JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2021
·
IF 3.981
Hongji Liu,Hongqing Lin,Zhengzheng Zhou,Liang Li
Bergenin ( BER ) is a bioactive compound used for the treatment of chronic bronchitis in China. However, its low solubility and permeation limits its oral bioavailability. In this study, a new BER : isonicotinamide ( ISN ) cocrystal (1: 1, molar ratio) was reported for the first time. BER-ISN shows better solubility and intrinsic dissolution rates (IDRs) in aqueous medias such as water, buffer solutions with pH = 1.2, 4.5, and 6.8 in comparison to BER monohydrate. For instance, the solubilities of BER-ISN and BER monohydrate in water were 3.72 ± 0.22 and 1.42 ± 0.006 mg/mL, respectively, showing 2.62 times improvement. IDRs of BER-ISN and BER monohydrate were 29.90 ± 0.04 and 18.64 ± 0.27 mg/min/cm 2 , respectively, which was consistent with the solubility results. To explain the solubility behavior, phase solubility diagrams of BER monohydrate, ISN and BER-ISN in three pure organic solvents (ethanol, isopropanol and ethyl acetate) were performed according to the solubility product ( K sp ) and complexes formation ( K 11 ) theory. The predicted solubilities are consistent with experimental solubilities considering complexation effects. The Hildebrand solubility parameter (HSP) calculations support the results. Thus, BER-ISN cocrystal (1: 1) with improved solubility is a good candidate for further formulation development.
研究领域:
药学
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生物化学
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DOI
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Yuqian Du,Chutong Tian,Menglin Wang,Di Huang,Wei Wei,Yan Liu,Lin Li,Bingjun Sun,Longfa Kou,Qiming Kan,Kexin Liu,Cong Luo,Jin Sun,Zhonggui He
Oligopeptide transporter 1 (PepT1) has been a striking prodrug-designing target. However, the underlying mechanism of PepT1 as a target to facilitate the oral absorption of nanoparticles (NPs) remains unclear. Herein, we modify Poly (lactic-co-glycolic acid) (PLGA) NPs with the conjugates of dipeptides (L-valine-valine, L-valine-phenylalanine) and polyoxyethylene (PEG Mw: 1000, 2000) stearate to facilitate oral delivery of docetaxel (DTX) to investigate the oral absorption mechanism and regulatory effects on PepT1 of the dipeptide-modified NPs. The cellular uptake of the dipeptide-modified NPs is more efficient than that of the unmodified NPs in the stably transfected hPepT1- Hela cells and Caco-2 cells, suggesting the involvement of PepT1 in the endocytosis of NPs. The internalization of the dipeptide-modified NPs is proved to be a proton-dependent process. Moreover, the L-valine-valine modified NPs with shorter PEG chain exhibit distinct advantages in terms of intestinal permeability and oral absorption, resulting in significantly improved oral bioavailability of DTX. In summary, PepT1 could serve as a desirable target for oral nanoparticulate drug delivery and the dipeptide-modified NPs represent a promising nanoplatform to facilitate oral delivery of hydrophobic drugs with low bioavailability.
研究领域:
药剂学
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纳米医学
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药物递送系统
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Yuting Li,Liyun Xing,Lingling Wang,Xi Liu,Licheng Wu,Mingjie Ni,Zhou Zhou,Lian Li,Xiuxiu Liu,Yuan Huang
Exosomes, as promising vehicles, have been widely used in the research of oral drug delivery, but the generally low drug loading efficiency of exosomes seriously limits its application and transformation. In this study, we systematically investigated the effects of drug loading methods and physicochemical properties (lipophilicity and molecular weight) on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions. Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method, drug lipophilicity, drug molecular weight and exosome/drug proportions. Of note, we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes, which was attributed to the efficient loading capacity and sustained release behavior. Furthermore, milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs (octreotide, exendin-4 and salmon calcitonin). Collectively, our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
研究领域:
药理学
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纳米医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2015
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IF 1.602
Xiaoming Zhang,Yuyang Tian,Jiangtao Jia,Tingting Zhang,Guangshan Zhu
In this paper we present three new cocrystals based on deferiprone which is the first oral medicine as iron chelator . Solitary deferiprone possesses some known problems due to its good solubility and frequent dosing side effects. For these three novel co crystals, deferiprone is the active pharmaceutical ingredient (API), p -hydroxybenzoic acid (1, C 7 H 9 NO 2 ·C 7 H 6 O 3 ), 2, 5-dihydroxybenzoic acid (2, C 7 H 9 NO 2 ·C 7 H 6 O 4 ) and maleic acid (3, C 7 H 9 NO 2 ·C 4 H 4 O 4 ) are used as cocrystal formers (CCFs), respectively. Their structures were characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) analysis, thermogravimetric analyses (TGA), differential thermal analysis (DTA), elemental analysis (EA) and infrared spectral analysis (IR). Single crystal X-ray diffraction demonstrates that all three cocrystals (1–3) possess strong hydrogen-bondings assembled through hydroxyl of API and carboxylic acids of CCFs. The PXRD results indicate their high purity of as-synthesized samples. TGA, DTA, EA, IR and dissolution study of API and cocrystals were also measured and discussed, respectively. The results suggest that the cocrystals exhibit low dissolution rates comparing with solitary deferiprone, which is very advantageous for the oral medicine with frequent dosing side effects.
研究领域:
药学
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材料科学
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产品关联
DOI
高影响因子
Animals
·
2022
·Vol. 12
·期 18
·2480
·
IF 3.231
Cheng Zhang,Weihao Li,Ligong Chen,Zhaoliang Chen,Xuejing Wang,Qianqian Xu,Hailong Zhang,Huan Chen,Juxiang Liu
Simple SummaryDeveloping safe and effective antibiotic growth promoters (AGPs) substitutes is particularly important to improve animal health and production performance. As an essential plant oil, the oregano oil's main bioactive substance is carvacrol, which has been proven to have antioxidant, anti-inflammatory, antibacterial, and antiviral properties. The sanguinarine from macleaya cordata is the primary bioactive substance. Sanguinarine has anti-tumor, immune-enhancing, antibacterial, and anti-inflammatory effects. However, it has not been reported whether the compatibility of oregano oil and macleaya cordata extract could produce better results. This study is the first to report the effect of oregano oil combined with macleaya cordata oral solution on the growth of broilers. The oregano oil combined with macleaya cordata oral solution significantly improved the growth performance of broilers. At the same time, serum biochemical indices, serum antioxidant indices, serum immune indices, serum cytokines, and intestinal morphology were significantly improved. In summary, our results demonstrated that the mixed solution of oregano oil and macleaya cordata has substantial potential to be an alternative to AGPs for broilers to reduce costs and improve benefits. This study provides basic data and technical support for further research.AbstractThe abuse of AGPs in animal husbandry has led to severe problems such as drug resistance and ecological, and environmental destruction, which seriously threaten human health and public health security. In recent years, extracts of oregano oil and macleaya cordata have become a hot spot in the research and application of AGP substitutes for their safety and high efficiency. This study is the first to report the effect of oregano oil combined with macleaya cordata oral solution on broiler growth performance. A total of 960 one-day-old broiler chickens were randomly divided into four treatment groups (240 chickens per group). Each treatment group was divided into six replicate groups (40 birds per replicate group). There were four groups in this study: the solvent control group, the oregano essential oil combined with macleaya cordata extract oral solution group (OS group), the oregano essential oil oral solution group (OEO group), and the macleaya cordata extract oral solution group (MCE group). Two chickens from each replicate group were collected and mixed into a composite sample. Six composite samples were obtained for each treatment group. The results showed that the oregano oil combined with macleaya cordata oral solution significantly improved the growth performance of broiler chickens. At the same time, serum biochemical indices, serum antioxidant indices, serum immune indices, serum cytokines, and intestinal morphology were significantly improved by the OS group. This study shows that oregano oil combined with macleaya cordata oral solution has substantial potential to be an alternative to AGPs for broilers.Keywords:oregano oil;macleaya cordata;oral solution;broilers;growth performance
研究领域:
动物科学
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药理学
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兽医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-15
·
IF 10.2
Bao Xiaoyan,Qian Kang,Xu Mengjiao,Chen Yi,Wang Hao,Pan Ting,Wang Zhengyi,Yao Ping,Lin Li
Background Oral administration offered a painless way and improved compliance for diabetics. However, the emerging GLP-1 analog peptide drugs for diabetes primarily rely on the injection route, and the development of oral dosage forms was hampered by the low oral bioavailability due to the structural vulnerability to digestive enzymes and molecule impermeability in the gastrointestinal tract. Results In this study, the non-covalent interaction between cholic acid (CA) and liraglutide (LIRA) was found and theoretically explained by molecular docking simulation. Formation of this physical complex of liraglutide and cholic acid (LIRA/CA Complex) reduced the self-aggregation of LIRA and accelerated intestinal epithelium penetration. By the anti-solvent method, LIRA/CA Complex was loaded into zein/rhamnolipids nanoparticles (LIRA/CA@Zein/RLs) with a loading efficiency of 76.8%. LIRA was protected from fast enzymatic degradation by the hydrophobic zein component. Meanwhile, Rhamnolipids, a glycolipid with surface activity, promoted endocytosis while also stabilizing the nanoparticles. The two components worked synergistically to ensure the delivery of LIRA/CA Complex to intestinal villi and improved oral absorption without disrupting tight junctions. LIRA/CA@Zein/RLs demonstrated a considerable intestinal epithelium absorption in mouse gastrointestinal section and a retention in vivo over 24 h, resulting in a significant and long-lasting hypoglycemic effect in Type 2 diabetes mice. Conclusion This study provided a promising oral delivery approach for LIRA and exhibited the potential for further translation into clinical application.
研究领域:
药学
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药物递送系统
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jiahao Li,Sharon Shui Yee Leung,Edwin Ho Yin Chan,Cuiping Jiang,Evelyn Tze Yin Ho,Zhong Zuo
Introduction Piperine, the major component in Piper retrofractum and Piper nigrum, had potential therapeutic effects on central nervous system diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy and fragile X-associated tremor/ataxia syndrome. However, its low aqueous solubility (0.04 mg/mL) limits brain uptake and pharmacological investigations at higher doses. In the current study, formulation strategies and routes of administration were assessed to enhance systemic and brain uptake of piperine.Methods Formulation of piperine nanoparticles (PIP NPs) was developed to enhance its solubility. PIP NPs were prepared using flash nanoprecipitation via a four-stream Multi-Inlet Vortex Mixer, employing an aqueous solution of poloxamer 188 and an ethanolic solution containing piperine and Eudragit L100-55. The process was optimized using the Design of Experiments to minimize the particle size and maximize the encapsulation efficiency of piperine. Additionally, we investigated the impact of administrating PIP NPs via oral and intranasal routes on its systemic and brain uptake.Results The optimized PIP NPs formulation exhibited a particle size of 171.45±2.38 nm, polydispersity index of 0.27±0.01, zeta potential of −43.71±5.11 mV, encapsulation efficiency of 92.49±1.92% and drug loading of 15.07±0.09%. Fourier-transform infrared spectroscopy confirmed the successful encapsulation of piperine into nanoparticles. The PIP NPs could significantly increase the aqueous solubility of piperine from 0.04 mg/mL to 52.31±0.9 mg/mL and release piperine with a 12.83-fold higher rate than that from piperine suspension. Both oral and intranasal administrations of PIP NPs to C57BL/6 mice at 20 mg/kg demonstrated an increase in AUC0-120min for both plasma (7.9–10 times) and brain (4.7–5.0 times) comparing to that from piperine suspension, with no significant difference between these two routes.Discussion Our findings suggested that increasing solubility rather than changing the administration route served as the most critical step to enhance the brain uptake of piperine.
研究领域:
药剂学
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神经科学
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药物代谢动力学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 10
·3726-3736
·
IF 6.6
Li Yang,Jun Guo,Liwen Wang,Sicheng Tang,Ai-fang Wang,Shengwu Zheng,Zhiyong Guo,Xingjie Zan
The oral delivery of protein-based drugs is of great significance, but faces various obstacles, including the deactivation of proteins by the low pH in the stomach and the high concentration of protease, poor transport through intestinal bio-barriers, etc. Herein, we present an acid-resistant metal–organic framework (MOF), NU-1000, in which insulin (Ins, a model protein) was loaded with high capacity (Ins@NU-1000) through the pseudo second-order kinetic model and Langmuir isotherm model. Ins@NU-1000 protects Ins from deactivation in the stomach acid environment and releases it in the intestine through the transformation of the micro-sized rod particles into spherical nanoparticles. Interestingly, the rod particles exhibit long-term retention in the intestine, and Ins is efficiently transported by the shrunk nanoparticles through intestinal bio-barriers and released into the blood, resulting in significant oral hypoglycemic effects (lasting more than 16 h after a single oral administration). Our findings demonstrate that switching the physical properties of the delivery vehicle, such as the shape and size, can contribute to the success of oral protein administration.
研究领域:
药学
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材料科学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Longxin Lin,Yaling Zheng,Caixia Huang,Lanlan Cai,Hua Zhang,Wen Xu,Xiaoying Wang,Wei Xu
Oral drug delivery with tumor-targeting treatment persists as a challenge. In this study, a mixed polymeric micelle (PM) delivery system was designed to overcome the barriers to oral administration for tumor-targeting delivery of paclitaxel (PTX) for breast cancer treatment. D-α-Tocopheryl polyethylene glycol 1000 succinate-modified carboxymethyl chitosan-rhein (TCR) conjugate and Biotin-polyethylene glycol 2000-Biotin (BPB) conjugate were mixed to form TCR-BPB PMs. The particle size and polydispersity index of optimized PTX-loaded TCR-BPB PMs (PTX/TCR-BPB PMs) was 195.90 ± 7.63 nm and 0.08 ± 0.00, with a drug-loading capacity of 41.94 ± 2.47 %. In simulated gastroenteric fluid and blood environments, the PMs presented a sustained-release manner. PTX/TCR-BPB PMs were taken up by Caco-2 and 4T1 cells and displayed strong cytotoxicity in a time- and concentration-dependent manner. PTX/TCR-BPB PMs significantly improved intestinal absorption of PTX. The pharmacokinetics, tissue distribution, and in vivo imaging indicated that PTX/TCR-BPB PMs could enhance oral bioavailability of PTX, prolong the retention time of PTX in the blood, and enhance PTX tumor-targeting ability. PTX/TCR-BPB PMs enhance the antitumor efficacy of PTX and reduce its toxicity in normal organs. Therefore, TCR-BPB PMs are expected to serve as delivery carriers for the oral and tumor-targeting delivery of hydrophobic antitumor drugs.
研究领域:
药剂学
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肿瘤学
·
生物材料
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产品关联
DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 11
·6287-6298
·
IF 3.049
Yuanfeng Wei,Jianjun Zhang,Yazhen Zheng,Yaxiang Gong,Meng Fu,Chengran Liu,Liang Xu,Changquan Calvin Sun,Yuan Gao,Shuai Qian
The present study aims to develop cubosomes with surface cross-linked chitosan for sustained drug delivery and enhanced oral bioavailability of vinpocetine (VPT). GMO based liquid cubosomes with VPT loading were prepared by the high pressure homogenization method. In order to enhance the anti-digestion effect, chitosan was cross-linked on cubosomes by the Schiff reaction, followed by solidification via spray drying. The obtained spray-dried cubosomes (chito-cubosomes) are spherical microspheres with nano-sized holes on the surface. After reconstitution, the particle size and zeta potential of chito-cubosomes were determined to be ∼250 nm and +35.9 mV, respectively. In comparison to unmodified liquid cubosomes, chito-cubosomes exhibited a significant anti-digestion effect with a typical sustained release profile. In comparison to a VPT suspension, liquid cubosomes showed a 2.5-fold higher Cmax and 3.0-fold higher AUC0–∞, while chito-cubosomes further enhanced bioavailability (5.0-fold) with prolonged MRT (2.2-fold) and delayed Tmax (2.8-fold). The results suggested that chito-cubosomes could be a promising drug carrier for enhancing oral absorption with sustained release behavior.
研究领域:
药剂学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Xiaoyan Wu,Weihong Ge,Tengfei Shao,Weijun Wu,Jian Hou,Li Cui,Jing Wang,Zhenghai Zhang
Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was −10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
MengYing Lei,Qing Chen,Yang Wang,Gang Wang
Oral absorption of carrier-free self-assembly nanoplatform was limited by mucus barrier, p-gp efflux and liver metabolism. In this study, Pip-Cur-TA nanoparticle were constructed by co-assembly of tannic acid, curcumin and piperine via inter-molecular hydrogen-bonded and π-π interaction to improve the oral chemotherapy. The optimized Pip-Cur-TA nanoparticle showed an average diameter of 60 nm with a drug encapsulation efficiency of 67.02 % and loading capacity of 61.37 %. Pip-Cur-TA nanoparticles showed pH-dependent drug release, mucosal adhesion, inhibition of p-gp and liver metabolism and improved membrane permeability. Oral Pip-Cur-TA nanoparticle produced high oral delivery efficiency and relative oral bioavailability of 12.84 % in rats, and further showed significant tumor inhibition on PC-3 tumor cells. These findings confirmed that Pip-Cur-TA nanoparticle might be a promising oral drug formulation for chemotherapy.
研究领域:
药剂学
·
肿瘤学
✓ 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）