ACS Applied Materials & Interfaces
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2023
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IF 9.5
Ning Duan,Li Mei,Liting Hu,Xiaoni Yin,Xiangyang Wei,Ying Li,Qinghua Li,Guiqiu Zhao,Qihui Zhou,Zhaodong Du
Retinal neovascularization (RNV) is a typical feature of ischemic retinal diseases that can lead to traction retinal detachment and even blindness in patients, in which the vascular endothelial cell growth factor (VEGF) plays a pivotal role. However, most anti-VEGF drugs currently used for treating RNV, such as ranibizumab, need frequent and repeated intravitreal injections due to their short intravitreal half-life, which increases the incidence of complications. Herein, a hydrogel intravitreal drug delivery system (DDS) is prepared by a dynamic Schiff base reaction between aminated hyaluronic acid and aldehyde-functionalized Pluronic 127 for sustained release of ranibizumab. The prepared hydrogel system named HP@Ran exhibits excellent injectability, self-healing ability, structural stability, cytocompatibility, and blood compatibility. According to an in vitro drug release study, the hydrogel system continuously releases the model drug bovine serum albumin for more than 56 days. Importantly, in an in vivo rabbit persistent RNV model, the HP@Ran hydrogel system continuously releases pharmacologically active ranibizumab for more than 7 weeks and also exhibits superior anti-angiogenic efficacy over ranibizumab treatment by decreasing vascular leakage and neovascularization at 12 weeks. Thus, the developed HP@Ran hydrogel system possesses great potential for intravitreal DDS for the treatment of RNV.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-17
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IF 9.429
Liu Yubo,Chen Xiaohong,Gao Yuhang,Yu Deng-Guang,Liu Ping
Background The diversified combination of nanostructure and material has received considerable attention from researchers to exploit advanced functional materials. In drug delivery systems, the hydrophilicity and sustained–release drug properties are in opposition. Thus, difficulties remain in the simultaneous improve sustained–release drug properties and increase the hydrophilicity of materials. Methods In this work, we proposed a modified triaxial electrospinning strategy to fabricate functional core–shell fibres, which could elaborate design of shell component for manipulating the sustained-release drug. Cellulose acetate (CA) was designed as the main polymeric matrix, whereas polyethylene glycol (PEG) was added as a hydrophilic material in the middle layer. Cur, as a model drug, was stored in the inner layer. Results Scanning electron microscopy (SEM) results and transmission electron microscopy (TEM) demonstrated that the cylindrical F2–F4 fibres had a clear core–shell structure. The model drug Cur in fibres was verified in an amorphous form during the X-ray diffraction (XRD) patterns, and Fourier transformed infrared spectroscopy (FTIR) results indicated good compatibility with the CA matrix. The water contact angle test showed that functional F2–F4 fibres had a high hydrophilic property in 120 s and the control sample F1 needed over 0.5 h to obtain hydrophilic property. In the initial stage of moisture intrusion into fibres, the quickly dissolved PEG component guided the water molecules and rapidly eroded the internal structure of functional fibres. The good hydrophilicity of F2–F4 fibres brought relatively excellent swelling rate around 4600%. Blank outer layer of functional F2 fibres with 1% PEG created an exciting opportunity for providing a 96 h sustained-release drug profile, while F3 and F4 fibres with over 3% PEG provided a 12 h modified drug release profile to eliminate tailing–off effect. Conclusion Here, the functional F2–F4 fibres had been successfully produced by using the advanced modified triaxial electrospinning nanotechnology with different polymer matrices. The simple strategy in this work has remarkable potential to manipulate hydrophilicity and sustained release of drug carriers, meantime it can also enrich the preparation approaches of functional nanomaterials. Graphical Abstract
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Xin Chen,Duanxiu Li,Yanwen Duan,Yong Huang
Drug co-amorphization is an emerging technology to improve the pharmacokinetic properties of drugs and overcome their side effects. Herein co-amorphization of sinomenine (SIN), an anti-rheumatoid arthritis alkaloid, and an antihistamine drug tranilast (TRA) was investigated for the sustained release of SIN and alleviating its histamine-release adverse reactions. The full co-amorphization of SIN-TRA was determined by powder X-ray diffraction and modulated temperature differential scanning calorimetry , while their CO 2 − and N + –H stretching vibrations in FTIR and protonated nitrogen signals in N 1s X-ray photoelectron spectra suggest the proton transfer between SIN and TRA. These intermolecular interactions could also be observed in their 1D and 2D NMR spectra. All co-amorphous samples exhibited sustained SIN release and excellent physical stability. Therefore, our study not only characterized the strong intermolecular interactions between SIN and TRA, but also discovered a promising drug combination strategy for the sustained release of SIN and reduction of its side effects.
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Pharmaceutics
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2022
·Vol. 14
·期 3
·603
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IF 6.525
Dandan Hu,Xin Chen,Duanxiu Li,Hailu Zhang,Yanwen Duan,Yong Huang
Matrine (MAR), oxymatrine (OMAR), and sophoridine (SPD) are natural alkaloids with varying biological activities; matrine was recently used for the treatment of coronavirus disease 2019 (COVID-19). However, the short half-lives and rapid elimination of these matrine-type alkaloids would lead to low oral bioavailability and serious side effects. Herein, resveratrol (RES) was selected as a co-former to prepare their co-amorphous systems to improve the therapeutic index. The formation of co-amorphous MAR-RES, OMAR-RES, and SPD-RES was established through powder X-ray diffraction and modulated temperature differential scanning calorimetry. Furthermore, Fourier transform infrared spectroscopy and NMR studies revealed the strong molecular interactions between resveratrol and these alkaloids, especially OMAR-RES. Matrine, oxymatrine, and sophoridine in the co-amorphous systems showed sustained release behaviors in the dissolution experiments, due to the recrystallization of resveratrol on the surface of co-amorphous drugs. The three co-amorphous systems exhibited excellent physicochemical stability under high relative humidity conditions. Our study not only showed that minor structural changes of active pharmaceutical ingredients may have distinct molecular interactions with the co-former, but also discovered a new type of sustained release mechanism for co-amorphous drugs. This promising co-amorphous drug approach may present a unique opportunity for repurposing these very promising drugs against COVID-19.Keywords:co-amorphous systems;sustained-release;COVID-19;matrine-type alkaloids;resveratrol
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Frontiers in Pharmacology
·
2023
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IF 5.6
Peng Xiong,Yang Yuping,Guo Chenqi,He Qin,Li Yan,Gong Tao,Li Jia
Berberine (BBR) has a long history of use in the treatment of Rheumatoid arthritis (RA) and is considered one of the most promising natural product for the treatment of RA. However, oral administration of berberine has low bioavailability and requires frequent administration, resulting in poor patient compliance. In this study, we developed a BBR-loaded phospholipid-based phase separation gel (BBR-PPSG) to achieve sustained drug release and long-term therapeutic effect. The stability of BBR-PPSG was verified and it was found that it can be stored for a long time. The pharmacokinetic study on rats and rabbits showed that BBR-PPSG not only achieved 1-month of sustained release, but also significantly increased the area under the curve (AUC) by nearly 9-fold and prolonged the half-life (t1/2) by 10-fold. By constructing rat and rabbit models of RA, we also proved that BBR-PPSG administration once a month effectively alleviated joint swelling, and significantly reduce TNF-α levels in AIA rats and OIA rabbits. Histopathological analysis of rabbit joint sections revealed that after intra-articular injection of BBR-PPSG, the synovial cell layer remained intact, while in the model group, the synovial cells were significantly reduced and exhibited necrosis. MicroCT data analysis showed that the values of Tb.N and Tb. Sp in the BBR-PPSG group were significantly better than those in the model group (p < 0.05). This study addressed the limitations of frequent administration of BBR by developing a phospholipid-based phase separation gel system for berberine delivery, achieving long-term sustained release. The BBR-PPSG demonstrated good biocompatibility, simple preparation and excellent stability, thus holding potential as a novel pharmaceutical formulation for RA treatment.
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COLLOID AND POLYMER SCIENCE
·
2021
·Vol. 300
·期 1
·1-10
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IF 1.931
Jiang Binbin,Li Ranhong,He Xu,Chai Yunlong,Chai Yuxin,Wang Yan
In this study, the pyraclostrobin@polydopamine-polyurea microcapsules (Pyr@PNPMC) with anti-photolysis and sustained-release properties were prepared by interfacial polymerization based on O/W Pickering emulsion templates. The effects of water–oil ratio, stirring speed, temperature, and polydopamine nanoparticles (PDANPs) content on the preparation of microcapsules were systematically investigated. Under this condition, the encapsulation efficiency of microcapsules could reach up to 77.7%. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) images indicated that Pyr@PNPMC were prepared successfully, and the microcapsules were a regular sphere with a large number of PDANPs attached to the dense inner layer. According to the results of sustained-release and anti-photolysis experiments, the release rate of Pyr@PNPMC was slightly faster than that of the pyraclostrobin@polyurea microcapsules (Pyr@MC). Under UV light exposure for 7 h, Pyr@PNPMC still retains 83% of the active ingredient, while for Pyr@MC nearly 75% of the active ingredient had been lost.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Qianyu Sun,Tianzhong Yuan,Gang Yang,Daliang Guo,Lizheng Sha,Rendang Yang
The solubility of cyclodextrin metal-organic frameworks (CD-MOFs) in aqueous media making it not suitable as sustained-release drug carrier. Here, curcumin-loaded CD-MOFs (CD-MOFs-Cur) was embedded in chitosan- graft -poly(lactic acid) (CS-LA) via a solid-in-oil-in-oil (s/o/o) emulsifying solvent evaporation method forming the sustained-release composite microspheres . At CS-LA concentration of 20 mg/mL, the composite microspheres showed good sphericity. The average particle size of CS-LA/CD-MOFs-Cur (2:1), CS-LA/CD-MOFs-Cur (4:1) and CS-LA/CD-MOFs-Cur (6:1) composite microspheres was about 9.3, 12.3 and 13.5 μm, respectively. The above composite microspheres exhibited various degradation rates and curcumin release rates. Treating in HCl solution (pH 1.2) for 120 min, the average particle size of above microspheres reduced 28.19 %, 24.34 % and 6.19 %, and curcumin released 86.23 %, 78.37 % and 52.57 %, respectively. Treating in PBS (pH 7.4) for 12 h, the average particle size of above microspheres reduced 30.56 %, 26.56 % and 10.66 %, and curcumin released 68.54 %, 54.32 % and 31.25 %, respectively. Moreover, the composite microspheres had a favorable cytocompatibility, with cell viability of higher than 90 %. These composite microspheres open novel opportunity for sustained drug release of CD-MOFs.
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FOOD CHEMISTRY
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2023
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IF 8.8
Dongyang Zhu,Wuchao Ma,Meilian Yang,Shuzhen Cheng,Ling Zhang,Ming Du
This study prepared osteogenic peptides (OPs) from cod meat by hydrolysis and subsequently encapsulated them in nanoliposomes (NLP) to enhance bioaccessibility. The characterization, stability, controlled release behavior and bioactivity of OPs-loaded nanoliposomes (OPs-NLP) were investigated as well. The highest loading capacity (27.32%) was achieved in NLP loaded with 6 mg/mL of OPs. The particle size, zeta potential, and encapsulation efficiency of OPs-NLP were 70.59 nm, −11.98 mV, and 75.24%, respectively. The interaction between OPs and empty NLP was through hydrogen bonding and hydrophobic. The OPs-NLP showed the greatest stability during storage at 4 °C. The in vitro release profile of OPs from OPs-NLP fitted a one-level kinetic model best. The osteogenic activity of OPs was unaffected by NLP encapsulation, and the bioaccessibility of OPs was notably improved. These findings suggest that OPs-NLP has the potential to be used in functional foods.
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Journal of Materials Chemistry B
·
2023
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IF 7
Wei Xiong,Lingmei Yuan,Jinyang Huang,Bin Pan,Ling Guo,Guowen Qian,Cijun Shuai,Zhikui Zeng
ABSTRACT： Many traditional Chinese medicines monomers, such as naringin (NG), can regulate the local immune microenvironment to benefit osteogenesis. However, the rapid release of NG in scaffolds severely influences the osteogenesis-promoting effect. Herein, NG was loaded into mesoporous bioglass (MBG) to achieve sustained release through physical adsorption and the barrier role of mesoporous channels, then MBG loaded with NG was added to poly (L-lactic acid) (PLLA) to fabricate composite scaffolds by selective laser sintering (SLS) technology. The results showed that the NG-MBG/PLLA scaffolds could continuously slow-release NG for 14 days compared with the NG/PLLA scaffolds, the cumulative release amount for the NG-MBG/PLLA scaffolds was 44.26%. In addition, the NG-MBG/PLLA scaffolds can promote the proliferation and osteogenesis differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs). Meanwhile, the composite scaffolds declined the reactive oxygen species (ROS) level of RAW264.7 under the stimulation of lipopolysaccharide (LPS) and significantly suppressed Interleukin- 6 (IL-6) and enhanced Arginase-1 (Arg-1) protein expressions. Moreover, calcium nodules and alkaline phosphatase productions of mBMSCs under macrophages-conditioned medium for the NG-MBG/PLLA group also evidently increased compared with the PLLA and MBG/PLLA groups. The NG sustained-released composite scaffolds with osteo-immunomodulation function have a great application prospect in the clinic.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2021
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IF 3.981
Jiahui Lu,Yanying Li,Anqiang Zhang,Weiming Liu,Xingli Wang,Fuming Zhang,Robert J. Linhardt,Zhibin Lin,Peilong Sun
In cancer therapy, there still remains great challenges such as controlling cancer metastasis and the side effects from chemotherapy. Many anti-cancer drugs have cytotoxicity to normal cell with a high concentration, on the other hand, the anti-cancer effect will not be ideal if it didn’t reach the effective concentrations. So there is a way to make balance between the cytotoxicity and effective concentrations, sustained release can not only prolong the duration of the effective concentration but also reduce the time of peak concentration. Herein, we designed a sandwich structured antitumor composite with a three-layer film including: i) the top and bottom layers of ethyl cellulose (EC) containing Ganoderma lucidum triterpenes (GLT); ii) the middle layer of polyvinyl alcohol (PVA) containing G. lucidum polysaccharides (GLP). The films were fabricated layer-by-layer using electrospinning with the aim of providing the sustained release of the antitumor activity of GLT and GLP for use in cancer therapy. This sandwich structured material has potential for sustained antitumor release, high loading capacity (1.6% for GLT and 7.9% for GLP) and large surface area. The morphology, structure, biocompatibility , and the release profile of the encapsulated GLP and GLT in this fabricated composite were characterized. The in vitro antitumor effects of this drug film were studied using carcinoma cells, as SGC-7901, A549, Hela and Caco-2, with the IC 50 of 51.2, 90.7, 93.0 and 21.7 μg/mL, respectively. In brief, this medical film achieved a good antitumor effect at the cellular level.
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Journal of Materials Research and Technology-JMR&T
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2020
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IF 5.289
Wenwen Guo,Xin Wang,Jiali Huang,Wei Cai,Junling Wang,Lei Song,Yuan Hu,Zhou Gui
Currently, aluminum phosphide tablets have been extensively used as fumigant for grain storage because they could release phosphine that shows highly efficient anti-microorganism. However, phosphine is highly toxic and flammable which usually causes production accidents. Therefore, this study aimed to develop a novel fumigant based on cinnamaldehyde and study its antimicrobial efficacy for grain storage. The novel fumigant tablet was composed of cinnamaldehyde, silica, citric acid and sodium bicarbonate. Results showed that mesoporous silica with ultra-high specific surface area (1036.5 m 2 /g) served as carrier for cinnamaldehyde. The mixture of citric acid and sodium bicarbonate reacted with moisture to generate carbon dioxide which was helpful to release cinnamaldehyde. As expected, the fumigant tablet displayed a sustained release effect. The in vitro culture experiments showed that cinnamaldehyde had high antimicrobial effect against five fungi including Aspergillus flavus , Aspergillus candidus , Aspergillus niger , Fusarium and Penicillium . In the accelerated mildew simulation experiment (temperature: 35 °C, humidity: 98%), the blank group without mildew preventive began to go mouldy after five days, the control group with only cinnamaldehyde became mildew one week later, whereas there was no visible mildew growth in the experimental group with the fumigant tablet after one week. The number of fungal colonies in the blank group and the control group after one week was 8.3 × 10 4 and 6.5 × 10 3 CFU/g, respectively, while there were no fungi detected in the experimental group. This cinnamaldehyde-based fumigant tablet is a green and safe mildew preventive, which provides an alternative solution to aluminum phosphide tablet for grain storage.
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Bioactive Materials
·
2021
·
IF 14.593
Yunfan Zhang,Xueyu Dou,Lingyun Zhang,Hufei Wang,Ting Zhang,Rushui Bai,Qiannan Sun,Xing Wang,Tingting Yu,Decheng Wu,Bing Han,Xuliang Deng
Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery. However, most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements. In the present study, we prepared a semi-interpenetrating network composite gel (CG) by incorporating short chain chitosan (CS) into a covalent tetra-armed poly(ethylene glycol) network. In addition to satisfying physicochemical, mechanics, biocompatibility, and cell affinity requirements, this CG easily encapsulated acetylsalicylic acid (ASA) via electrostatic interactions and chain entanglement, achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell (PDLSC) proliferation and osteogenic differentiation. In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model. This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1, which upregulated M2 macrophage recruitment and polarization in situ , indicating its appealing potential in bone tissue engineering.
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