COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Yan Li,Sedrati Manar,Xinxiang Chai,Yanzhen Lou,Guohua Jiang
Microneedle technology has emerged as a potential new means of painless drug delivery for diabetic patients. Maintaining blood glucose levels (BGLs) within the normal range for a long time is important for people with diabetes. However, it is a new challenge to realize long-term therapy due to insufficient drug loading. In this study, a polymeric porous microneedle array with continuous micropores was prepared by combining the microtemplate method and pore-causing agent method. By changing the ratio of a pore-causing agent, the fluid uptake capacity and mechanical strength were adjusted to balance the trade-off between rapid imbibition and the mechanical properties of puncture. A special drug loading chamber was developed to realize a large package (135.69 mg) of metformin-loaded porous microneedle system. Experiments in diabetic rat models in vivo showed that the prepared porous microneedles can effectively puncture the skin and maintain stable BGLs up to 7 h × 5 cycles over five experimental cycles (108 h) without the risk of hypoglycemia. These results suggested that the high-dose polymeric porous microneedle-mediated metformin delivery system had the advantages of rapid response and durable release, and was a potential candidate for sustained-release transdermal drug delivery in patients with diabetes mellitus and even chronic conditions.
研究领域:
生物医学工程
·
药剂学
·
材料科学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Fangzheng Tong,Xuyang Zhang,Xuanwen Wang,Siying Liu,Xiaoliang Cui,Yajie Zhou,Gang Li,Jun Zhang
Despite the promising potential of digital light processing (DLP)─fabricated silk fibroin (SF) microneedles (MNs) in transdermal applications, their clinical translation faces two major challenges: insufficient manufacturing precision to achieve architectural resolution and inadequate mechanical strength to penetrate the epidermis effectively. To overcome these critical barriers, we developed a methacrylated silk fibroin (Sil-MA) bioink that combines high biocompatibility with enhanced printability. By systematically optimizing material formulation, printing parameters and MN geometry, we successfully fabricated DLP-printed Sil-MA MNs with precise architecture control and superior mechanical performance. These MNs demonstrated no cytotoxicity and enabled efficient transdermal delivery of three distinct dermatological therapeutics. Comprehensive in vitro and in vivo assessments indicated that the DLP-printed Sil-MA MNs also acted as mechanical stimulators, significantly promoting epidermal keratinocyte proliferation. This engineered platform offers a versatile strategy for developing multifunctional MN systems for therapeutic delivery and tissue engineering applications.
研究领域:
生物医学工程
·
材料科学
·
药剂学
·
皮肤科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Xuejiao Wang,Yinling Ma,Xiaodan Qi,Xi Ruan,Deying Cao,Feng Zhao
The development of dissolving microneedles (DMNs) has brought light to the transdermal delivery of biomolecules that are released into the skin through the rapid dissolution of the matrix material to enter the systemic circulation and exert therapeutic effects. Herein, we aimed to prepare, characterize, and analyze the effectiveness of a glucagon-loaded DMN system that rapidly increases blood sugar levels in rats with diabetic hypoglycemia. The stability and content of biological drugs following DMNs preparation was assessed using circular dichroism and bicinchoninic acid kit for protein determination kits(BCA kits). The maximum drug loading capacity of DMNs was approximately 140 μg in each patch, and the microneedles could be stored for up to 14 days under dry storage conditions. In vitro skin permeation studies were conducted using a Franz diffusion cell apparatus for glucagon-loaded DMNs. To investigate the efficacy of transdermal drug delivery, drug-laden DMNs were administered to rats with hypoglycemic diabetes. Compared to subcutaneous injections , microneedle drug release demonstrated comparable efficacy in raising blood glucose levels in vivo. Therefore, this study demonstrated that glucagon-loaded DMNs may be a promising approach for efficient transdermal drug delivery as an alternative to subcutaneous injection for the treatment of severe hypoglycemia in patients with diabetes.
研究领域:
药剂学
·
生物医学工程
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 2
·e0172043
·
IF 2.806
Jiyu Li,Bin Liu,Yingying Zhou,Zhipeng Chen,Lelun Jiang,Wei Yuan,Liang Liang
Microneedle arrays (MA) have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA) fabricated by modified metal injection molding (MIM) technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.
研究领域:
材料科学
·
医学工程
·
药物递送
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Wantong Zhao,Lin Ma,Song Guo,Jia Yan Liu,Jingshu Piao,Mingguan Piao
Domperidone (DMP) is an effective peripheral D2 dopamine receptor antagonist . It is commonly used in the treatment of nausea and vomiting caused by Parkinson's disease . An oral preparation, which is rapidly absorbed after administration, and reaches a peak plasma concentration within 15–30 min, is commonly used. However, owing to the “first-pass effect” of liver metabolism and intestinal wall metabolism, the oral bioavailability of domperidone is low, and the action period is long. Therefore, in the present study, spray drying and emulsion solvent evaporation were combined to prepare a coated microsphere preparation with sustained release effect, and a gel matrix was selected to prepare a sustained-release coated microsphere gel for transdermal drug delivery. The pharmacokinetic results showed that the transdermal sustained-release coated microsphere gel effectively increased the Tmax, Cmax, T 1/2 , and AUC compared with those of an oral DMP group ( P < 0.05), and the relative bioavailability was 3.2 times that of the oral DMP group. This indicates that the preparation was able to ameliorate the problems associated with a traditional oral DMP formulation. Therefore, the present study may provide a theoretical basis for the transdermal delivery of DMP sustained-release microspheres.
研究领域:
药剂学
·
药物代谢动力学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Materials Express
·
2021
·Vol. 11
·期 7
·1101-1108
·
IF 0
Qian Min,Ma Di,Zhao Xiaoqi,Guo Wanxu,Zhang Yunfeng
Neonatal sepsis is a leading cause of neonatal mortality worldwide. Typically, intramuscular injections of gentamycin and vancomycin have been the preferred treatment for sepsis. The use of these drug molecules has many complications because of some side effects, proper dosage calculations,
and harmless injection supply. In the present study, we developed new combinations of therapeutic drug molecules containing anti-inflammatory curcumin with bioactive antimicrobial peptides (AMP). We designed and developed a biocompatible and thermally responsive chitosan/polyacrylamide polymeric
microneedle array to deliver AMP/curcumin nanoparticles (Nano-Cur) transdermally. The prepared drug-loaded microneedles were investigated for their chemical and morphological structure, in vitro insertion, and transdermal drug release. This investigation established that AMP/Nano-Cur-loaded
microneedles have potential effects in sepsis treatment.
研究领域:
医学
·
药剂学
·
生物材料
✓ 已验证
产品关联
DOI
COLLOID AND POLYMER SCIENCE
·
2018
·Vol. 296
·期 3
·471-481
·
IF 1.967
Han Lidong,Yang Rong,Yuan Shengxiao,Ding Shuang,Wu Ziheng,Wu Zhenghong,Qi Xiaole
Multiple emulsions are potential transdermal drug carriers for their remarkable ability to enhance skin permeability, but their intrinsic thermodynamically instability always limits further application. Here, we developed freeze-thawing water-in-oil-in-water multiple emulsion transdermal drug delivery system, which could accomplish solid-liquid transition in freeze-thawing cycles and keep stable under hypothermic storage (4 °C). In this study, freeze-thawing multiple emulsions were prepared by a two-step emulsification method with isopropyl palmitate as the oil phase, which could freeze at 4 °C to gain solid multiple emulsions and regain intact liquid emulsions at a shell temperature (32 °C) upon application on the skin. In vitro skin permeation studies on excised mice skin showed that the cumulative permeation percentages of diclofenac sodium from freeze-thawing multiple emulsions, multiple emulsions, and cream (Dakangfen®) were 41.22 ± 4.27, 36.63 ± 4.71, and 23.96 ± 3.49% separately. Moreover, pharmacokinetic experiments in rabbits indicated that the AUC 0 − t (area under the curve) of freeze-thawing multiple emulsions (30.872 ± 3.989 μg/mL h) and multiple emulsions (27.337 ± 2.804 μg/mL h) were significantly higher than those of the controlled cream (14.981 ± 1.331 μg/mL h) ( p < 0.05). These results suggested that freeze-thawing multiple emulsions could be a promising substitute of traditional multiple emulsions for transdermal drug delivery.
研究领域:
药剂学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2016
·
IF 2.641
Wei Weng,Peng Quan,Chao Liu,Hanqing Zhao,Liang Fang
The purpose of this work was to develop and design an appropriate drug-in-adhesive patch for transdermal delivery of risperidone (RISP). Various formulation factors were investigated by in vitro permeation study using excised rabbit skin. Increasing the drug concentration in the pressure sensitive adhesive (PSA) was used to enhance the drug permeation. To overcome the high crystallization tendency of the patch, several crystallization inhibitors such as PVP , PEG, and surfactants and fatty acids were evaluated by microscopy study. The mechanism of crystallization inhibition was investigated by differential scanning calorimetry , nuclear magnetic resonance spectrometer, and FT-IR studies. RISP and its active metabolite were determined after topical application of the optimized transdermal patch , and the in vivo pharmacokinetic parameters were compared with the intravenous administration group. The microscopy study indicated that fatty acid greatly inhibited the crystallization of RISP in PSA. The inhibition was attributed to the drug-additive interaction between amino group of RISP and the carboxyl group of fatty acid which was further confirmed by 1 H-NMR and FT-IR studies. The optimal permeation profile was obtained with the patches containing 5% RISP and 5% oleic acid in Duro-Tak ® 87-2287. The in vivo pharmacokinetic study exhibited a sustained absorption and metabolism profile and well correlated with the in vitro permeation data.
研究领域:
药剂学
·
药物传递系统
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Degong Yang,Xiaocao Wan,Peng Quan,Chao Liu,Liang Fang
Acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system (TDDS). However, there was little research about the quantitative relationship between drug release and drug-PSAs interaction. In this study, five acrylic PSAs with different molar fraction of carboxyl group were designed and synthesized. Propranolol (PRO) was used as model drug to evaluate release profiles in the PSAs in vitro and in vivo . The drug release percent in the PSAs were 81.66, 78.22, 51.66, 21.81 and 11.73%, and their release behaviors were decreased with carboxyl group content of PSAs. Furthermore, it was found that quantity of carboxyl group of PSAs was equal to residual drug by the quantitative determination. In addition, the ionic interaction between PRO and PSAs was confirmed by FT-IR and MDSC results qualitatively. Using the FT-IR, MDSC, Flory-Huggins interaction parameters and molecular dynamic simulation, interaction strength between drug and PSAs was determined quantitatively, which demonstrated that the drug release amount decreased linearly with interaction strength. Based on above results, we proposed that the PRO was possibly binding to the carboxyl group of PSAs one-by-one, which provided references for the accurate design of TDDS.
研究领域:
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Longyi Nan,Jie Liu,Chao Liu,Peng Quan,Jianpeng Guo,Liang Fang
Pressure-sensitive adhesives are critical to the product's safety, efficacy, and quality in transdermal drug delivery systems. However, many defects of transdermal patches ( e.g. , insufficient adhesion, patch displacement, and “dark ring” phenomenon) remain. Herein, the N -[tris(hydroxymethyl)methyl]acrylamide (NAT)-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) (AA-NAT/Fe 3+ ) was creatively proposed. Results demonstrated that the adhesiveness and cohesiveness of the optimized AA-NAT/Fe 3+ were higher by 1.8- and 9.7-fold, respectively, than those of commercially available DURO-TAK® 87-4098 due to the hydrogen bonding interaction of NAT-skin interface and coordination of NAT-Fe 3+ . Moreover, compared with that of DURO-TAK® 87-4098, the adhesion time of AA-NAT/Fe 3+ on the human forearm was remarkably prolonged, and no “dark ring” phenomenon was observed for AA-NAT/Fe 3+ after removal. After clonidine (CLO) was loaded into AA-NAT/Fe 3+ , controlled drug release and a drug transdermal behavior were endowed for CLO@AA-NAT/Fe 3+ in vitro and in vivo . AA-NAT/Fe 3+ still maintained superiority in adhesion and cohesion properties after CLO loading. These observations would contribute to the development of pressure-sensitive adhesives with outstanding adhesion and cohesion for transdermal patches. Statement of significance This N -[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) has enhanced adhesion and cohesion properties, which provide a simple but effective strategy to solve the problems ( e.g. , insufficient adhesion, patch displacement, and “dark ring” phenomenon) in existing transdermal patches.
研究领域:
材料科学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2017
·
IF 7.786
Chao Liu,Peng Quan,Shanshan Li,Yongshan Zhao,Liang Fang
Though acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system , molecular details of drug-PSA interactions, PSA molecular mobility variations and their influences on drug skin permeation are unclear. In this study, three classes of acrylic PSAs containing hydroxyl (AAOH), carboxyl (AACOOH) and non-functional group (AAnone) were synthesized. Their abilities of controlling drug release were evaluated using propranolol (PRO) and zaltoprofen (ZAL) in vitro and in vivo . Interaction details were identified by FT-IR, solid-state NMR and molecular modeling. Thermodynamic activity of drug and strength of drug-PSA interaction were characterized using miscibility study. PSA mobility was characterized using thermal analysis and rheology study. Thus, ionic interaction reduced the thermodynamic activity of PRO and mobility of AACOOH, which made PRO-AACOOH obtain a significant lower bioavailability (11.8 ± 0.7%) than these of PRO-AAnone (40.7 ± 2.5%) and PRO-AAOH (42.3 ± 2.9%). Though thermodynamic activity of ZAL in AACOOH was lower than that in AAOH due to the hydrogen bonding , bioavailability of ZAL-AAOH (19.0 ± 4.1%) exhibited no significant difference with ZAL-AACOOH (15.4 ± 2.8%), mainly because AAOH mobility was decreased by ZAL. In conclusion, the strength, types and involved functional groups of drug-PSA interactions were identified. On this basis, it was found that different control patterns of drug release were not only caused by the thermodynamic or kinetic hindrance effects of drug-PSA interactions, but also influenced by the interactions introduced PSA mobility variations, which was an innovative mechanism of controlled release in transdermal patch . The conclusions extended our understanding about the mechanism of controlled drug release of drug-in-adhesive patch. In addition, they contributed to the design of TDDS and custom acrylic PSAs.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 7
·1-10
·
IF 4.026
Lv Jianhua,Ou Xiaoyu,Fang Yaru,Wu Mi,Zheng Fanghao,Shang Lei,Lei Kaijun,Liu Yunen,Zhao Yan
Deep eutectic solvents (DESs) based on choline chloride (C) and l -(+)-tartaric acid diethyl ester (L) were prepared and used in transdermal drug delivery system (TDDS). The internal chemistry structure including the formation and changes of hydrogen bonds of choline chloride and l -(+)-tartaric acid diethyl ester DES was characterized via attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy. The stoichiometric ratio of choline chloride to l -(+)-tartaric acid diethyl ester as well as water content affected the viscosity, glass transition temperature ( T g ), and drug solubility of the DES. The viscosity and glass transition temperature of the DES (CL14) prepared at the ratio of 1:4 of choline chloride to l -(+)-tartaric acid diethyl ester were 1.19 Pa·s and − 44.01°C, respectively, and decreased to 0.10 Pa·s and − 55.31°C when 10% water (CL1410) was added. Taking diclofenac diethylamine (DDEA), the nonsteroidal anti-inflammatory drug as model, drug solubility was as high as 60 mg/ml and 250 mg/ml in CL14 and CL1410, respectively. The cumulative amount of DDEA was 4.63 ± 2.67 μg/cm 2 and 15.27 ± 4.63 μg/cm 2 for CL14 and CL1410, respectively, at 8 h. The mechanism of percutaneous permeability by the DES may be the disturbance of stratum corneum (SC) lipids as well as changes in the protein conformations. CL14 and CL1410 were also verified as low-cytotoxic and nonirritant. Therefore, the DESs studied are promising to be used in drug solubilization enhancement and transdermal drug delivery system. Graphical abstract
研究领域:
药剂学
·
生物医学工程
·
化学
✓ 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）