels with dense porous structures and super absorbent. pH 7.4 and pH 5.0 conditions are used to evaluate the drug release behaviour of the obtained hydrogels. The released amount of GS of the drug-loaded hydrogels in the acidic buffer is more than that of the physiological environment because of the cleaved Schiff base bonds and the electrostatic interaction. Especially for the dual drug-loaded hydrogel GelMA/HA-CHO/GS/LZM, the released ratio of GS is elevated from 59 % in pH 7.4 buffer to about 78 % in pH 5.0 buffer within the first 6 h, which verifies the excellent pH-stimulus responsiveness. These endow the GS-LZM dual drug-loaded hydrogels with superior antibacterial efficiencies to that of the single GS drug-loaded hydrogels, no drug-loaded hydrogels, and SEBS control, especially in inhibiting S. aureus in a lower concentration of 10 6 CFU mL −1 , which can be attributed to the synergistic effect of LZM and GS. For S. aureus at 10 6 CFU mL −1 , the bacterial survival of GelMA/HA-CHO/GS/LZM is 1.1 %, which shows outstanding antibacterial effect . Hence, the drug-loaded hydrogels, especially the dual drug-loaded hydrogels with pH-responsive, antibacterial, and hemostatic properties have great potential as wound healing materials.
研究领域:
生物材料学
·
医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER TESTING
·
2022
·
IF 4.931
Yiyu Wang,Wenlong Yu,Chunqing Niu,Guiting Yu,Xin Huang,Jian Shi,Da Ma,Xuezheng Lin,Kai Zhao
Microspheres produced from biodegradable poly (D, L-lactic-co-glycolic acid) (PLGA) have been studied widely as drug delivery carriers for therapeutics. This study aimed to develop a near-infrared (NIR) light-activated PLGA microsphere loaded with two kinds of drugs with different molecular weights respectively or simultaneously by the double emulsion method (bovine serum albumin (BSA) and tetracycline hydrochloride (TH) as the drug model agents, indocyanine green (ICG) as the NIR responsive component). To optimize the incorporation of drugs and particle size for PLGA microspheres loaded single drug, the effect of three processing parameters, including the amount of polymer, initial ICG content, and initial BSA or TH content on the drug entrapment efficiency (EE), drug loading and the particle size were investigated. The PLGA microspheres were spherical and ranged from 5 to 10 μm in diameter. The EE of ICG and BSA in PLGA@ICG-BSA was 78.41 ± 0.71% and 69.88 ± 5.14%, respectively. The EE of ICG and TH in PLGA@ICG-TH was 71.52 ± 5.07% and 28.39 ± 3.39%. The PLGA microspheres exhibited desirable biodegradability and low cytotoxicity. Based on the optimized processing of single drug-loaded microspheres, dual-drug-loaded microspheres containing both large and small molecule drugs were further prepared. The EE of ICG, BSA, and TH was 83.37 ± 0.59%, 52.65 ± 3.48%, and 12.88 ± 2.53%; the particle size was ∼7.21 μm. All the NIR-responsive PLGA microspheres exhibited an efficient photothermal property and enhanced photothermal stability under multiple NIR irradiation cycles. The drugs from the different PLGA microspheres were released continuously over 18 days, mainly determined by Fick's diffusion. Furthermore, the drugs can be controlled released through a NIR light trigger, resulting in a dosage increase at a specific time point.
研究领域:
生物医学工程
·
药剂学
✓ 已验证
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Chang Wei,Xia Dong,Yan Zhang,Jie Liang,Afeng Yang,Dunwan Zhu,Tianjun Liu,Deling Kong,Feng Lv
Multispectral fluorescence imaging, from cellular imaging to in vivo imaging, represents a significant advancement for drug delivery research. Tracking multi-drug release using real-time imaging in vivo can reveal the release processes for guiding the design of an ideal drug delivery system to implement combination chemotherapy. Herein, a sustained and programmed drug delivery system was developed based on a PCL-PEG-PCL thermosensitive hydrogel combined with chitosan-multiwalled carbon nanotubes using doxorubicin (DOX) and rhodamine B (RB) as the model drugs. Dual drug delivery was monitored by fluorescence imaging at the cellular level, and in vivo fluorescence signals in nude mice were tracked by a multispectral fluorescence imaging system. The results demonstrated that the release of these two drugs can be dynamically tracked in vitro and in vivo, respectively using fluorescence imaging techniques. After loading onto carbon nanotubes, DOX exerted a significantly slower release rate compared with RB in the hydrogel due to the dual release of DOX. The hydrogel-carbon nanotube delivery system achieved programmed release of DOX and RB, which affirmed that it can be a potential drug delivery system with programmed release for combined administration.
研究领域:
生物医学工程
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Yiqing Liu,Peiyong Guo,Xinhao Dong,Yina Xu,Dan Li,Hua Zheng,Jianhong Liao
Here, we combined reversible addition-fragmentation chain transfer (RAFT) polymerization and amide coupling reaction to develop a novel drug-polymer conjugate using poly(AMA- co -IMMA)-b-poly(OEGMA) (termed as PAIPO) as nanocarriers. In order to enhance cellular uptake and obtain subsequent endo/lysosomal escape capacity, the dual-drugs-conjugated prodrug was then coupled with 2,3-dimethylmaleimide (DA) moieties and implanted with imidazolyl groups, respectively. Paclitaxel (PTX) was conjugated to PAIPO via 3,3′-dithiodipropionic acid (DPA) to construct a GSH-responsive moiety, while doxorubicin (DOX) was conjugated to PAIPO via 4-formyl benzoic acid to construct a pH-responsive moiety, which synergistically enabled a synchronized and precise drug delivery. The micelles self-assembled from DOX/ [email protected] DA showed an ideal average diameter (163.2–178.3 nm), contributing to passive targeting by the EPR effect. Moreover, a switch of the surface Zeta potential of micelles from steady negatively charged (− 9.74 ± 0.54 mV) at pH 7.4 to positively charged (+ 6.33 ± 1.25 mV) at pH 6.5, facilitated the long blood circulation and cellular endocytosis of micelles, respectively. More importantly, in vitro studies confirmed that DA M(DOX n /PTX) exhibited a strong synergism against tumor cells, and under slightly acidic conditions (pH 6.5), the combination index (CI) values for DA M(DOX 1 /PTX) on HeLa and Skov-3 cells were estimated to be 0.47 and 0.49 (previous to be 0.50 and 0.56 at pH 7.4), respectively. And in vivo results showed effective tumor accumulation potential, remarkable biosafety, and biocompatibility. Combined, such synchronized delivery approach based on multi-responsive micelles might potentiate the efficacy of combination chemotherapy in clinical cancer treatment.
研究领域:
药物递送系统
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
Polymer Chemistry
·
2019
·Vol. 10
·期 43
·5879-5893
·
IF 4.76
Jianhong Liao,Yajing Song,Can Liu,Dan Li,Hua Zheng,Bo Lu
Combination therapy and efficient delivery of two or more drugs into cancer cells to obtain a superior cell-killing performance is one of the major challenges of cancer therapy due to the pathological complexity, multi-drug resistance and inefficient cellular uptake. Herein, we employed reversible addition–fragmentation chain transfer (RAFT) polymerization to prepare poly(AMA-co-IMMA)-b-poly(OEGMA) (PAIPO) copolymers, and paclitaxel (PTX) and cis-platinum (Pt(II)) were then co-conjugated, thus developing a novel approach for prodrug-based combination chemotherapy. In addition, pH-sensitive charge-conversion, dual-redox dual-drug release behavior, cytotoxicity of micelles against two cancer cell lines (HeLa and Skov-3) and the synergistic effects of the dual-drug were evaluated. Accordingly, both free-(PTXn/Pt) and micelle-(PTXn/Pt) showed a synergism (combination index (CI) was always lower than 1), and (PTX0.2/Pt) and (PTX2/Pt) in the micellar form exhibited the strongest synergism against HeLa (CI = 0.37) and Skov-3 (CI = 0.41) cells, respectively. What's more, the cellular uptake and flow cytometric profiles displayed that an enhanced cellular uptake and endo/lysosome escape occurred owing to the charge-conversion of micelles and the proton sponge effect of imidazolyl moieties, respectively, thereby exhibiting a higher cell-killing performance. To the best of our knowledge, this is the first report on prodrug-based systems with charge-conversion for a co-delivery (PTXn/Pt) complex for combination cancer therapy.
研究领域:
癌症治疗
·
药学科学
·
聚合物化学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2017
·
IF 1.194
Wei Wang,Biyun Zhao,Xiangyang Meng,Pan She,Pantian Zhang,Yi Cao,Xuefei Zhang
The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer , named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs , i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1 H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
Polymers
·
2020
·Vol. 13
·期 1
·67
·
IF 3.426
Honglei Zhang,Yanjuan Wu,Xiao Xu,Chen Chen,Xiukun Xue,Ben Xu,Tianduo Li,Zhaowei Chen
The conventional mono-chemotherapy still suffers from unsatisfied potency for cancer therapy due to tumor heterogeneity and the occurrence of drug resistance. Combination chemotherapy based on the nanosized drug delivery systems (nDDSs) has been developed as a promising platform to circumvent the limitations of mono-chemotherapy. In this work, starting from cisplatin and curcumin (Cur), we prepared a dual drug backboned shattering polymeric nDDS for synergistic chemotherapy. By in situ polymerization of the Cur, platinum (IV) complex-based prodrug monomer (DHP), L-lysine diisocyanate (LDI), and then conjugation with a hydrophilic poly (ethylene glycol) monomethyl ether (mPEG) derivative, a backbone-type platinum (IV) and Cur linkage containing mPEG-poly(platinum-co-Cur)-mPEG (PCPt) copolymer was synthesized. Notably, the platinum (IV) (Pt (IV)) and Cur were incorporated into the hydrophobic segment of PCPt with the fixed drugs loading ratio and high drugs loading content. The batch-to-batch variability could be decreased. The resulting prodrug copolymer then self-assembled into nanoparticles (PCPt NPs) with an average diameter around 100 nm, to formulate a synergetic nDDS. Importantly, PCPt NPs could greatly improve the solubility and stability of Cur. In vitro drug release profiles have demonstrated that PCPt NPs were stable in PBS 7.4, rapid burst release was greatly decreased, and the Pt and Cur release could be largely enhanced under reductive conditions due to the complete dissociation of the hydrophobic main chain of PCPt. In vitro cell viability test indicated that PCPt NPs were efficient synergistic chemotherapy units. Moreover, PCPt NPs were synergistic for cisplatin-resistant cell lines A549/DDP cells, and they exhibited excellent reversal ability of tumor resistance to cisplatin. This work provides a promising strategy for the design and synthesis of nDDS for combination chemotherapy.Keywords:nanosized drug delivery system;dual drug;backboned;combination chemotherapy;polyprodrug
研究领域:
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yating Wu,Guihua Wei,Xin Cao,Ran Wang,Xue Gou
The healing of infected wounds is a complex and dynamic process requiring tailored treatment strategies that address both antimicrobial and reparative needs. Despite the development of numerous drugs, few approaches have been devised to optimize the timing of drug release for targeting distinct phases of infection control and tissue repair, limiting the overall treatment efficacy. Here, a stimuli-responsive microsphere encapsulating dual drugs was developed to facilitate differential drug release during distinct phases of antibacterial and repair promotion, thereby synergistically enhancing wound healing. Specifically, zeolite imidazolate backbone in poly (lactic-co-glycolic acid) (PLGA) microsphere was employed for the encapsulation of ciprofloxacin (CIP), responding to acidic environment of bacteria and releasing antibiotic for antibacterial therapy. Meanwhile, curcumin (CUR) encapsulated in PLGA exhibited a gradual release profile, contributing to synergistic antibacterial effects. During the tissue repair phase, near-infrared light stimulation of Fe 3 O 4 embedded in PLGA generated heat, elevating the temperature to the glass transition point of PLGA, which significantly enhanced the release of CUR thereby promoting tissue repair. In vitro experiments demonstrated that the release of CIP and CUR achieved significant antibacterial effects in the early stages of treatment. Additionally, CUR could effectively enhance fibroblast migration and proliferation. In vivo studies using a mouse abscess model revealed that the microspheres exhibited remarkable antibacterial and wound-healing capabilities, effectively enhancing the re-epithelialization of wound tissue and reducing the infiltration of inflammatory cells. This study provides novel strategies for constructing drug delivery systems that match dynamic stages of wound healing, offering improved therapeutic outcomes for infected wounds.
研究领域:
生物材料学
·
药物递送系统
·
伤口愈合研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）