Folate-polyethyleneimine functionalized mesoporous carbon nanoparticles for enhancing oral bioavailability of paclitaxel.
Polymer-functionalized carbon nanoparticles hold great promise for their use in enhancing the oral absorption of drugs with poor oral bioavailability. And since the abundant expression of folate receptors in intestinal tract, folic acid (FA) modified uniform mesoporous carbon spheres (UMCS) was used to improve oral absorption of paclitaxel, a chemotherapeutic drug with poor oral bioavailability. In this research, folate-polyethyleneimine (FA-PEI) was grafted onto acid-treated uniform mesoporous carbon spheres through one-step electrostatic attraction. PTX was loaded into mesopores of nanoparticles through solvent evaporation, present as amorphous. The release of PTX from the FA-PEI-UMCS nanoparticles exhibited an initial rapid release, followed by a sustained release. And release rate could be regulated by changing amount of FA-PEI complex on the UMCS. The uptake of PTX-encapsulated nanoparticles was studied exploiting Caco-2 cells as an in vitro model. The results of confocal microscopy and flow cytometry demonstrated that folate functionalization enhanced internalization of nanoparticles by the cells. Moreover, PTX loaded in FA-PEI-UMCS nanoparticles resulted in a 5.37-fold increase in apparent permeability (Papp) across Caco-2 cell monolayers compared to Taxol(®). And the in vivo results showed that FA-PEI-UMCS nanoparticles did not only improve the oral bioavailability of PTX, but also decrease the gastrointestinal toxicity of PTX. In conclusion, the FA-PEI-UMCS nanoparticles might be a potentially applicable system to improve oral absorption of drugs with poor oral bioavailability.
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Long
L
Wan
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Xiaofan
X
Wang
Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
Wenquan
W
Zhu
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Chen
C
Zhang
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Aihua
A
Song
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Changshan
C
Sun
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Tongying
T
Jiang
School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China. Electronic address: silingwang@syphu.edu.cn.
Siling
S
Wang
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002244:Carbon / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley
D002244:Carbon; D011094:Polyethyleneimine; D005492:Folic Acid; D017239:Paclitaxel
Electrostatic attraction; Mesoporous carbon; Oral bioavailability; Polyethyleneimine