RSC Advances
·
2017
·Vol. 7
·期 32
·19815-19827
·
IF 3.108
Liya Zeng,Xin Xin,Yalin Zhang
Nanoemulsions have attracted much attention due to their wide application in commercial industries such as pharmaceutics, food, beverages and skin care. Cremophor EL has been extensively used for emulsification, protection and solubilization of various lipophilic bioactive agents. However, their anaphylactoid hypersensitivity reactions are still challenging. Therefore, the aim of this study was to develop and characterize a promising, low-level Cremophor EL-stabilized o/w nanoemulsion using the spontaneous emulsification method for oral administration. From comparing the physicochemical properties (particle size and size distribution) of their emulsions, Cremophor has better emulsifying capacity than Tween and the droplet radius of emulsions can be reduced by increasing the surfactant concentration in current systems. The impact of various short-chain alcohols (C–OH < 5) on the formation and stability of nanoemulsions was also investigated to optimize the formulations. And there is a good correlation between nanoemulsion droplet size and the surfactant packing parameter (p). The smallest droplet size with the narrowest size distribution was produced by the system containing ethylene glycol as a cosurfactant. However, preparation of nanoemulsions with ethylene glycol was a time-consuming process since it was difficult to emulsify the water-induced gel-structure. Surfactant-to-oil mass ratio and surfactant-to-cosurfactant levels had to be optimized to produce fine droplets. Moreover, there was a linear relationship between the viscosity/log P value of alcohols and droplet size. Ostwald ripening was the dominant breakdown process of nanoemulsions obtained in the ethyl oleate/Cremophor EL–butanol (3 : 2)/water system. Ostwald ripening rate was increased with increasing surfactant concentration. Dilution (100×) of this system considerably improved their stability against droplet growth. This study demonstrated that alcohol addition might be a useful tool for preparing Cremophor EL-stabilized nanoemulsions for pharmaceutical applications.
研究领域:
药剂学
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化学工程
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生物医学工程
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产品关联
DOI
高影响因子
Current Drug Delivery
·
2022
·Vol. 19
·期 1
·32-40
·
IF 3.758
Guo Hejian,Yan Xuehui,Tang Hao,Zhang Xiaoyan
Background: Exenatide(EXE) is an anti-hyperglycemic agent approved for treating type 2 diabetes by the Food and Drug Administration(FDA). However, twice-daily injection of exenatide is inconvenient for most of the patients. Objective: In this study, biotinylated trimethylated chitosan(Bio-TMC)
based nanoparticles were proposed to promote oral absorption of exenatide. Realizing the oral administration of exenatide is very important to alleviate patient suffering and improve patient compliance. Methods: Bio-TMC was synthesized, and the chemical structure was characterized by
Fourier transform infrared (FT-IR) spectroscopy and 1H NMR spectroscopy. Nanoparticles were prepared through polyelectrolyte interaction in the presence of sodium Tripolyphosphate (TPP) and hydroxypropyl methylcellulose phthalate (HP-55). Formulations were physically and chemically characterized.
In vitro release was investigated in different pH media. In vivo antidiabetic activities of biotin modified and non-biotin modified chitosan were evaluated in db/db mice. Results: EXE-loaded Bio-TMC/HP-55 nanoparticles were spherical in shape with
a mean diameter of 156.2 nm and zeta potential of +11.3 mV. The drug loading efficiency and loading content were 52.38% and 2.08%, respectively. In vitro release revealed that EXE-loaded Bio-TMC/HP-55 nanoparticles were released faster in pH 1.2 than pH 6.8 (63.71% VS 50.12%),
indicating that nanoparticles have enteric characteristics. Antidiabetic activity study revealed that after oral administration to diabetic mice, the relative pharmacological bioavailability (FPharm%) of the biotin modified nanoparticles was found to be 1.27-fold higher
compared to the unmodified ones, and the hypoglycemic effect was also found to be better. Conclusion: Bio-TMC/HP-55 nanoparticles are feasible as oral drug carriers of exenatide and have the potential to be extended to other drugs that are not readily oral, such as monoclonal antibodies,
vaccines, genes, etc. These would be beneficial to the pharmaceutical industry. Further research will focus on the biodistribution of Bio-TMC/HP-55 nanoparticles after oral administration.
研究领域:
药剂学
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生物医学工程
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药物递送系统
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2016
·Vol. 18
·期 3
·586-594
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IF 1.954
Wang Yuanwen,Wang Shicheng,Firempong Caleb Kesse,Zhang Huiyun,Wang Miaomiao,Zhang Ya,Zhu Yuan,Yu Jiangnan,Xu Ximing
This study was aimed at preparing orally administered naringenin-loaded liposome for pharmacokinetic and tissue distribution studies in animal models. The liposomal system, consisting of phospholipid, cholesterol, sodium cholate, and isopropyl myristate, was prepared using the thin-film hydration method. Physicochemical characterization of naringenin-loaded liposome such as particle size, zeta potential, and encapsulation efficiency produced 70.53 ± 1.71 nm, −37.4 ± 7.3 mV, and 72.2 ± 0.8%, respectively. The in vitro release profile of naringenin from the formulation in three different media (HCl solution, pH 1.2; acetate buffer solution, pH 4.5; phosphate buffer solution, pH 6.8) was significantly higher than the free drug. The in vivo studies also revealed an increase in AUC of the naringenin-loaded liposome from 16648.48 to 223754.0 ng·mL −1 h as compared with the free naringenin. Thus, approximately 13.44-fold increase in relative bioavailability was observed in mice after oral administration. The tissue distribution further showed that the formulation was very predominant in the liver. These findings therefore indicated that the liposomal formulation significantly improved the solubility and oral bioavailability of naringenin, thus leading to wider clinical applications.
研究领域:
药剂学
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药物代谢动力学
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纳米医学
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DOI
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Xinyan Mao,Xinying Li,Wenjie Zhang,Lun Yuan,Lei Deng,Liming Ge,Changdao Mu,Defu Li
Bioactive peptide drugs are mostly delivered by parenteral administration, which brings great pain and risks to patients. Oral administration is an acceptable alternative form. However, peptide drugs are extremely sensitive to the strong acidic environment in the stomach after oral administration. They would be degraded by pepsin and trypsin in the gastrointestinal tract. Herein, we present microspheres for intestinal-targeted peptides drug delivery through oral administration. Sodium alginate was reacted with l-cysteine to bring it into thiol groups. Then sodium alginate-l-cysteine conjugates were mixed with native sodium alginate and emulsified by an improved method. Ca2+ was used to fix the emulsion to get the microspheres. Bovine serum albumin was used as the simulating drug to assess the feasibility of microspheres as intestinal delivery carriers. The results showed that the microspheres exhibited spherical properties and narrow size distribution. The drug-loading capacity of microspheres was not compromised after thiol-modification. It is interesting that the microspheres can maintain structural integrity and hold drugs in the strong acidic environment in the stomach. Conversely, the microspheres presented sustained intestinal-targeted drugs release ability as expected. Moreover, thiol-modification further improved the adherence ability of microspheres on the inner walls of the small intestine, which is good for enhancing drug permeability. In sum, the microspheres based on thiol-modified sodium alginate have promising applications as intestinal-targeted macromolecular drug carriers.
研究领域:
药剂学
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生物材料
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药物递送
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DOI
PubMed
Bioactive Carbohydrates and Dietary Fibre
·
2016
·
IF 0
Zhihua Wang,Yongbin Yan,Wei Li,Lihua Wang,Guoyuan Li,Caiqin Qin
Two kinds of water-soluble hydroxypropyl chitosan (HPCS) samples with different weight-average molecular weights ( M w ) (HHPCS for higher M w , 1.43×10 5 Da; LHPCS for lower M w , 5.71×10 3 Da) were used to investigate their absorption and distribution in mice by oral administration after being labeled by fluorescein isothiocyanate . The result of in vitro degradation showed that HPCS degraded more easily in the presence of lysozyme than in pepsin . After oral administration of HPCS, HPCS would undergo a series of degradation and absorption under the action of tissue cells and enzymes in the body. The absorption and distribution of HPCS in organ tissues was significantly influenced by its M w . With the decrease of M w , the absorption rate and amount of HPCS increased. In fact, only a small amount of HPCS and its catabolite with low M w was absorbed by the tissues, and most HPCS was metabolized and excreted out of body rapidly. Additionally, there was some accumulation of HPCS in liver, and so HPCS content in liver and kidney was higher. The whole HPCS plasma concentration was lower instead, due to rapid plasma clearance . The absorbed HPCS molecules still maintained a relatively higher concentration even after 16 h in the tested tissues. The research results gave some valuable data for the application of water-soluble chitosan in food and biomedicine , especially as a potential candidate for drug delivery systems.
研究领域:
生物医学
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药剂学
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食品科学
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DOI
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Huaqiao Tang,Min Xu,XueRong Zhou,Yuanli Zhang,Ling Zhao,Gang Ye,Fei Shi,Cheng Lv,Yinglun Li
In order to compare the detailed toxicity of nano‑copper and CuCl 2 ·2H 2 O (Cu ions) in vivo , the oral toxicity of four differently sized Cu particles (30 nm, 50 nm, 80 nm and 1 μm) on rats was investigated compared with CuCl 2 ·2H 2 O in acute exposure scenarios. We compared the acute LD 50 values and evaluated the kinetics of Cu following a single equivalent dose (200 mg/kg) of five Cu materials. Continuous gavage of nano‑copper for 7 days, the mortality rates, relative organ weights, and hematological, biochemical, and histopathologic characteristics of rats were examined. The results showed that the LD 50 values of Cu ions, 30 nm, 50 nm, 80 nm, and 1 μm copper particles were 359.6, 1022, 1750, 2075, and >5000 mg/kg, respectively. Physiological and biochemical indexes indicated that 80 nm nano‑copper (Cu NPs) produced the highest degrees of toxicity in short term. The liver and kidneys were the major organs most affected by Cu NPs, and also the target organs for Cu accumulation. The toxic effects of Cu ions are similar to those of nano‑copper, but they were not the same. Therefore, the toxic effect of nano‑copper is likely to be the result of the dual action of nano‑copper particles and copper ions. Collectively, the acute toxic effects produced by Cu NPs were highly correlated with particle size. Moreover, the toxic effects produced by repeated dosing differed from those produced by a single dose, and this may be due to organ targeting effects that are dependent on the size of the nano-particles.
研究领域:
毒理学
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纳米生物学
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环境科学
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DOI
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 73
·期 7
·937-946
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IF 3.765
Li Jing,Zhou Yingping,Aisha Mayinuer,Wu Jingyan,Wang Hongyun,Huang Fang,Sun Minjie
ObjectivesLoratadine is a selective H1 receptor inhibitor that has been widely used in the clinical treatment of allergic diseases. Here we aimed to develop a novel solid loratadine nanocrystal to increase the low and pH-dependent water solubility for bioavailability enhancement.MethodsLoratadine solid nanocrystal was developed through high-speed shear-high pressure homogenization followed by freeze-drying, which was further prepared into tablets through direct compression. The formulation and process parameter were screened. Furthermore, the characterization and oral bioavailability of loratadine nanocrystal were studied.Key findingsThe loratadine nanocrystal had the satisfactory particle size of 425.9 nm and great redispersibility, which was mainly attributed to the addition of Pluronic F127 and polyvinylpyrrolidone K17 as the stabilizer. The saturation solubility of the loratadine nanocrystal was increased to 3.81, 3.22 and 2.57-fold that of the crude drug in water, pH 6.8 and pH 4.5 buffer respectively. Furthermore, the pharmacokinetic studies in rats revealed that the AUC (0-∞) of the nanocrystal tablets was 2.38-fold that of raw tablets and 1.94-fold that of commercial tablets, respectively.ConclusionsThe nanocrystal tablets could significantly improve the oral bioavailability of loratadine, which would also be a promising approach to enhance the solubility of insoluble drugs.
研究领域:
药剂学
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药物递送
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生物药剂学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Fei Li,Yunlu Wei,Jing Zhao,Luyao Zhang,Quanhong Li
Orally administrated is the primary way of pumpkin polysaccharides intake, and this is the way that they elicit their multiple bioactivities. However, little is known about how those orally ingested polysaccharides work, and the pharmacokinetics of pumpkin polysaccharides after orally administrated has not been described. This study aimed to elucidate the pharmacokinetic information (the plasma concentration-time curve, tissue distribution, and excretion profiles) of the pumpkin polysaccharide (PPc) in vivo after oral administration. Results revealed that PPc could enter into the blood and exhibited a relatively long circulation in the blood with a mean residence time (MRT) of 7.45 h and presented a higher aggregation of PPc in the liver and kidneys. To obtain the visualization of the systemic circulation of PPc, in vivo imaging was used with near-infrared fluorescence (NIRF) imaging, which distributed into various tissues with different region of interest (ROI) values after oral administration. The in-depth understanding of oral delivery of PPc in vivo was provided, which will provide the instruction clinical medication and deepen the understanding of bioactivities mechanisms of oral pumpkin polysaccharides.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 11
·2145
·
IF 7.675
Yuanfang Chen,Yuwei Yang,Haikang Tang,Ziqi Zhang,Xiaoliang Zhou,Wenqing Xu
Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome.Keywords:ROS response;aminothiols;oral administration;radioprotection;intestinal damage
研究领域:
药理学
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放射生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2015
·
IF 4.383
Rong Lu,Shan Liu,Qilin Wang,Xia Li
Oral administration remains a significant challenge in regards to drugs with serious solubility and stability issues. This article aimed to investigate the suitability of nanoemulsions as oral carriers of stiripentol (STP), an acid-labile drug, for enhancement of stability and bioavailability. STP-loaded nanoemulsions (STP-NEs) were prepared by using a solvent-diffusion/ultrasonication technique. STP-NEs were characterized in a variety of ways such as by particle size, entrapment efficiency, in vitro drug release, and transmission electron microscopy. A bioavailability study was performed in rats after oral administration of either STP-NEs, or commercial formulation (Diacomit®). The resultant nanoemulsions were 146.6 nm in particle size with an entrapment efficiency of 99.47%. It was demonstrated that nanoemulsions significantly improved the biochemical stability and bioavailability of STP. The bioavailability of STP-NEs was up to 206.2% relative to Diacomit®. Nanoemulsions fabricated from poly(ethylene glycol) monooleate/medium-chain triglycerides exhibited excellent performance in drug stabilization and absorption enhancement. The results suggest that STP-NEs are a promising means to solve the problems associated with stability and solubility of STP.
研究领域:
药剂学
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药物传递系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Shengfeng Peng,Ziling Li,Liqiang Zou,Wei Liu,Chengmei Liu,David Julian McClements
There is great interest in developing colloidal delivery systems to enhance the water solubility and oral bioavailability of curcumin, which is a hydrophobic nutraceutical claimed to have several health benefits. In this study, a natural emulsifier was used to form sophorolipid-coated curcumin nanoparticles. The curcumin was loaded into sophorolipid micelles using a pH-driven mechanism based on the decrease in curcumin solubility at lower pH values. The sophorolipid-coated curcumin nanoparticles formed using this mechanism were relatively small (61 nm) and negatively charged (−41 mV). The nanoparticles also had a relatively high encapsulation efficiency (82%) and loading capacity (14%) for curcumin, which was present in an amorphous state. Both in vitro and in vivo studies showed that the curcumin nanoparticles had an appreciably higher bioavailability than that of free curcumin crystals (2.7–3.6-fold), which was mainly attributed to their higher bioaccessibility. These results may facilitate the development of natural colloidal systems that enhance the oral bioavailability and bioactivity of curcumin in food, dietary supplements, and pharmaceutical products.
研究领域:
食品科学
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药剂学
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营养学
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产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2016
·Vol. 70
·期 3
·531-538
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IF 1.67
Ge Yue-bin,Wang Zhi-gang,Xiong Ying,Huang Xian-ju,Mei Zhi-nan,Hong Zong-guo
Artemisia argyi leaf is a well-known species in traditional Chinese medicine. However, the anti-inflammatory and activating blood stasis activities of its essential oil (AAEO) have not been explored in vivo. The present study measured the contents of three chemical components by gas chromatography (GC). The anti-acute inflammatory effects of AAEO were investigated in dimethyl benzene, glacial acetic acid and carrageenan-induced animals through skin administration or by oral gavage, respectively. The effects of AAEO on haemorheology were studied in a rat acute blood stasis model. The contents of eucalyptol, camphor and borneol in AAEO were 254.4, 51.6 and 58.7 mg/g, respectively. All dosages of AAEO by skin administration significantly decreased the swelling in dimethyl benzene-induced ear oedema and carrageenan-induced paw oedema, and reduced the permeability in glacial acetic acid-induced abdominal blood capillary ( p < 0.01). Meanwhile, haemorheology indexes such as whole blood viscosity and the erythrocyte aggregation index significantly decreased only in the high dosage group. In addition, the effects of AAEO by oral gavage were weaker than skin administration at the medium dose in the experiments. It suggests that AAEO has better absorption bioavailability and pharmacological effects through skin administration due to the better skin permeability of essential oil than gastrointestinal absorption.
研究领域:
中药学
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药理学
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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）