Denatured protein-coated docetaxel nanoparticles: Alterable drug state and cytosolic delivery.
Many lead compounds have a low solubility in water, which substantially hinders their clinical application. Nanosuspensions have been considered a promising strategy for the delivery of water-insoluble drugs. Here, denatured soy protein isolate (SPI)-coated docetaxel nanosuspensions (DTX-NS) were developed using an anti-solvent precipitation-ultrasonication method to improve the water-solubility of DTX, thus improving its intracellular delivery. DTX-NS, with a diameter of 150-250nm and drug-loading up to 18.18%, were successfully prepared by coating drug particles with SPI. Interestingly, the drug state of DTX-NS was alterable. Amorphous drug nanoparticles were obtained at low drug-loading, whereas at a high drug-loading, the DTX-NS drug was mainly present in the crystalline state. Moreover, DTX-NS could be internalized at high levels by cancer cells and enter the cytosol by lysosomal escape, enhancing cell cytotoxicity and apoptosis compared with free DTX. Taken together, denatured SPI has a strong stabilization effect on nanosuspensions, and the drug state in SPI-coated nanosuspensions is alterable by changing the drug-loading. Moreover, DTX-NS could achieve cytosolic delivery, generating enhanced cell cytotoxicity against cancer cells.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Li
L
Zhang
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Qingqing
Q
Xiao
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Yiran
Y
Wang
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Chenshuang
C
Zhang
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: weihe@cpu.edu.cn.
Wei
W
He
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lifangyin_@163.com.
Lifang
L
Yin
D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011489:Protein Denaturation; D044967:Serum / Q000737:chemistry; D030262:Soybean Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D016898:Interferon-alpha; D030262:Soybean Proteins; D043823:Taxoids; D000077143:Docetaxel; D018664:Interleukin-12
4′,6-Diamidino-2-phenylindole (PubChem CID: 160166); 5-Diphenyltetrazolium bromide (PubChem CID: 64965); Cellular uptake; Chlorpromazine (PubChem CID: 2726); Cytosolic delivery; Dimethyl sulfoxide (PubChem CID: 679); Docetaxel; Docetaxel (PubChem CID: 148124); Fluorescein isothiocyanate (PubChem CID: 18730); Nanosuspensions; Rhodamine B isothiocyanate (PubChem CID: 6455488); Soy protein isolate; Trehalose (PubChem CID: 7427); Tween-80 (PubChem CID: 5281955); nystatin (PubChem CID: 6433272)