CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Runze Zhou,Zhi Xiao,Tianchi Lu,Yaqi Zhang,Ting Liu,Liping Hu,Xing Lu,Feifei Wang,Luyong Zhang,Huixia Lv
In vitro permeation test (IVPT) is a critical part of the prescription screening and evaluation of topical/transdermal drug delivery systems, in which ex vivo human skin or animal skin are generally used as skin membranes. The development of skin equivalents to replace animal/ human skins has high scientific and industrial value owing to the issues such as ethical issues and large variability of real skin. Here, a double-layer skin equivalent (DSE) containing both dermal-simulating structure and epidermal barrier function was developed. The dermal structure was composed of photo-crosslinked glycosaminoglycan, calcium alginate and gelatin; while the epidermal barrier-simulating structure was an electrospun nano-polyurethane-membrane. Mainly contributed to the synergistic effect of polysaccharide and protein composites, the formed DSE had similar compression modulus to that of real full-layer skin. Most of all it exhibited high correlation and similar transdermal drug release behavior with mini-porcine skin for three model drugs with different Log P. The DSE also showed comparable kinetic model fitting results to mini-porcine skin and exhibited a closer resemblance to porcine skin than other skin equivalents reported. Moreover, the penetration resisting ability of the DSE can be adjusted by adjusting the formulation to simulate different types of skin.
研究领域:
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 7
·2007
·
IF 5.4
Mengzhen Xing,Yuning Ma,Xiaocen Wei,Chen Chen,Xueli Peng,Yuxia Ma,Bingwen Liang,Yunhua Gao,Jibiao Wu
Poor transdermal permeability limits the possibility of most drug delivery through the skin. Auxiliary permeable microneedles (AP-MNs) with a three-dimensional network structure can effectively break the skin stratum corneum barrier and assist in the transdermal delivery of active ingredients. Herein, we propose a simple method for preparing AP-MNs using polyvinyl alcohol and Eudragit NM30D for the first time. To optimize the formulation of microneedles, the characteristics of swelling properties, skin insertion, solution viscosity, and needle integrity were systematically examined. Additionally, the morphology, mechanical strength, formation mechanism, skin permeability, swelling performance, biocompatibility, and in vitro transdermal drug delivery of AP-MNs were evaluated. The results indicated that the microneedles exhibited excellent mechanical-strength and hydrogel-forming properties after swelling. Further, it proved that a continuous and unblockable network channel was created based on physical entanglement and encapsulation of two materials. The 24 h cumulative permeation of acidic and alkaline model drugs, azelaic acid and matrine, were 51.73 ± 2.61% and 54.02 ± 2.85%, respectively, significantly enhancing the transdermal permeability of the two drugs. In summary, the novel auxiliary permeable microneedles prepared through a simple blending route of two materials was a promising and valuable way to improve drug permeation efficiency.Keywords:auxiliary permeation microneedles;polyvinyl alcohol;Eudragit NM30D;skin permeability;transdermal drug delivery
研究领域:
药剂学
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药物递送系统
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Biomaterials
·
2023
·Vol. 14
·期 5
·245
·
IF 4.8
Wei Cheng,Xue Wang,Shuai Zou,Mengfei Ni,Zheng Lu,Longfei Dai,Jiandong Su,Kai Yang,Xiaodong Su
Silicon microneedle (Si-MN) systems are a promising strategy for transdermal drug delivery due to their minimal invasiveness and ease of processing and application. Traditional Si-MN arrays are usually fabricated by using micro-electro-mechanical system (MEMS) processes, which are expensive and not suitable for large-scale manufacturing and applications. In addition, Si-MNs have a smooth surface, making it difficult for them to achieve high-dose drug delivery. Herein, we demonstrate a solid strategy to prepare a novel black silicon microneedle (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The proposed strategy consists of a simple fabrication of plain Si-MNs and a subsequent fabrication of black silicon nanowires. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching. The nanowire structures were then prepared on the surfaces of the plain Si-MNs to form the BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag+and HF concentrations during Ag nanoparticle deposition and [HF/(HF + H2O2)] ratio during Ag-catalyzed chemical etching, on the morphology and properties of the BSi-MNs were investigated in detail. The results show that the final prepared BSi-MN patches exhibit an excellent drug loading capability, more than twice that of plain Si-MN patches with the same area, while maintaining comparable mechanical properties for practical skin piercing applications. Moreover, the BSi-MNs exhibit a certain antimicrobial activity that is expected to prevent bacterial growth and disinfect the affected area when applied to the skin.Keywords:transdermal drug delivery;silicon microneedle;black silicon;Ag-catalyzed chemical etching;drug loading capacity
研究领域:
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 1
·169
·
IF 5.4
Yanping Fu,Chaonan Shi,Xiaodie Li,Ting Wen,Qiaoli Wu,Antian Zhang,Ping Hu,Chuanbin Wu,Xin Pan,Zhengwei Huang,Guilan Quan
Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs. The aggregation-caused quenching (ACQ) probes P4 emitted intense fluorescence signals in intact NC while quenched after the degradation of NC, had been demonstrated the feasibility of label intact NC. In this study, P4 was loaded in solid lipid nanoparticles (SLNs), and further encapsulated into DMNs, to track the transdermal diffusion of SLNs delivered at different skin sites. The results showed that SLNs had excellent stability after being loaded into DMNs with no significant changes in morphology and fluorescence properties. The in vivo live and ex vivo imaging showed that the transdermal diffusion rate of NC-loaded DMNs was positively correlated with skin thickness, with the order ear > abdomen > back. In conclusion, this study confirmed the site-dependency of transdermal diffusion in NC-loaded DMNs.Keywords:dissolving microneedles;solid lipid nanoparticles;in vivo fate;transdermal drug delivery;aggregation-caused quenching
研究领域:
药剂学
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生物医学工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yanyan Li,Kerong Chen,Yushuang Pang,Jiaxue Zhang,Ming Wu,Yurui Xu,Shitai Cao,Xinxin Zhang,Shaolei Wang,Yuping Sun,Xinghai Ning,Xiaoliang Wang,Desheng Kong
Additive manufacturing, commonly known as 3D printing, allows decentralized drug fabrication of orally administered tablets. Microneedles are comparatively favorable for self-administered transdermal drug delivery with improved absorption and bioavailability. Due to the cross-scale geometric characteristics, 3D-printed microneedles face a significant trade-off between the feature resolution and production speed in conventional layer-wise deposition sequences. In this study, we introduce an economical and scalable direct ink drawing strategy to create drug-loaded microneedles. A freestanding microneedle is efficiently generated upon each pneumatic extrusion and controlled drawing process. Sharp tips of ∼5 μm are formed with submillimeter nozzles, representing 2 orders of magnitude improved resolution. As the key enabler of this fabrication strategy, the yield-stress fluid inks are formulated by simply filling silica nanoparticles into regular polymer solutions. The approach is compatible with various microneedles based on dissolvable, biodegradable, and nondegradable polymers. Various matrices are readily adopted to adjust the release behaviors of the drug-loaded microneedles. Successful fabrication of multifunctional patches with heterogeneously integrated microneedles allows the treatment of melanoma via synergistic photothermal therapy and combination chemotherapy. The personalized patches are designed for cancer severity to achieve high therapeutic efficacy with minimal side effects. The direct ink drawing reported here provides a facile and low-cost fabrication strategy for multifunctional microneedle patches for self-administering transdermal drug delivery.
研究领域:
生物医学工程
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制药科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Xiaochang Liu,Peng Quan,Shanshan Li,Chao Liu,Yuan Zhao,Yongshan Zhao,Liang Fang
Chemical enhancers are widely used for facilitating drug penetration in transdermal drug delivery system (TDDS). However, there is a lack of knowledge about how the enhancement effect changes over time. In this study, on the basis of kinetic parameters of enhancement effect, molecular details of the dynamic enhancement process was described and a new hypothesis of the recovery mechanism of the skin barrier function was proposed. Using pretreated skin and flurbiprofen patch, the effects of Azone (AZ) and menthyl decanoate (MT-10) were evaluated with in vitro permeation experiment and further confirmed by confocal laser scanning microscopy (CLSM) and TEWL. The results showed that the enhancement ratio ( ER ) increased firstly, then reached a plateau and finally decreased. The enhancement effect of MT-10 was slower ( T onset, MT-10 > T onset, AZ ), weaker ( ER max, MT-10 < ER max, AZ ) and shorter ( T eff, MT-10 < T eff, AZ ) than that of AZ. According to the results of CLSM, ATR-FTIR and molecular dynamic simulation, the dynamic enhancement effect was caused by the variation of the diffusion coefficient of intercellular lipid in the stratum corneum (SC), which was dependent on the affinity between enhancers and lipid. Moreover, the skin barrier function recovered although a large amount of enhancers still existed in the SC. Additionally, according to the results of ATR-FTIR, molecular docking and skin retention study, the dynamic effect of AZ on the skin protein only induced skin irritation but showed no influence on drug penetration, so did the amount of the enhancer. In conclusion, dynamic enhancement effect was caused by the dynamic effect of the enhancer on the SC intercellular lipid, and the skin barrier function recovered by accepting the enhancer as a new component of the lipid bilayer .
研究领域:
药剂学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2017
·Vol. 15
·期 1
·1-15
·
IF 4.946
Yang Meng,Gu Yongwei,Yang Dishun,Tang Xiaomeng,Liu Jiyong
Background This work aimed to provide useful information on the use of nanoemulsions for the percutaneous administration of triptolide. Lipid nanosystems have great potential for transdermal drug delivery. Nanoemulsions and nanoemulsion gels were prepared to enhance percutaneous permeation. Microstructure and in vitro/in vivo percutaneous delivery characteristics of triptolide (TPL)-nanoemulsions and TPL-nanoemulsion gels were compared. The integrity of the nanoemulsions and nanoemulsion gels during transdermal delivery and its effects on the surface of skin were also investigated. The penetration mechanisms of nanoemulsions and nanoemulsion gels were investigated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The transport characteristics of fluorescence-labelled nanoemulsions were probed using laser scanning confocal microscopy. A chronic dermatitis/eczema model in mice ears and the pharmacodynamic of the TPL-nanoemulsion gels were also investigated.Results Compared to TPL gels, significantly greater cumulative amounts of TPL-nanoemulsion gels and TPL-nanoemulsions penetrated rat skin in vitro. The in vivo microdialysis showed the concentration–time curve AUC0–t for TPL-NPs is bigger than the TPL-gels. At the same time, TPL-NPs had a larger effect on the surface of skin. By hydrating keratin and changing the structure of both the stratum corneum lipids and keratin, nanoemulsions and nanoemulsion gels influence skin to promote percutaneous drug penetration. Both hairfollicles and the stratum corneum are also important in this transdermal drug delivery system. Moderate and high dosages of the TPL-nanoemulsion gels can significantly improve the symptoms of dermatitis/eczema inflammation and edema erythematic in mice ears and can reduce the expression of IFN-γ and IL-4. Moreover, the TPL-nanoemulsion gels cause less gastrointestinal damage than that of the Tripterygium wilfordii oral tablet does.Conclusion sNanoemulsions could be suitable for transdermal stably releasing drugs and maintaining the effective drug concentration. The TPL-nanoemulsion gels provided higher percutaneous amounts than other carriers did. These findings suggest that nanoemulsion gels could be promising percutaneous carriers for TPL. The TPL-nanoemulsion gels have a significant treatment effect on dermatitis/eczema in the mice model and is expected to provide a new, low-toxicity and long-term preparation for the clinical treatment of dermatitis/eczema in transdermal drug delivery systems.
研究领域:
药剂学
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药学
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药物递送系统
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 36
·18682-18691
·
IF 6.895
Kai Jiang,Yunsheng Chen,Di Zhao,Jin Cheng,Fangli Mo,Bin Ji,Chao Gao,Chuan Zhang,Jie Song
The transdermal drug delivery approach has been considered a potential therapy for human hypertrophic scars (HSs) instead of current uncomfortable surgical excision, local injection and laser therapy. However, a facile and efficient drug delivery method is urgently needed to overcome the skin barrier of transdermal administration. Herein, we employed a DNA-Fe nanoparticle delivery system via Fe ion driven self-assembly to satisfy the requirement of transdermal administration for HS therapy. Doxorubicin hydrochloride (DOX) as one of the widely used anticancer drugs was employed to treat the hyperplasia of abnormal skin fibrous tissue. Both in vitro and in vivo experiments of the DOX loaded DNA-Fe nanoparticles (DOX@DNA-Fe NPs) were performed to demonstrate the penetration ability, rapid drug release, and scar-inhibiting effects. This facile and efficient approach for HS therapy via a DNA-based transdermal drug delivery system may provide more possibilities for the development of transdermal administration.
研究领域:
药学
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纳米技术
·
皮肤病学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Jiesi Xie,Yujie Ji,Wei Xue,Dong Ma,Yunfeng Hu
A hyaluronic acid-containing ethosomes (HA-ES) as the transdermal drug delivery system was prepared in this work, and rhodamine B (RB) was used as a model drug to be encapsulated. The obtained HA-ES-RB was then characterized by the surface morphology, entrapment efficiency, drug loading and the stability. Results showed that the prepared HA-ES-RB was spherical and showed good dispersion as well as the stability, with a particle size of below 100 nm. The skin permeation experiments were carried out in vitro with the Franz diffusion cells and the rat dorsal skins were used. It was found that the penetration effect of HA-ES-RB was much better than that of ES-RB. The fluorescence microscopy image showed that HA-ES-RB penetrated into the deepest dermis. The excellent transdermic drug delivery effect of HA-ES-RB maybe attributed from its smaller size, hydration of hyaluronic acid as well as greater potential targeting to skin and skin appendages of liposomal carriers. Moreover, the HA-ES delivery system showed non-cytotoxicity to normal cells, indicating a good biocompatibility. This work provded a hyaluronic acid-containing ethosomes which can offer a quick, high efficient, safe and self-administered transdermal drug delivery system.
研究领域:
药剂学
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药物递送系统
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-15
·
IF 11.3
Shi Jiachen,Ma Qiuling,Su Wenting,Liu Congyan,Zhang Huangqin,Liu Yuping,Li Xiaoqi,Jiang Xi,Ge Chang,Kong Fei,Chen Yan,Qu Ding
Background Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration.Methods In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the “one-step micro-molding” method for boosted transdermal and tumoral delivery of cannabidiol (CBD).Results Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a “one stone, two birds” strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo.Conclusion sThis study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.
研究领域:
药学
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生物医学工程
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肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shulin Shen,Aiqun Wan,Yan Wang,Linxiao Liu,Yao Yao,Jiaqi Weng,Tong Zhu,Qingliang Yang,Qinying Yan
Transdermal drug delivery systems for rheumatoid arthritis (RA) have garnered substantial attention due to their great potential to overcome limitations observed in conventional oral or injection strategies, including limited selectivity and adverse effects on extra-articular tissues. Microneedles (MNs) appear to be highly desirable carriers for transdermal drug delivery of RA. However, microneedles typically are unable to keep up with the flexibility of joints, which decreases the effectiveness of administration. In this study, we developed a flexible microneedles (FMNs) delivery system. And gelatin was employed for the fabrication of flexible backings for microneedles owing to its excellent ductility and biocompatibility . We achieved synergistic photothermal-chemotherapy of RA by incorporating the chemical drug Tacrolimus (TAC) and the photothermal agent gold nanorods (AuNRs) into dissolving microneedles. Results showed a high mechanical strength of the proposed FMNs. In the animal model of adjuvant-induced arthritis (AA), it is indicated that the prepared FMNs inhibited the expression of related inflammatory cytokines such as IL-1ß and TNF-α while enhancing bone repair and other related factors. Thus, the combination therapy of FMNs-mediated hyperthermia and chemotherapy can serve as a novel and synergistic treatment option for RA.
研究领域:
药学
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生物医学工程
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 32
·期 13
·2110746
·
IF 18.808
Lu Fan,Xiaoxuan Zhang,Min Nie,Ye Xu,Yuetong Wang,Luoran Shang,Yongxiang Zhao,Yuanjin Zhao
Microneedle (MN) patches are promising stratagems for transdermal drug delivery owing to its minimal invasiveness and portability. Particularly, separable MN patches attract more attention for durable and long-term drug delivery. Here, a new strategy for designing controllably separable MN patches by integrating photothermal responsive phase-changing microspheres (MPs) into conical hydrogel MNs, is presented. Such MPs consist of near-infrared (NIR)-responsive black-phosphorus (BP) and phase-changing gelatin (GT), and are fabricated using a simple capillary microfluidic device. When the composite MN patch is exposed to NIR, the contained BP/GT MPs can transform light into heat, increase local temperature, turn into a liquid state, and form cavities in MNs, resulting in the convenient detachment of the backing plate and the needles by shear force. Subsequently, the embedded needles can sustainably release the drug. In addition to intelligently controlling the detachment of MNs, the BP/GT MPs can load macromolecular drugs and release them in response to NIR stimulation. Results further demonstrated that such controllably separable MN patch can effectively load and release two drugs to ameliorate disease progression for systemic lupus erythematosus treatment. These features indicate the practical values of controllably separable MN patches for versatile drug delivery and clinical applications.
研究领域:
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）