Direct comparison of two albumin-based paclitaxel-loaded nanoparticle formulations: is the crosslinked version more advantageous?
Nanoparticles using albumin as particle matrix have entered the mainstream of drug delivery. It was reported that non-crosslinked albumin nanoparticles were unstable in circulation and could deliver drugs into tumor through gp60/SPARC pathway; in contrast, the delivery of drugs with stable nanoparticles was dependent on enhanced permeability and retention effect. Thus, it is questionable which kind of nanoparticles was more advantageous. Two versions of albumin-bound paclitaxel nanoparticles were prepared. In vitro, the non-crosslinked particles could rapidly disintegrate and the crosslinked was stable. The pharmacokinetics of both formulations was different especially at early time and the non-crosslinked particles were cleared rapidly. After non-crosslinked particle treatment paclitaxel had a tendency to accumulate into heart and kidney and following therapy with the crosslinked particles, paclitaxel was liable to be delivered into lung, spleen and liver. The delivery efficiency of paclitaxel into tumor following the non-crosslinked particle treatment was greater than that of the crosslinked (p<0.05), thus resulting in a considerably improved antineoplastic activity. Moreover, the non-crosslinked formulation was only slightly more toxic. It was concluded that the non-crosslinked formulation was more advantageous for the delivery of paclitaxel and our conclusion might be generalized to other lipophilic drugs delivered with albumin nanoparticles.
School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China. Electronic address: lcllib@hotmail.com.
Chunlei
C
Li
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China.
Yanhui
Y
Li
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China.
Yuqing
Y
Gao
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China.
Na
N
Wei
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China.
Xi
X
Zhao
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
Caixia
C
Wang
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
Yongfeng
Y
Li
CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
Xian
X
Xiu
School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China. Electronic address: cjxlib@hotmail.com.
Jingxia
J
Cui
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010539:Permeability; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D017239:Paclitaxel
Albumin; Efficacy; Nanoparticles; Paclitaxel; Pharmacokinetics; Stability