JOURNAL OF BIOMATERIALS APPLICATIONS
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2016
·
IF 1.988
Yanan Shi,Keke Li,Baocheng Tian,Maolei Xu,Qingzhi Lv,Juanjuan Zhao,Jingtian Han,Dongxiao Feng
Daily subcutaneous injection of human growth hormone has been used for the treatment of growth hormone deficiency and growth failure but has led to poor patient compliance and renal toxicity. Thus, it is crucial to develop favorable growth hormone delivery systems to improve patient compliance. In the present study, to increase the oral bioavailability of growth hormone and improve patient compliance, enteric-coated capsules filled with monomethoxyl poly(ethylene glycol)-b-poly(L-lactide-co-glycolide) nanoparticles were prepared to facilitate oral growth hormone delivery. The nanoparticles were less than 100 nm in size, exhibited narrow polydispersity indices < 0.3, and showed a zeta potential of −4.87 mV. The highest efficiency of growth hormone encapsulation achieved in this study was nearly 70%. An in vitro release experiment showed that adequate amounts of growth hormone were retained under simulated gastric conditions and significant amounts of growth hormone were released under simulated intestinal conditions. The bioavailability of encapsulated growth hormone relative to subcutaneously injected growth hormone in Sprague-Dawley rats was 11.06%. Thus, the use of poly(ethylene glycol)-b-poly(L-lactide-co-glycolide) nanoparticles yielded promising results, and these agents should be investigated further regarding their potential as an oral growth hormone delivery system in the future.
研究领域:
药剂学
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内分泌学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Tao Wang,Yunran Zhang,Meiling Chi,Chen Zhao,Linlin Cao,Chutong Tian,K. Kamei,Ying Zheng,Qikun Jiang
Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration, poor efficacy and side effects. Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution (FC-TNL) has the ability to treat glaucoma by lowering the intraocular pressure (IOP) with great efficacy and improving patient compliance. However, the commercialized netarsudil dimesylate precipitated when the pH of the solution was above 5.4, or when maleic acid, the salt of commercial timolol maleate, was mixed with netarsudil dimesylate. Consequently, the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in pH 4.8–5.2 solution by synthesizing timolol mesylate. Next, the morphology of timolol mesylate was observed by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and powder X-ray diffraction. The prepared FC-TNL showed good stability during refrigeration storage. Additionally, FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study. Importantly, once-daily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells. The FC-TNL was stable, safe and effective, being a promising glaucoma therapeutic.
研究领域:
药理学
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眼科医学
✓ 已验证
DOI
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2021
·Vol. 78
·期 4
·581
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IF 3.105
Wang Yue,Wang Joanne W.,Wang Yanbin,Yang Bing,Yinghua Du Alicia,Kong Ziqing,Chen Minglong,Wang Jie
Proper medication compliance is critical for the integrity of clinical practice, directly related to the success of clinical trials to evaluate both pharmacological-based and device-based therapies. Here, we established a liquid chromatography–tandem mass spectrometry method to accurately detect 55 chemical entities in the human urine sample, which accounting for the most commonly used 172 antihypertensive drugs in China. The established method had good accuracy and intraday and interday precision for all analyses in both bench tests and validated in 21 hospitalized patients. We used this method to monitor and ensure drug compliance and exclude the inferring impacts of medication compliance as a key confounder for our pivotal trial of a catheter-based, renal mapping and selective renal denervation to treat hypertension. It is found that in the urine samples from 92 consecutive subjects, 85 subjects (92.4%) were consistent with their prescriptions after 28 days run-in periods, 90 (97.8%) and 85 (95.5%) patients completely complied with their medications during the 3-month and 6-month follow-up period, respectively. Thus, using the liquid chromatography–tandem mass spectrometry method with specificity, accuracy, and precision, we ensured drug compliance of patients, excluded the key confounder of drug interferences, and ensured the quality of our device-based clinical trial for treatment of hypertension.
研究领域:
医学
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药理学
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临床研究
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jiao Xie,Xiaoguang Zhu,Meng Wang,Cheng Liu,Guixia Ling,Peng Zhang
Arthritis exerts a major impact on people's physical health and quality of life. Flurbiprofen axetil (FA), an effective non-steroidal anti-inflammatory drug for arthritis, has been limited due to its poor solubility. To boost therapeutic impact and broaden its applicability, we created FA-loaded liposomes (FA@Lipo) with an EE% of 75% via thin-film hydration sonication. Since joint injections or transdermal patches are typically used to treat arthritis, the former has poor patient compliance and the latter has limited transdermal efficacy. Therefore, considering these two aspects, we concentrated FA@Lipo and mixed it with the microneedle matrix to form FA@Lipo loaded soluble microneedles (FA@Lipo-DMNs), which could break through the skin barrier and deliver drugs effectively while reducing patient pain. In vivo pharmacodynamic experiments indicated that FA@Lipo-DMNs had similar therapeutic efficacy and less pain compared with subcutaneous injection (SC), which improved patient compliance. FA@Lipo-DMNs reduced the swelling and inflammatory factors level (TNF-α, IL-1β) of plantar and ankle joints significantly. Histological evaluation showed that FA@Lipo-DMNs could relieved arthritis effectively. All of these results all demonstrated the bright prospects of FA@Lipo-DMNs in the treatment of arthritis.
研究领域:
药剂学
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药物递送系统
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药理学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Meirong Yin,Yongnian Zeng,Han-Qing Liu,Wen Zhang,Chenyuan Wang,Chuang Chen,Wei Li
Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients’ self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.
研究领域:
药学
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生物医学工程
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皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Sida Ruan,Guiying Yang,Yuanzhen Dong,Wenwen Shangguan,Weigen Lu
Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1–84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1–84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1–34 analogue by increasing its affinity to albumin. Three PTH1–34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1–34 variants by using a solid–liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1–34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1–84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.
研究领域:
内分泌学
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药理学
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 5
·1704-1713
·
IF 7.59
Rui Wang,Han Wang,Guohua Jiang,Yanfang Sun,Tianqi Liu,Lei Nie,Amin Shavandi,Khaydar E. Yunusov,Uladzislau E. Aharodnikau,Sergey O. Solomevich
Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects upon oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug absorption, patient compliance, and fewer side effects. In this study, a new polymer microneedle (MN) system was developed for the transdermal delivery of AP to acute hyperuricemic mice. This study aims to achieve the controllable regulation of serum uric acid (SUA) levels with fewer side effects compared with oral administration. The matrix of polymer MNs consisted of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL), in which the rapid dissolution of PVP offers a rapid dissolution of AP into the blood and the biodegradability of PCL resulting in a sustainable drug release behavior. An in vivo study demonstrated that the AP-loaded MN system can effectively reduce the SUA levels as oral administration with lower side effects, which will be conducive to reducing the adverse reactions and improving the bioavailability of AP. This MN-mediated strategy can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia and improvement of patient compliance.
研究领域:
药剂学
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Huiyuan Yang,Xue Jiang,Yongnian Zeng,Wen Zhang,Qianqian Yuan,Meirong Yin,Gaosong Wu,Wei Li
Lactate is an important biomarker in sport medicine and clinical care. Conventional methods for lactate detection mostly rely on blood withdrawing which usually causes much pain, significantly reducing patient compliance. Here, we design a bilateral core-shell microneedle (MN) patch for measuring lactate level in skin with improved compliance and accuracy. The shell layer can rapidly absorb sufficient interstitial fluid (ISF) upon skin insertion, while the core layer selectively reacts with lactate in ISF and subsequently shows two visible color changes within a short time. In rats, the colorimetric patch allows determination of lactate-level changes over time after intensive exercise, which shows excellent agreement with lactate variation in blood, indicating admirable accuracy and sensitivity of lactate sensing of the bilateral core-shell MN patch. Furthermore, the MN-based sensor can recognize the abnormally increased lactate level in melanoma mice at early stage and distinguish it from the normal lactate concentration in healthy mice without driving tumor growth, suggesting a great potential for early tumors diagnosis in clinics.
研究领域:
运动医学
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临床护理
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生物传感器
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癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
Bioengineering & Translational Medicine
·
2024
·
IF 6.1
Huimin Li,Xueyu Wen,Xinyi Gong,Yange Wu,Puxuan Zhao,Yun Zhang,Zhuomin Sha,Hao Chang,Xuepeng Chen
Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra-pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline-loaded dissolvable microneedle (Mino-DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two-step casting micro-molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino-DMN patch features an array of minocycline-enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino-DMN inhibits pro-inflammatory factors, promotes anti-inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino-DMN offers a simple, efficient, user-friendly strategy for the adjunctive treatment of periodontal disease.
研究领域:
牙科
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药学
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生物医学工程
✓ 已验证
DOI
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Huijuan Zhou,Weina Yao,Qiujie Shan,Xiao Zhang,Dagan Zhang,Junyi Che,Feng Bai
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia in aged individuals. Galantamine hydrobromide (GAH) is an approved medication for AD that has been shown to significantly enhance cognitive function, effectively manage behavioral symptoms, and improve performance in essential daily activities. However, the side effects of these drugs include nausea and vomiting, significant fluctuations in blood concentration, and poor patient compliance. Therefore, improving the route of administration and enhancing therapeutic efficacy are major research focuses. Here, we propose the use of hierarchically structured hydrogel-encapsulated mesoporous silica nanocarriers (MSNs) to encapsulate GAH, with the goal of minimizing adverse reactions in the stomach. By enabling the slow release of the drug over an extended period, these hydrogels aim to reduce the frequency of dosing, thereby improving the efficiency of drug administration and enhancing patient compliance. Owing to these properties, drug-carrying microcapsules are capable of achieving optimal drug delivery and have emerged as excellent candidates for AD therapy. We believe that this technology has the potential to significantly impact clinical treatment.
研究领域:
药学
·
神经学
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纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Expert Opinion on Drug Delivery
·
2020
·
IF 4.838
Yidi Ma,Rou Guan,Shuying Gao,Wei Song,Yubo Liu,Yang Yang,Hongzhuo Liu
Introduction Everolimus (EVR) has been approved for the treatment of various advanced cancers and its indications are increasingly expanding. Therefore, it is crucial for patients who have difficulty in swallowing, such as pediatric and elderly patients, to obtain a convenient formulation. The oral absorption of EVR is limited due to its low solubility in water, intestinal metabolism by CYP3A4 enzyme, P-gp-mediated efflux, and metabolism in the liver. The aim of this study was to develop a novel sublingual orodispersible film loading everolimus for improving patient compliance and enhancing oral bioavailability of EVR.Research design and methods Sublingual orodispersible films loading EVR were prepared by the solvent casting method and evaluated by in vitro and in vivo studies.Results The properties of films were determined by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectrometry. The addition of acacia gum appeared to be crucial for protecting the drug from oxidation. Pharmacokinetic studies showed that loading into the sublingual orodispersible films significantly increased the oral bioavailability of EVR.Conclusion The EVR-loaded sublingual orodispersible films are a promising, economical, and convenient approach for delivering EVR efficiently in a solid dosage form.
研究领域:
药学
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2019
·
IF 4.153
Zhen Li,Meiqi Li,Bo Peng,Bingqing Zhu,Jian-rong Wang,Xuefeng Mei
Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen, has been prescribed for advanced breast cancer and prostate cancer. However, its poor compliance, reactive metabolite toxicity and hydrophobicity-induced drug accumulation has limited its applications. In this study, we aimed to modulate its dissolution rate and reduce reactive metabolites and drug accumulation through cocrystallization. Cocrystals of DES with isonicotinamide (INA), picolinamide (PIN), nicotinamide (NIA), urea (UREA), sarcosine (SAR), and flavone (FLA) were obtained. Different crystallization strategies result in cocrystal polymorphs for DES with INA and FLA. Intrinsic dissolution rate (IDR) characterizations in pH 2.0 buffer solution were conducted. Two assumptions (enhancing Cmax or prolonging Tmax) with the aim of improving compliance were put forward. On the basis of the IDR results (DES-NIA with a 1.5-fold increase in IDR and DES-2FLA-B with a 5.5-fold decrease in IDR) and the pharmacological activities of coformers (NIA and FLA with CYPs inhibition and UGTs stimulation effects), the pharmacokinetic behaviors of these two cocrystals were further researched. The 2-fold prolongation of Tmax in the PK profile DES-2FLA-B facilitated an improvement in compliance. In addition, the higher clearance rates and the potential to reduce oxidative metabolites in DES-2FLA-B help to decrease the drug accumulation and reduce the adverse effects of DES.
研究领域:
药学
·
药理学
·
化学
✓ 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）