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Photosensitive liposome with encapsulated water-soluble medicament

A water-soluble, photosensitive lipid technology, used in liposome delivery, drug combination, anti-tumor drugs, etc.

Active Publication Date: 2013-09-11
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In practical applications, thermosensitive liposomes loaded with water-soluble drugs only rely on local high temperature, which does not allow the encapsulated drugs to be released quickly and in large quantities.
The encapsulated drug is released too slowly, which directly leads to a low local drug concentration in the tumor

Method used

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  • Photosensitive liposome with encapsulated water-soluble medicament
  • Photosensitive liposome with encapsulated water-soluble medicament
  • Photosensitive liposome with encapsulated water-soluble medicament

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Composition of photosensitive liposomes:

[0054] Doxorubicin Hydrochloride (DOX·HCI) 2.76mg

[0055] Dipalmitoylphosphatidylcholine (DPPC ） 31.64mg

[0056] Hydrogenated Soy Lecithin (HSPC) 11.42mg

[0057] Cholesterol 5.0mg

[0058] Polyethylene glycol phospholipids (DSPE-PEG 2000 ) 7.2mg

[0059] OMP-modified hollow gold nanoparticles (OMP-HAuNS) 1.0mg (~2.5×10 12 particles)

[0060] Prescription amounts of DPPC, HSPC, Cholesterol, DSPE-PEG 2000 and OMP-HAuNS (HAuNS : OMP = 1:0.0279 w / mol), placed in an eggplant-shaped bottle, dissolved in an organic solvent (chloroform:dichloromethane = 1:1 v / v), and vacuum reduced in a water bath at 45°C. Rotary evaporation was carried out overnight, and a thin film was formed on the bottle wall. Add ammonium sulfate solution with pH = 5.4 into the eggplant-shaped bottle, and hydrate in a water bath at 60°C for 1 hour, the film falls off and dissolves to form a multilayered liposome solution. Sonica...

Embodiment 2

[0078] Composition of photosensitive liposomes:

[0079] Doxorubicin Hydrochloride (DOX·HCI) 2.76mg

[0080] Dipalmitoylphosphatidylcholine (DPPC) 31.64mg

[0081] Hydrogenated Soy Lecithin (HSPC) 11.42mg

[0082] Cholesterol 5.0mg

[0083] Polyethylene glycol phospholipids (DSPE-PEG 2000 ) 7.2mg

[0084] Hollow gold nanoparticles (HAuNS ) 1.0mg (~2.5×10 12 particles)

[0085] Prescription amounts of DPPC, HSPC, Cholesterol, DSPE-PEG 2000 and HAuNS were placed in an eggplant-shaped bottle, dissolved in an organic solvent (chloroform: dichloromethane = 1:1 v / v), and evaporated overnight in a water bath at 45°C under vacuum under reduced pressure to form a thin film on the bottle wall. Add ammonium sulfate solution with pH = 5.4 into the eggplant-shaped bottle, and hydrate in a water bath at 60°C for 1 hour, the film falls off and dissolves to form a multilayered liposome solution. Sonicate the above solution to the desired particle size using probe sonication. The resu...

Embodiment 3

[0087] Composition of photosensitive liposomes:

[0088] Doxorubicin Hydrochloride (DOX·HCI) 2.76mg

[0089] Dipalmitoylphosphatidylcholine (DPPC) 31.64mg

[0090] Hydrogenated Soy Lecithin (HSPC) 11.42mg

[0091] Cholesterol 5.0mg

[0092] Polyethylene glycol phospholipids (DSPE-PEG 2000 ) 7.2mg

[0093] Polyethylene glycol phospholipid modified hollow gold nanoparticles (DSPE-PEG 2000 - HAuNS) 1.0mg (~2.5×10 12 particles)

[0094] Prescription amounts of DPPC, HSPC, Cholesterol, DSPE-PEG 2000 and DSPE-PEG 2000 -HAuNS (HAuNS : DSPE-PEG 2000 -SH=1:0.0279 w / mol), placed in an eggplant-shaped bottle, dissolved in an organic solvent (chloroform:dichloromethane=1:1 v / v), evaporated in a water bath at 45°C under reduced pressure overnight, and the bottle The walls form a thin film. Add ammonium sulfate solution with pH = 5.4 into the eggplant-shaped bottle, and hydrate in a water bath at 60°C for 1 hour, the film falls off and dissolves to form a multilayered liposome so...

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Abstract

The invention provides a photosensitive liposome with encapsulated water-soluble medicament, which is composed of temperature-sensitive phospholipid, cholesterol and long circulation material and hollow gold nanoparticle, wherein, the hollow gold nanoparticle has a characteristic absorption peak at the near infrared zone with the wavelength of 700-900 nm, and the particle size distribution of the hollow gold nanoparticle is in the range of 20-100 nm. According to the invention, a brand new photosensitive liposome is composed by wrapping water-soluble medicament and hollow gold nanoparticle with temperature-sensitive liposome. Under the extraneous near infrared light, the wrapped hollow gold nanoparticle generates a photo-thermal treatment effect, simultaneously, the photo-thermal effect controls a rapid site-specific delivery of medicament in a large amount from the photosensitive liposome, thereby blood vessels in the tumour part can be damaged or the tumor cells can be killed effectively with a chemical treatment effect of the medicamen. The drug loaded liposome of the present invention realizes synchronous photo-thermal and medicament molecule treatment effect, and the treatment effect of disease such as tumour is substantially improved, and the invention has clinic applicability and real treatment meaning.

Description

[0001] technical field [0002] The invention relates to a novel photosensitive liposome drug delivery system carrying water-soluble drugs, a preparation method of the photosensitive liposome and its application in anti-tumor combined with external near-infrared light. Background technique [0003] Since Yatvin first published the temperature-sensitive effect of dipalmitoylphosphatidylcholine (DPPC) liposomes on Science in 1978 and the possibility of using it as a heat-sensitive targeting drug carrier, thermosensitive liposomes have been the subject of liposomes. It is a hotspot in the field of plastid targeting research, and it has been combined with tumor hyperthermia from the beginning. Thermosensitive liposomes are usually prepared from thermosensitive materials such as DPPC whose phase transition temperature (41°C) is slightly higher than normal temperature. Above the phase transition temperature, the liposome phospholipid bilayer changes from a densely arranged colloi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K45/00A61K41/00A61P35/00
Inventor 游剑张培尊胡富强杜永忠袁弘
Owner ZHEJIANG UNIV
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