DRUG DELIVERY
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2019
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IF 3.829
Jin Li,Tongjie Cheng,Qiang Tian,Ying Cheng,Lixia Zhao,Xingzhen Zhang,Yi Qu
As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.
研究领域:
药剂学
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眼科医学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2020
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IF 7.242
Yanyan Wang,Li Zhou,Lei Fang,Feng Cao
Efficient ocular drug delivery to the posterior segment of the eye by topical administration is a great challenge to pharmacologists. To explore drug delivery system of organic-inorganic hybrid nanocomposites for the efficient delivery of dexamethasone disodium phosphate (DEXP), a targeted hybrid nanocomposite based on layered double hydroxide (LDH) and functional carboxymethyl chitosan (CMCS) derivatives was designed. A special substrate of peptide transporter-1 (PepT-1) and glutathione was modified on CMCS. CMCS-glutathione-glycylsarcosine (CMCG-GS) and CMCS-glutathione-valyl-valine (CMCG-VV)-LDH hybrid nanocomposites were prepared and structurally confirmed. The in vitro experiments on human conjunctival epithelial cells showed noncytotoxicity (LDH concentration ≤100.0 µg/mL) and enhanced permeability for hybrid nanocomposites. Additionally, cellular uptake of the CMCG-GS-DEXP-LDH (10:1) nanocomposite eye drops involved clathrin-mediated endocytosis and PepT-1 mediated actively targeting transport. Results of the in vivo precorneal retention study showed an 8.35-fold, 2.87-fold and 2.58-fold increase of AUC 0– 6 h, C max and MRT for CMCG-GS-DEXP-LDH (10:1) hybrid nanocomposite eye drops, respectively, compared to that of the commercial product. Fluorescence imaging of fluorescein isothiocyanate isome (FITC)-loaded LDH hybrid nanocomposites demonstrated that FITC could diffuse into the choroid-retina with the shelter of LDH and CMCG-GS. The presence of a strong fluorescence signal of FITC-conjugated LDH hybrid nanocomposites in the sclera revealed that integral LDH nanocarrier reached the sclera. In the tissue distribution evaluation of rabbit's eyes, DEXP of CMCG-GS-DEXP-LDH (10:1) nanocomposites group retained in the target of the choroid-retina for 3 h with final concentration at 120.04 ng/g. Furthermore, the results of fluorescence imaging and tissue distribution suggested that the intraocular transport pathway for the hybrid nanocomposites is the conjunctival-scleral route. Consequently, the developed hybrid nanocomposites offer a simple and efficient strategy for topically administered drug delivery to the posterior segment of the eye. Statement of Significance Efficient ocular drug delivery to the posterior segment of the eye by topical administration is a great challenge to pharmacologists. In this manuscript, hybrid nanocomposite based on layered double hydroxide (LDH) and functional carboxymethyl chitosan (CMCS) derivatives were designed. The multifunctional properties of these hybrid nanocomposites were attributed to active targeting, bioadhesive capacity and penetration enhancement. Visualization of transport routes of fluorescein isothiocyanate-conjugated LDH hybrid nanocomposites demonstrated that the integral LDH nanocarrier reached the sclera through the conjunctival-scleral pathway, and the loaded drug could further diffuse to the retina. The multifunctional CMCS derivatives-LDH hybrid nanocomposites could be applied for the efficient drug delivery to the posterior segment of the eye through noninvasive topical instillation.
研究领域:
药学
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纳米医学
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眼部药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Xiao-Ling Zhang,Yu-Xin Yue,Yang Yang,An-Kang Ying,Rong Ma,Jie Chen,Fang-Yuan Chen,Xiao-Yun Hou,Yu-Chen Pan,Da-Zhuang Ren,Tao Yang,Zhi-Qing Li,Dong-Sheng Guo
Eye drops are envisaged as the most promising non-invasive formulation for the treatment of the ocular posterior segment diseases, while it is hindered by a series of complex ocular barriers, both static and dynamic in nature. In this context, we propose a single molecule nanomedicine based on host-guest chemistry to achieve highly efficient drug delivery targeted to ocular posterior segment. Sulfonated azocalix[4]arene (SAC4A) serves as the single molecule carrier, owing the multiple features of small size (24.0 Å in length, 21.2 Å in width, 14.8 Å in height with a Van der Waals volume of 930 Å 3 ), negative charge, hydrophilicity, loading universality and hypoxia-triggered release. As a proof-of-concept, an eye drop formed by the complexation of SAC4A with sunitinib (SUN) is prepared to treat wet age-related macular degeneration (wAMD). SAC4A successfully transports SUN to the ocular posterior segment (the amount of SUN reaching the retinal-choroid tissue in the SUN@SAC4A group was 2.47 times larger than that in the SUN group at 30 min), significantly enhancing its anti-choroidal neoangiogenesis effect of SUN to wAMD, which played a key role in the treatment. We believe that the single molecule nanomedicine paradigm is highly amenable for treating various ocular posterior segment diseases in the future.
研究领域:
药学
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纳米技术
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眼科
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Jinhui Lu,Xiaomeng Zhu,Meng Zhang,Xunchan Jiang,Wei Guo,Feng Jiang,Feng Cao
Investigating the structural integrity of carriers in transit from ocular surface to ocular posterior segment is essential for an efficient topical drug delivery system. In this study, dual-carrier hydroxypropyl-β-cyclodextrin [email protected] ( [email protected] ) nanocomposites were developed for the efficient delivery of dexamethasone . Förster Resonance Energy Transfer with near-infrared I fluorescent dyes and in vivo imaging system were used to investigate the structural integrity of [email protected] nanocomposites after crossing Human conjunctival epithelial cells (HConEpiC) monolayer and in ocular tissues. The structural integrity of inner HPCD complexes was monitored for the first time. The results suggested that 23.1 ± 6.4 % of nanocomposites and 41.2 ± 4.3 % of HPCD complexes could cross HConEpiC monolayer with an intact structure at 1 h. 15.3 ± 8.4 % of intact nanocomposites could reach at least sclera and 22.9 ± 1.2 % of intact HPCD complexes could reach choroid-retina after 60 min in vivo , which showed that the dual-carrier drug delivery system could successfully deliver intact cyclodextrin complexes to ocular posterior segment. In conclusion, in vivo assessment of structural integrity of nanocarriers is greatly significant for guiding the rational design, higher drug delivery efficiency and clinical transformation for topical drug delivery system to the posterior segment of the eye.
研究领域:
药学
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眼科
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纳米技术
·
药物递送系统
✓ 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）