CN108743524B

CN108743524B - Application of liposome in lubricating liquid, lubricating liquid and preparation method thereof

Info

Publication number: CN108743524B
Application number: CN201810600840.XA
Authority: CN
Inventors: 张洪玉; 孙涛
Original assignee: Tsinghua University
Current assignee: Tsinghua University
Priority date: 2018-06-12
Filing date: 2018-06-12
Publication date: 2020-10-30
Anticipated expiration: 2038-06-12
Also published as: CN108743524A

Abstract

The invention discloses a lubricating liquid, which comprises an aqueous solvent and liposome dispersed in the aqueous solvent, wherein the liposome comprises a shell and nanoparticles wrapped in the shell, and the shell is formed by at least one phospholipid bilayer. The invention also discloses an application of the liposome in lubricating fluid. The invention also discloses a preparation method of the lubricating liquid and application of the liposome in the lubricating liquid.

Description

Application of liposome in lubricating liquid, lubricating liquid and preparation method thereof

Technical Field

The invention relates to the field of liposome, in particular to application of liposome in lubricating liquid, the lubricating liquid and a preparation method of the lubricating liquid.

Background

Liposomes are a formulation of ultramicro-spherical carriers formed by phospholipid bilayers, which are typical representatives of nano drug-carrying systems. When amphiphilic molecules such as phospholipids are dispersed in an aqueous phase, the hydrophobic tails of the molecules are brought together and the hydrophilic heads are exposed to the aqueous phase, forming closed vesicles with a bilayer structure. A plurality of drugs with different polarities can be wrapped in the vesicle inner water phase and the bilayer membrane. In addition, the liposome has good biocompatibility and can be metabolized normally, so that the liposome has great development potential as a drug carrier.

The liposome has good lubricating property, but because the liposome is easy to break when bearing pressure, the liposome has obvious defects in the aspects of bearing capacity, stability and the like when being used as a lubricant.

Disclosure of Invention

In view of the above, it is necessary to provide a use of liposome in a lubricating fluid, a lubricating fluid and a method for preparing a lubricating fluid, in order to solve the problem that the pressure-bearing capacity of liposome used as a lubricant is poor.

A lubricating fluid comprising an aqueous solvent and liposomes dispersed in the aqueous solvent, the liposomes comprising a shell and nanoparticles entrapped in the shell, the shell being formed from at least one phospholipid bilayer.

In one embodiment, the concentration of the liposomes in the lubricating liquid is between 1mg/mL and 100 mg/mL.

In one embodiment, the outer diameter of the shell is 100nm to 400 nm.

In one embodiment, the nanoparticle comprises one or more of mesoporous silicon, nanogel, and a nano-polymer material.

In one embodiment, the nanoparticles have a diameter of 50nm to 350 nm.

In one embodiment, the diameter of the nanoparticle is equal to the inner diameter of the shell.

In one embodiment, the shell is composed of a plurality of phospholipid bilayers arranged in a stacked manner.

In one embodiment, the phospholipid bilayer is also interspersed with stabilizers, which are lipid molecules with long-chain hydrophobic groups and do not contain phosphate groups.

Use of a liposome in a lubricating fluid, the liposome comprising a shell and a nanoparticle encapsulated in the shell, the shell being formed of at least one phospholipid bilayer.

In one embodiment, the lubricating liquid is formed by dispersing the liposomes in an aqueous solvent, wherein the concentration of the liposomes in the lubricating liquid is from 1mg/mL to 100 mg/mL.

The preparation method of the lubricating liquid comprises the following steps:

s1, providing a phospholipid molecule solution, wherein the phospholipid molecule solution comprises a solvent and phospholipid molecules dissolved in the solvent;

s2, adding the phospholipid molecule solution into a container, then removing the solvent in the phospholipid molecule solution, and forming a phospholipid bilayer film at the bottom of the container;

s3, dispersing nanoparticles on the surface of the phospholipid bilayer film, and adding water on the surface of the phospholipid bilayer film; and

s4, breaking the phospholipid bilayer membrane and hydrating to obtain a first dispersion liquid containing a first liposome, wherein the first liposome comprises the shell and the nano-particles, and the shell is composed of one layer of the phospholipid bilayer.

In one embodiment, after the step S4, the method further includes the following steps:

repeating the steps S1 and S2;

dispersing the first liposome on the surface of the phospholipid bilayer membrane, and adding water on the surface of the phospholipid bilayer membrane;

and (c) breaking and hydrating the phospholipid bilayer membrane to obtain a second dispersion comprising a second liposome, wherein the second liposome comprises the shell and the nanoparticles, and the shell is composed of at least two phospholipid bilayers.

In one embodiment, the phospholipid bilayer membrane after adding water is sonicated to rupture the phospholipid bilayer membrane.

In one embodiment, the temperature of the hydration is 50-70 ℃, and the hydration time is 0.5-1.5 h.

In one embodiment, the first dispersion or the second dispersion is used as the lubricating liquid.

In one embodiment, the method further comprises the following steps:

centrifuging the first dispersion liquid or the second dispersion liquid to obtain the first liposome or the second liposome;

re-dispersing the first liposome or the second liposome in the aqueous solvent to obtain the lubricating fluid.

In one embodiment, the rotation speed of the centrifugal separation is 6000 r/min-10000 r/min.

According to the lubricating liquid provided by the invention, the liposome internally supported with the nanoparticles is used as the lubricant, on one hand, the phospholipid bilayer shell structure enables the lubricating liquid to effectively improve the lubricating condition of a joint contact area, so that the joint abrasion can be reduced, and the joint repair is promoted, on the other hand, the nanoparticles are supported in the shell, so that the liposome can not break when bearing larger pressure while the lubricating property of the liposome is maintained, the lubricating liquid has better stability and bearing capacity, and the liposome cannot break due to the pressure borne by the friction surface of the joint, so that the lubricating liquid has better lubricating durability, and when the lubricating liquid is used for a human body, the injection frequency can be reduced, and the pain of a patient can be relieved. In addition, the liposome has components similar to cell membranes, and has good biocompatibility when used as joint lubricating fluid.

Drawings

FIG. 1 is a schematic structural diagram of a liposome according to one embodiment of the present invention;

FIG. 2 is a schematic structural diagram of a liposome according to another embodiment of the present invention;

FIG. 3 is a schematic flow chart of a method of preparing a lubricating fluid according to an embodiment of the present invention;

FIG. 4 is a graph comparing the friction coefficient curves of mesoporous silica, unloaded Distearoylphosphatidylcholine (DPSC) liposomes, first liposomes, and second liposomes as lubricious additives under gradient loading in accordance with examples of the invention;

FIG. 5 is a graph comparing the coefficient of friction of the first liposomal lubricating fluid and the second liposomal lubricating fluid at different frequencies according to the example of the invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more clearly understood, the following examples, with reference to the accompanying drawings, further illustrate the application of the liposome in the lubricating fluid, the lubricating fluid and the preparation method of the lubricating fluid. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Referring to fig. 1, the embodiment of the present invention provides a liposome 11, where the liposome 11 includes a shell and a nanoparticle 112 encapsulated in the shell, and the shell is composed of at least one phospholipid bilayer 111.

The application provides a liposome, when being applied to lubricating liquid, the 111 shell structures of phospholipid bilayer make lubricating liquid can effectively improve the lubricated condition of joint contact zone, can reduce joint wear when being applied to osteoarthritis treatment, promotes joint restoration. The nano particles 112 are supported in the shell, so that the liposome 11 can not break when bearing large pressure while the lubricity of the liposome 11 is maintained, the lubricating liquid has better stability and bearing capacity, the liposome 11 cannot break due to the pressure borne by the joint friction surface, the lubricating liquid has better lubricating durability, and the injection frequency can be reduced and the pain of a patient can be relieved when the lubricating liquid is used for a human body. In addition, the liposome 11 has a composition similar to that of a cell membrane, and is excellent in biocompatibility when used as a joint lubricating fluid.

The phospholipid bilayer 111 is composed of phospholipid molecules, which are amphiphilic lipids containing phosphoric acid and are the main constituents of biological membranes. Preferably, the phospholipid molecule has a hydrophobic group composed of a long-chain alkyl group at one end and a hydrophilic group composed of a phosphate group at the other end. The phospholipid molecules may include one or more of phosphoglycerides and sphingomyelin. Wherein the phosphoglycerol may include one or more of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, Phosphatidylglycerol (PG), and glycerophosphatidic acid. The phospholipid molecules may be used alone or in combination of a plurality of them. The phospholipid molecule is preferably distearoyl phosphatidylcholine, the end group of the distearoyl phosphatidylcholine is phosphatidylcholine, the hydrophilicity is stronger, and the performance of the liposome forming a shell-core structure is better. Preferably, the outer diameter of the shell may be 100nm to 400nm, and the liposome 11 in this range has both good lubricity and pressure-bearing capability.

In one embodiment, the liposomes 11 further comprise a stabilizer that can be interpenetrated within the phospholipid bilayer 111. The stabilizer may include a lipid molecule having a long-chain hydrophobic group and not containing a phosphate group, which may be bound to the phospholipid molecule through molecular interaction, enhancing the strength of the shell structure of the phospholipid bilayer 111. The stabilizer is preferably cholesterol. In one embodiment, the molar ratio of the phospholipid molecules and the stabilizer in the liposome may be (50-100): (0-50), preferably (50-70): (30-50), and in the molar ratio range, the phospholipid molecules have better film-forming property, and the formed liposome structure is more stable.

The kind and the chargeability of the nanoparticles 112 are not limited, and may be positively charged, negatively charged, or uncharged. In one embodiment, the nanoparticles 112 may include one or more of mesoporous silicon, nanogels, and nano-polymer materials. The nanoparticles 112 are preferably hard particles, such as mesoporous silicon, to provide better support for the shell. The diameter of the nanoparticles 112 may be 50nm to 350nm, and the nanoparticles 112 in this range may support the shell well without affecting the lubricating properties of the liposome. Preferably, only one nanoparticle 112 is encapsulated within the shell, making the structure of the liposome 11 more stable. The diameter of the nanoparticles 112 and the inner diameter of the shell may be substantially equal, enhancing the supporting effect of the nanoparticles 112.

Preferably, the liposome 11 further comprises a drug encapsulated in the shell, wherein the drug can be a drug for treating arthritis, and the drug can be independently dispersed in the shell or bonded on the surface of the nanoparticle 112. When the liposome 11 carries medicine, the phospholipid bilayer 111 is used as a slow release layer, so that a better medicine slow release effect is achieved, the medicine release period is longer after medicine carrying, and the administration interval can be effectively increased.

Referring to fig. 2, preferably, the shell is composed of a plurality of phospholipid bilayers 111 arranged in a stacked manner. The liposome formed by the nano-particles 112 wrapped by the multi-layer phospholipid bilayers 111 has better lubricating effect. Preferably, the number of the phospholipid bilayers can be 2 to 4, so that the formed lubricating liquid has good lubricating property and good pressure bearing performance.

The embodiment of the application also provides an application of the liposome 11 in lubricating fluid. The liposomes 11 may be dispersed in an aqueous solvent to provide the lubricating fluid.

The embodiment of the present application also provides a lubricating liquid, which comprises an aqueous solvent and the liposome 11 dispersed in the aqueous solvent. The lubricating fluid may be a joint lubricating fluid.

In one embodiment, the concentration of the liposomes 11 in the lubricating fluid can be from 1mg/mL to 100mg/mL, preferably from 1mg/mL to 20mg/mL, more preferably from 5mg/mL to 15 mg/mL. Within the range, the lubricating liquid has proper fluidity and good lubricating performance, and can not generate adverse effect on human body when being used as joint lubricating liquid.

The lubricating fluid of the present application may be administered by intra-articular injection, arthroscopic administration, surgical administration, or may be administered to the diseased joint by any form of administration that is instilled into the synovial membrane of the joint or onto the articular cartilage.

Referring to fig. 3, an embodiment of the present invention provides a method for preparing the lubricating fluid, including the following steps:

s3, dispersing the nanoparticles 112 on the surface of the phospholipid bilayer film, and adding water on the surface of the phospholipid bilayer film;

s4, breaking the phospholipid bilayer membrane and hydrating it, resulting in a first dispersion comprising first liposomes comprising the capsid and the nanoparticles 112, the capsid consisting of one layer of the phospholipid bilayer 111.

In step S1, the solvent is used to disperse the phospholipid molecules and mix the phospholipid molecules uniformly. The solvent in the phospholipid molecule solution can be an organic solvent, such as chloroform, and preferably is a mixed solution of chloroform and methanol, and the molar ratio of chloroform to methanol in the mixed solution is preferably 85: 15.

The phospholipid molecule solution may further comprise the stabilizer. The stabilizer may also be dissolved in the solvent. Preferably, the concentration of the phospholipid molecules in the phospholipid molecule solution can be 2 mg/mL-6 mg/mL, and within the concentration range, the phospholipid molecules have better film forming effect and are easier to form a monolayer phospholipid bilayer film.

In the step S2, the solvent may be removed by natural air drying, heat drying or rotary evaporation. The container may be a flat bottom container, for example a pear-shaped container, which may be used in direct connection with a rotary evaporator. During the process of removing the solvent, the hydrophobic groups of the phospholipid molecules aggregate and the hydrophilic groups are exposed to the outside to form a phospholipid bilayer film. The temperature for removing the solvent can be 50-70 ℃, and the film forming effect of the phospholipid molecules is better in the temperature range. Preferably, the temperature of the solvent removal is 60 ℃.

In step S3, in one embodiment, the nanoparticles 112 can be directly dispersed on the surface of the phospholipid bilayer membrane. In another embodiment, a dispersion of nanoparticles 112 can also be provided, and the dispersion of nanoparticles 112 can be added to the surface of the phospholipid bilayer membrane in a manner that facilitates uniform dispersion of nanoparticles 112 on the phospholipid bilayer 111 membrane. The dispersion of the nanoparticles 112 on the phospholipid bilayer membrane and the addition of the water may be performed in two steps, or may be added at a time. In one embodiment, the nanoparticles 112 are dispersed in an aqueous solvent to obtain a dispersion of the nanoparticles 112, and the additional step of adding water can be omitted after the dispersion of the nanoparticles is added to the surface of the phospholipid bilayer membrane. It is to be understood that additional water may be added if the amount of water solvent in the nanoparticle dispersion is small.

In one embodiment, the step S3 may further include a step of dispersing the drug on the surface of the phospholipid bilayer membrane, so that the drug and the nanoparticles 112 can be simultaneously encapsulated inside the phospholipid bilayer 111 in a subsequent step to form a drug-loaded liposome. The addition amount of the nanoparticles 112 and the drug can be selected according to actual needs.

In the step S4, by breaking the complete phospholipid bilayer membrane into dispersed membranes, the hydrophilic ends on both sides of the broken membrane gather into water, and wrap the nanoparticles 112 at the same time, so as to form a structure in which the phospholipid bilayer shell wraps the nanoparticles 112, thereby obtaining the first liposome.

In one embodiment, the phospholipid bilayer membrane is disrupted by sonicating the phospholipid bilayer membrane after adding water. The hydration temperature may be 50-70 deg.c, and the film broken in the temperature range may be gathered into closed liposome easily. The hydration time may be 0.5h to 1.5 h.

The steps S1 to S4 can be repeated for a plurality of times in a circulating way, and the liposome prepared in each time can be used as the nano-particle in the next repeated step, so that the structure of the multi-layer phospholipid bilayer shell-wrapped nano-particle can be obtained.

In an embodiment, after the step S4, the method further includes the following steps:

s5, repeating the step S1 and the step S2;

s6, dispersing the first liposome on the surface of the phospholipid bilayer membrane, and adding water on the surface of the phospholipid bilayer membrane; and

s7, disrupting and hydrating the phospholipid bilayer membrane to obtain a second dispersion comprising a second liposome comprising the capsid and the nanoparticle 112, the capsid being composed of at least two layers of the phospholipid bilayer 111.

The step S6 is substantially the same as the step S3 except that the first liposome is used in place of the nanoparticle 112. In one embodiment, the first dispersion can be applied directly to the surface of the membrane of the phospholipid bilayer 111. In another embodiment, the first dispersion may be centrifuged to obtain first liposomes, the first liposomes are dispersed on the surface of the phospholipid bilayer 111 film, and then water is added on the surface of the phospholipid bilayer film. By centrifugation, the water solvent is removed and at the same time, the empty liposomes that do not encapsulate the nanoparticles 112 can be removed. The rotation speed of the centrifugation can be 6000r/min to 10000r/min, such as 8000r/min, and the empty liposomes which are not coated with the nano particles 112 can be removed in the rotation speed range, and meanwhile, the first liposome can not be broken in the centrifugation process.

In the step S7, the first liposome is used as a core, and a new phospholipid bilayer 111 is coated on the surface of the first liposome to obtain a second liposome in which a nanoparticle 112 is coated with a multi-phospholipid bilayer 111, and the lubricating ability of the liposome is further improved by coating multiple layers of stacked phospholipid bilayers 111 on the surface of the nanoparticle 112. A second liposome

In an embodiment, the first dispersion or the second dispersion may be used directly as the lubricating liquid.

In another embodiment, the size of the first liposome or the second liposome can also be calibrated to obtain liposomes of more uniform size. The step of calibrating the size of the first liposome or the second liposome comprises:

passing the first dispersion or the second dispersion through a filter membrane to calibrate the size of the first liposome or the second liposome. Specifically, the first dispersion liquid or the second dispersion liquid may be injected into a liposome extruder, a filter having a certain pore size is provided in the liposome extruder, and the first dispersion liquid or the second dispersion liquid is extruded inside the liposome extruder to pass through the filter having a certain pore size, so that the first liposome or the second liposome is calibrated in size to obtain liposomes having uniform particle sizes. The pore size of the filter membrane can be 100 nm-400 nm.

In another embodiment, water may be further added to the first dispersion or the second dispersion to adjust the concentration of the first liposome or the second liposome in the lubricating liquid.

In another embodiment, the first liposome or the second liposome can be separated from the first dispersion or the second dispersion and then redispersed in the aqueous solvent to form the lubricating fluid. Centrifugation can be used to separate the first liposome or the second liposome. The empty liposomes in the first dispersion or the second dispersion can be removed together by adjusting the rotational speed of the centrifugation. Preferably, the rotational speed of the centrifugation may be 6000r/min to 10000r/min, such as 8000r/min, within which the empty liposomes not encapsulating the nanoparticles 112 can be removed without causing rupture of the first or second liposomes during the centrifugation.

EXAMPLE 1 preparation of the first liposomes

(1) Distearoylphosphatidylcholine (DPSC)7.9mg and cholesterol 1.97mg were put into a 50mL pear-shaped flask, and 2mL of a chloroform-methanol mixture (methanol: chloroform: 85:15) was added to completely dissolve the mixture.

(2) The pear-shaped flask was mounted on a rotary evaporator and the solvent was spun off at 60 ℃ to form a uniform thin film of phospholipid bilayer 111 at the bottom of the pear-shaped flask.

(3) 10mg of mesoporous silicon is taken to be ultrasonically dispersed in 1mL of water, and 0.5mL of mesoporous silicon dispersion liquid with the particle size of 100nm is taken to be uniformly dripped on the surface of the phosphophospholipid bilayer 111 film in a pear-shaped bottle.

(4) Sucking 2mL of water, adding the water into a pear-shaped bottle, performing ultrasonic treatment to break and separate all the phospholipid bilayer 111 films, putting the pear-shaped bottle into a water bath, and performing heat preservation at 60 ℃ for 1 hour to obtain a first liposome dispersion liquid.

(5) The first liposome dispersion was aspirated by 1mL, and the first liposome size was calibrated by extruding the first liposome dispersion on a liposome extruder 11 times through 300nm carbon membranes, respectively.

EXAMPLE 2 preparation of the second liposome

This example differs from example 1 in that the mesoporous silicon of example 1 is replaced with a first liposome.

(3) 0.5mL of the first liposome dispersion obtained in example 1 was uniformly dropped on the surface of a new phospholipid bilayer 111 film in a pear-shaped flask.

(4) And (3) sucking 2mL of water, adding the water into a pear-shaped bottle, performing ultrasonic treatment to break and separate all phospholipid bilayer films, putting the pear-shaped bottle into a water bath, and preserving heat at 60 ℃ for 1 hour to obtain a second liposome dispersion liquid.

(5) The second liposome dispersion was aspirated by 1mL, and the second liposome size was calibrated by extruding the second liposome dispersion on a liposome extruder 11 times through 400nm carbon membranes, respectively.

Comparative example 1 preparation of No-load DPSC liposomes

(1) Into a 50mL pear-shaped flask were added 7.9mg of distearoylphosphatidylcholine and 1.97mg of cholesterol, and 2mL of a chloroform-methanol mixture (methanol: chloroform: 85:15) was added to completely dissolve the distearoylphosphatidylcholine and the cholesterol.

(2) The pear-shaped bottle was mounted on a rotary evaporator and the solvent was spun off at 60 ℃ to form a uniform phospholipid bilayer film at the bottom of the pear-shaped bottle.

(3) And (3) sucking 2mL of water, adding the water into a pear-shaped bottle, performing ultrasonic treatment to break and separate all phospholipid bilayer films, putting the pear-shaped bottle into a water bath, and preserving heat at 60 ℃ for 1 hour to obtain the no-load DPSC liposome dispersion liquid.

(4) 1mL of the unloaded DPSC liposome dispersion liquid was sucked, and the loaded DPSC liposome was extruded 11 times through 300nm carbon lipid membranes on a liposome extruder, respectively, to calibrate the size of the unloaded DPSC liposome.

Coefficient of friction test

The friction coefficient detection is carried out on a UMT-3 friction wear testing machine, the stroke is 4mm, the frequency is 1Hz, 5Hz and 10Hz respectively, and the experimental time is 30 min. The titanium alloy sheet (Ti6Al4V type) was the lower sample, the polyethylene ball (PE) was the upper sample, the loading forces were 1N, 2N and 4N, and the contact stresses were 26MPa, 32MPa and 41MPa, respectively.

The mesoporous silicon nanoparticles, the unloaded DPSC liposome of comparative example 1, the first liposome of example 1, and the second liposome of example 2 were prepared into 10mg/mL lubricating fluids using water as a solvent, titanium alloy-PE was added to the lubricating fluids as friction pairs, and the change of friction coefficient of the lubricating fluids under gradient loads of 1N, 2N, and 4N was measured at a frequency of 3Hz, and the results of the measurement are shown in fig. 4.

As can be seen from fig. 4, the friction coefficient of the mesoporous silicon lubricating fluid is much larger than that of the unloaded DPSC liposome, the first liposome and the second liposome lubricating fluid with the same concentration, which indicates that the mesoporous silicon as an additive does not have a lubricating function, but rather increases the friction coefficient. In these few samples, the friction coefficient of the unloaded DPSC liposomal lubricating fluid was minimal, and an ultra-low friction coefficient close to 0.02 was achieved at 1N load, with a significant increase in friction coefficient of the unloaded DPSC liposomal lubricating fluid as the load increased, and with a substantial amount of rupture of the unloaded DPSC liposomes as the load increased to 4N.

The friction coefficient of the first liposome lubricating fluid and the second liposome lubricating fluid is far lower than that of mesoporous silicon, although the friction coefficient at 1N is higher than that of the no-load liposome lubricating fluid, the friction coefficient gradually approaches that of the no-load liposome lubricating fluid along with the increase of load, and when the load reaches 4N, the first liposome and the second liposome are still not cracked. Therefore, the first liposome and the second liposome still have good lubricating property under high load, and show good bearing capacity.

The first liposome and the second liposome were prepared into lubricating fluids of 2mg/mL, 5mg/mL and 10mg/mL, respectively, and the friction coefficients were determined by the same method as described above, and the results are shown in table 1, where it can be seen that the friction coefficient of the lubricating fluid becomes smaller and the lubricating performance becomes better as the concentration of the liposome increases, and the friction coefficient of the lubricating fluid of the second liposome is smaller than that of the first liposome having the same concentration, indicating that the lubricating fluid formed by the second liposome has better lubricating performance and pressure-bearing capacity than that of the lubricating fluid of the first liposome.

TABLE 1 comparison of Friction coefficients for different concentrations of first and second liposomal lubricating fluids

The friction coefficient of the first liposome lubricating fluid and the second liposome lubricating fluid at a concentration of 10mg/mL was measured at different reciprocation frequencies (1Hz, 5Hz, 10Hz) and a load of 1N, and the results are shown in fig. 5, which shows that the friction coefficients of the first liposome lubricating fluid and the second liposome lubricating fluid decrease with increasing frequency, conforming to the characteristics of boundary lubrication.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. A lubricating fluid comprising an aqueous solvent and liposomes dispersed in the aqueous solvent, wherein the liposomes comprise a shell and nanoparticles and a drug encapsulated in the shell, the nanoparticles have a diameter equal to the inner diameter of the shell, the drug is independently dispersed in the shell or bound to the surface of the nanoparticles, the shell is formed by a plurality of phospholipid bilayer layers stacked, the nanoparticles are hard particles, and the nanoparticles are selected from mesoporous silicon.

2. The lubricating fluid of claim 1, wherein the concentration of the liposomes in the lubricating fluid is between 1mg/mL and 100 mg/mL.

3. The lubricating fluid of claim 1, wherein the housing has an outer diameter of 100nm to 400 nm.

4. The lubricating fluid according to any one of claims 1 to 3, wherein the nanoparticles have a diameter of 50nm to 350 nm.

5. The lubricating fluid of claim 4, wherein a stabilizer is further interspersed in the phospholipid bilayer, the stabilizer being a lipid molecule having a long chain hydrophobic group and not containing a phosphate group.

6. The application of the liposome in preparing the lubricating fluid is characterized in that the liposome comprises a shell and nanoparticles and a drug, wherein the nanoparticles and the drug are wrapped in the shell, the diameter of the nanoparticles is equal to the inner diameter of the shell, the drug is independently dispersed in the shell or combined on the surface of the nanoparticles, the shell is formed by a plurality of layers of phospholipid bimolecular layers which are arranged in a laminated mode, the nanoparticles are hard particles, and the nanoparticles are selected from mesoporous silicon.

7. The use of liposomes according to claim 6 for the preparation of a lubricating fluid, wherein the liposomes are dispersed in an aqueous solvent to form the lubricating fluid, and the concentration of the liposomes in the lubricating fluid is between 1mg/mL and 100 mg/mL.

8. A method of preparing the lubricating fluid of any one of claims 1-5, comprising the steps of:

s3, dispersing nanoparticles and a drug on the surface of the phospholipid bilayer film, and adding water on the surface of the phospholipid bilayer film; and

s4, breaking the phospholipid bilayer membrane and hydrating to obtain a first dispersion liquid comprising a first liposome, wherein the first liposome comprises the shell, the nanoparticles and the drug, and the shell consists of one layer of the phospholipid bilayer;

repeating the steps S1 and S2;

and (c) disrupting and hydrating the phospholipid bilayer membrane to obtain a second dispersion comprising a second liposome comprising a shell, the nanoparticle, and the drug, the shell consisting of at least two of the phospholipid bilayers.

9. The method of claim 8, wherein the phospholipid bilayer membrane after adding water is sonicated to rupture the phospholipid bilayer membrane.

10. The method for preparing the lubricating fluid according to claim 8, wherein the temperature of the hydration is 50 ℃ to 70 ℃, and the hydration time is 0.5h to 1.5 h.

11. The method for producing the lubricating liquid according to claim 8, wherein the first dispersion liquid or the second dispersion liquid is used as the lubricating liquid.

12. The method of preparing the lubricating fluid of claim 8, further comprising:

13. The method of claim 12, wherein the rotational speed of the centrifugation is 6000r/min to 10000 r/min.