Improved metabolic stability and therapeutic efficacy of a novel molecular gemcitabine phospholipid complex

Dora, Chander Parkash; Kushwah, Varun; Katiyar, Sameer S.; Kumar, Pradeep; Pillay, Viness; Suresh, Sarasija; Jain, Sanyog

doi:10.1016/j.ijpharm.2017.07.060

Cited by 42 publications

(35 citation statements)

References 44 publications

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“…ATC–phospholipid complex was prepared according to previous study with modification . Briefly, ATC (0.25 mmol) and ovolecithin with 1:1 molar ratio were placed into a 100 mL round-bottom flask and dissolved by 50 mL of anhydrous ethanol.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…ATC−phospholipid complex was prepared according to previous study with modification. 25 Briefly, ATC (0.25 mmol) and ovolecithin with 1:1 molar ratio were placed into a 100 mL round-bottom flask and dissolved by 50 mL of anhydrous ethanol. This mixture solution was then stirred for 2 h under nitrogen atmosphere at 40 °C, and the solvent was removed by vacuum rotary evaporation method at 40 °C for 1 h. The resulting ATC−phospholipid complex product was further dried using a vacuum drying oven and kept in a brown desiccator before use.…”

Section: Methodsmentioning

confidence: 99%

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Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

et al. 2018

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Water-insoluble drugs cannot be absorbed effectively through the gastrointestinal tract due to insufficient solubility and often face the problems of low bioavailability and poor therapeutic efficacy. To overcome these biopharmaceutical challenges, lipid-based formulations were suggested and have been researched in recent years. In this study, we used atorvastatin as a model drug to prepare a phospholipid complex prodrug system to upgrade its lipophilicity and further developed a drug loaded submicron emulsion to improve its in vivo bioavailability. The mean particle size and zeta potential of submicron emulsion were 122.7 nm and -22.7 mV. Intestinal absorption of atorvastatin from submicron emulsion was significantly improved compared with free drug, and the absorption rate constant ( K) and apparent permeability coefficients ( P) increase 2.88-fold and 2.45-fold, respectively. After oral administration, the atorvastatin plasma concentration of the emulsion group was much higher than that of free drug and the area under the curve (AUC) reached to 4.033 mg/L·h (2.58-fold). In vivo pharmacodynamics results revealed that atorvastatin submicron emulsion showed excellent antihyperlipidemia efficacy by reducing the total cholesterol, triglyceride, and low density lipoprotein cholesterol (LDL-cholesterol) levels and simultaneously increasing the high density lipoprotein cholesterol (HDL-cholesterol) level in comparison with Lipitor. In conclusion, drug-phospholipid complex loaded submicron emulsion was a promising oral delivery system for improving in vivo absorption behavior and therapeutic efficacy for water-insoluble drugs.

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Section: Materials and Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

et al. 2018

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“…This structure had a shielding effect on the drug molecules of heparin, such that the signals of heparin were not clearly displayed in the 1 H-NMR of the HEP-Pc complex. To a certain extent, it also affected the polar end of phospholipid molecules, and its corresponding signals became wider and weaker (3.5-4.5 ppm), while the nonpolar end of phospholipid molecules could rotate freely, such that its corresponding signals did not change [27].…”

Section: Nuclear Magnetic Resonance (Nmr) Analysismentioning

confidence: 99%

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

Qiu

Fan

Liu

et al. 2021

IJMS

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A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.

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“…(3)The combination of GLA to phospholipids can enhance the absorption of GLA through lymphatic pathway and may reduce the exposure of the GLA in the gastrointestinal tract and protect the GLA from degradation by the enzymes [37,38].…”

Section: Pharmacokinetic Studies In Dogsmentioning

confidence: 99%

Preparation and Evaluation of Glaucocalyxin A SustainedRelease Pellets Based on Phospholipid Complex System with Enhanced Bioavailability

2020

J Pharm Pharmacol

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Objective: Glaucocalyxin A (GLA) suffers from low oral bioavailability and rapid in vivo metabolism. Therefore, the purpose of this study was to develop a new formulation to enhance the oral bioavailability simultaneously sustained release of GLA.Material and methods: GLA-phospholipid complex was firstly formulated by solvent-evaporation method to improve the solubility of GLA. Differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, and solubility study were used to characterize the GLA-phospholipid complex. And then, the optimized GLA-phospholipid complex was selected to prepare GLA-phospholipid complex sustained release pellets by extrusion-spheronization and fluidized bed coating technology. The prepared pellets were studied by in vitro drug release study and administered to beagle dogs to evaluate the oral bioavailability of GLA-phospholipid complex and GLA-phospholipid complex sustained release pellets. Results:The results illustrated that GLA in GLA-phospholipid complex was either molecularly dispersed or in an amorphous form with 13.8fold water solubility than the free GLA. The pharmacokinetic studies in beagle dogs demonstrated that GLA-phospholipid complex and GLAphospholipid complex sustained-release pellets showed 2.19-fold and 2.07-fold improvement than the free GLA by oral dosage, respectively. Further, steady plasma concentration, and prolonger Tmax were simultaneously obtained from GLA-phospholipid complex sustained release pellet. Conclusion:These outcomes suggested that the combination of phospholipid complex and sustained release pellets could enhance the oral bioavailability and prolong the action time in vivo which provided a promising delivery system for GLA.

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Improved metabolic stability and therapeutic efficacy of a novel molecular gemcitabine phospholipid complex

Cited by 42 publications

References 44 publications

Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

Combination of Phospholipid Complex and Submicron Emulsion Techniques for Improving Oral Bioavailability and Therapeutic Efficacy of Water-Insoluble Drug

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

Preparation and Evaluation of Glaucocalyxin A SustainedRelease Pellets Based on Phospholipid Complex System with Enhanced Bioavailability

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