Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailab...Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.展开更多
Oral administration of nutrient/drug is the most common and preferred route. However, a number of barriers are encountered after ingestion, limiting efficient oral nutrient/drug absorption. Both lipid-based (e.g., nan...Oral administration of nutrient/drug is the most common and preferred route. However, a number of barriers are encountered after ingestion, limiting efficient oral nutrient/drug absorption. Both lipid-based (e.g., nanoemulsion, solid lipid nanoparticles) and polymer-based (e.g., protein and polysaccharide nanoparticles) nanoscale delivery systems have demonstrated capability to overcome some of these physiological barriers during transportation and metabolism stages. To better deal with those barriers, polymer-lipid complex nanoparticles are being explored and developed to merge the beneficial features and overcome the respective shortcomings of lipid-based and polymer-based nanoparticles. This paper aims to provide an overview of the various preparation strategies and supramolecular interactions of orally administered polymer-lipid complex nanoparticles by reviewing recent studies. Two types of polymer-lipid complex nanoparticles have been developed, i.e., lipid core with polymer shell nanoparticles and polymer core with lipid shell nanoparticles (lipid-polymer hybrid nanoparticles). Besides, both natural and synthetic polymers used for fabrication are discussed and their advantages and disadvantages are highlighted. Further research work is needed to optimize the fabrication and scaling up processes, so that these versatile polymer-lipid complex nanoparticles could have a significant impact on the oral delivery of nutrient/drug.展开更多
This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanop...This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.展开更多
基金This research is financially supported by the Natural Science Foundation of China(Grant No.81273446).
文摘Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.
基金This work was supported by the National Key R&D Program(No.2017YFA0204503)the National Natural Science Foundation of China(Nos.22071172,91833306,21875158,51633006,and 51733004)+1 种基金Z.F.thanks the funding support from ITC via Hong Kong Branch of National Precious Metals Material Engineering Research Center(NPMM),and the Start-Up Grants(Nos.9610480 and 7200651)Grant from City University of Hong Kong(No.7005512).
文摘Oral administration of nutrient/drug is the most common and preferred route. However, a number of barriers are encountered after ingestion, limiting efficient oral nutrient/drug absorption. Both lipid-based (e.g., nanoemulsion, solid lipid nanoparticles) and polymer-based (e.g., protein and polysaccharide nanoparticles) nanoscale delivery systems have demonstrated capability to overcome some of these physiological barriers during transportation and metabolism stages. To better deal with those barriers, polymer-lipid complex nanoparticles are being explored and developed to merge the beneficial features and overcome the respective shortcomings of lipid-based and polymer-based nanoparticles. This paper aims to provide an overview of the various preparation strategies and supramolecular interactions of orally administered polymer-lipid complex nanoparticles by reviewing recent studies. Two types of polymer-lipid complex nanoparticles have been developed, i.e., lipid core with polymer shell nanoparticles and polymer core with lipid shell nanoparticles (lipid-polymer hybrid nanoparticles). Besides, both natural and synthetic polymers used for fabrication are discussed and their advantages and disadvantages are highlighted. Further research work is needed to optimize the fabrication and scaling up processes, so that these versatile polymer-lipid complex nanoparticles could have a significant impact on the oral delivery of nutrient/drug.
文摘This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.
