CN114848644A - Nano-targeting sustained-release drug, and preparation method, device and application thereof - Google Patents
Nano-targeting sustained-release drug, and preparation method, device and application thereof Download PDFInfo
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Abstract
The invention relates to the technical field of biological medicines, and discloses a nano targeted sustained-release medicine, and a preparation method, a device and application thereof. The nano targeted slow-release medicine comprises: the surface of the drug-loaded nanomaterial carries a functional reactive group; and the chemotherapeutic drugs are loaded on the functional reaction groups on the surfaces of the drug-loaded nano materials through solution impregnation. The nano-targeted sustained-release medicament provided by the invention adopts the ultra-small magnetic iron oxide nano-ufIONP to construct a specific-performance high-efficiency medicament with targeting and sustained-release effects, solves the problems of lack of targeting, low efficiency and no sustained-release effect in clinical abdominal cavity drug delivery, and improves the clinical treatment effect of tumor and cancer medication.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a nano targeted sustained-release medicine, a preparation method and a device thereof, and application of the nano targeted sustained-release medicine in antitumor treatment.
Background
With the change of human living environment, the morbidity and mortality of tumors and cancers are increasing, and in clinical application, the cases such as tumors and cancers are treated by medicines generally, and at this time, anticancer medicines are very important.
Generally, the administration mode of anticancer drugs is to deliver drugs through the abdominal cavity, and the above-mentioned mode of intraperitoneal delivery has the problems of lack of targeting, low efficiency and no sustained release efficacy, and in addition, the anticancer drugs cannot be rapidly metabolized in vivo due to their specific structural characteristics, so that the residence time in the liver is prolonged, the safety of pharmacokinetics is reduced, and even the harm of systemic toxic and side effects caused by increasing the drug dosage to meet the drug effect and repeated use of drugs in clinic may be caused.
In summary, due to the administration mode and structural characteristics of the existing anticancer drugs, the problems of lack of targeting, low efficiency and no sustained release efficacy are caused, and even the problem of unstable administration safety is caused, which all result in the problem of low clinical treatment effect of tumor and cancer.
Disclosure of Invention
The invention mainly aims to provide a nano targeted sustained-release medicament, a preparation method, a device, equipment and application thereof, aiming at optimizing the treatment effect of clinical tumor and cancer medication.
In order to achieve the above object, the present invention provides a nano-targeted sustained release drug, which comprises:
the surface of the drug-loaded nanomaterial carries a functional reactive group;
and the chemotherapeutic drugs are loaded on the functional reaction groups on the surfaces of the drug-loaded nano materials through solution impregnation.
Preferably, the nano-targeting slow release medicine is characterized in that,
the drug-carried nano material is used as a core carrier of the chemotherapeutic drug;
the surface of the drug-loaded nanomaterial is loaded with a targeting ligand folic acid;
the targeted ligand folic acid carried on the nanometer material of the drug adsorbs irinotecan derivatives.
In order to achieve the above object, the present invention provides a method for preparing a nano-targeted sustained release drug, comprising the steps of:
constructing the drug-loaded nanomaterial based on pre-prepared ultra-small magnetic iron oxide nano ufIONP;
and (3) infusing chemotherapeutic drugs onto the drug carrying nanometer material to generate the nanometer targeted slow-release drug.
Preferably, the step of constructing the drug-loaded nanomaterial based on the pre-prepared ultra-small magnetic iron oxide nano ufIONP comprises:
filling targeted ligand folic acid serving as a prepolymer into the interlayer of a pre-prepared ultra-small magnetic iron oxide nano ufIONP laminate;
loading irinotecan derivatives serving as a pre-reactant into the interlayer of a layer of the prepared ultra-small magnetic iron oxide nano ufIONP;
polymerizing the targeted ligand folic acid with the irinotecan derivative between the lamellar layers of the ultra-small magnetic iron oxide nano ufIONP to obtain a polymeric substance of the targeted ligand folic acid;
and depositing the polymeric substance between the layers of the ultra-small magnetic iron oxide nano ufIONP to obtain the drug-loaded nano material.
Preferably, the step of infusing the chemotherapy drugs onto the drug-loaded nanomaterial to generate the nano-targeted sustained-release drug comprises:
and carrying the chemotherapeutic drug by the functional reaction group on the drug carrying nano material to generate the nano targeted slow release drug.
Preferably, after the step of infusing the chemotherapeutic drug onto the drug-loaded nanomaterial to generate the nano-targeted sustained-release drug, the method for preparing the nano-targeted sustained-release drug further comprises:
detecting the targeting property and the drug loading effect of the nano-targeted sustained-release drug by adopting a cell activity detection technology MTT;
if the targeting property and the drug loading effect of the nano-targeted sustained-release drug reach preset standards, the nano-targeted sustained-release drug can be used;
if at least one of the targeting property and the drug loading effect of the nano targeted sustained-release drug does not meet the preset standard, the nano targeted sustained-release drug is unavailable.
In order to achieve the above object, the present invention further provides an application method of a nano-targeted sustained release drug, which is characterized in that the application method of the nano-targeted sustained release drug comprises the following steps:
culturing cancer cells by simulating growth conditions in the cancer cells;
incubating the cancer cells and the nano-targeted sustained-release medicine to obtain a cancer cell animal model;
transferring the nano-targeted sustained-release drug to the cancer cell animal model by an intraperitoneal perfusion drug delivery mode to obtain performance data of the nano-targeted sustained-release drug.
In addition, in order to achieve the above object, the present invention also provides a device for preparing a nano-targeted sustained release drug, comprising:
the construction module is used for constructing the drug-loaded nanomaterial based on the prepared ultra-small magnetic iron oxide nanoparticles;
and the perfusion module is used for perfusing chemotherapeutic drugs to the drug carrying nanometer material to generate the nanometer targeted sustained-release drug.
Preferably, the building block is further configured to:
filling targeted ligand folic acid serving as a prepolymer into the interlayer of a pre-prepared ultra-small magnetic iron oxide nano ufIONP laminate;
loading irinotecan derivatives serving as a pre-reactant into the interlayer of a layer of the prepared ultra-small magnetic iron oxide nano ufIONP;
the targeted ligand folic acid is subjected to polymerization reaction with the irinotecan derivative between the lamellar substance layers of the ultra-small magnetic iron oxide nano ufIONP to obtain a polymeric substance of the targeted ligand folic acid;
and depositing the polymeric substance between the layers of the ultra-small magnetic iron oxide nano ufIONP to obtain the drug-loaded nano material.
Preferably, the perfusion module is further configured to:
and carrying the chemotherapeutic drug by the functional reaction group on the drug carrying nano material to generate the nano targeted slow release drug.
In addition, in order to achieve the above object, the present invention further provides a device for preparing a nano-targeted sustained release drug, wherein the device for preparing a nano-targeted sustained release drug comprises: the system comprises a memory, a processor and a preparation program of the nano-targeted slow-release medicine, wherein the preparation program of the nano-targeted slow-release medicine is stored on the memory and can be operated on the processor, and when the preparation program of the nano-targeted slow-release medicine is executed by the processor, the steps of the preparation method of the nano-targeted slow-release medicine are realized.
In addition, the invention also provides the application of the nano-targeted slow-release medicament in antitumor and anticancer treatment.
In the technical scheme provided by the invention, the nano targeted sustained-release medicament comprises a medicament carrying nano material and a chemotherapeutic medicament, wherein the medicament carrying nano material is taken as a core carrier and carries targeted ligand folic acid and irinotecan derivatives. The nano-targeted sustained-release medicament provided by the invention can effectively prolong the action time of the medicament on tumors, effectively penetrate to deep parts of the tumors in a targeted manner, kill tumor cells, reduce the medicament dosage and relieve normal tissue injury, and solves the problems of lack of high efficiency, targeting and sustained-release efficiency and medicament safety of the chemotherapeutic medicament in the treatment process of clinical chemotherapy.
Drawings
FIG. 1 is a schematic flow chart of a first embodiment of a method for preparing a nano-targeted sustained release drug according to the present invention;
FIG. 2 is a schematic view of a sub-process of step S10 in the first embodiment of the method for preparing a nano-targeted sustained release drug according to the present invention;
FIG. 3 is a schematic view of a sub-process of step S20 in the first embodiment of the method for preparing a nano-targeted sustained release drug according to the present invention;
fig. 4 is a schematic flowchart of step S200 in a second embodiment of the method for preparing a nano-targeted sustained release drug according to the present invention;
FIG. 5 is a schematic flow chart of a second embodiment of the method for preparing a nano-targeted sustained release drug of the present invention;
fig. 6 is a schematic flowchart of step S2020 in a third embodiment of the method for preparing a nano-targeted sustained release drug according to the present invention;
FIG. 7 is a schematic flow chart of a third embodiment of the method for preparing a nano-targeted sustained release drug of the present invention;
fig. 8 is a functional module diagram of a device for preparing a nano-targeted sustained release drug according to a first embodiment of the method for preparing a nano-targeted sustained release drug of the present invention.
The implementation, functional features and advantages of the objects of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The nano-targeted sustained release drug in some embodiments includes:
the surface of the drug-loaded nanomaterial carries a functional reactive group;
and the chemotherapeutic drugs are loaded on the functional reaction groups on the surfaces of the drug-loaded nano materials through solution impregnation.
The nano targeted slow-release medicine is characterized in that,
the drug-carried nano material is used as a core carrier of the chemotherapeutic drug;
the surface of the drug-loaded nanomaterial is loaded with a targeting ligand folic acid;
the targeted ligand folic acid carried on the nanometer material of the drug adsorbs irinotecan derivatives.
Compared with other drug carrying materials, the nano-targeted slow-release drug in the embodiment has the advantages that the nano-targeted slow-release drug has a 'superfine' structure of the drug carrying nano-material, carries more functional reaction groups on the surface of the drug carrying nano-material, has a larger drug carrying specific surface area, and is also beneficial to carrying chemotherapeutic drugs with more drug amount and linking of groups with different functions.
Furthermore, the target drug delivery effect of the nano-targeted sustained release drug is improved by constructing the multifunctional visual 'superfine' nano-carrier ultra-small magnetic iron oxide nano-ufIONP attached to the target ligand, taking the ultra-small magnetic iron oxide nano-ufIONP as a core carrier and loading the target ligand folic acid on the surface of the core carrier, and meanwhile, the irinotecan derivative SN-38 is loaded, so that the target adsorption force is improved, the concentration and depth of drug penetration are increased, and the treatment time of the drug effect is prolonged.
In particular, the 'ultra-fine' nano-carrier is constructed by adopting an original in-situ particle polymerization method and an ultra-thin coating technology, and a large number of functional reaction groups on the surface of the nano-carrier are used for folic acid targeted modification and increase of the drug-loading rate of the anti-cancer drug, so that the high-efficiency targeted delivery sustained-release drug of the ultrafine nano-carrier and the visual tracking of the curative effect of the ultrafine nano-carrier are realized, based on the successfully prepared ultrafine magnetic iron oxide nano (ufIONP) as a core carrier, the advantages of the ultrafine nano-carrier, including high permeability and sustained release, the targeted delivery effect of ovarian cancer is improved by loading targeted ligand folic acid (FA which is highly expressed by various tumors) on the surface of the drug, and meanwhile, the drug delivery effect and the side effect of anticancer irinotecan derivative SN-38(FA-ufIONP-SN38) are compared with the curative effect and the side effect of treating advanced peritoneal metastasis of ovarian cancer by singly using the anticancer drug SN38 and the conventional 50nm drug-loaded particles through intraperitoneal delivery (i.p.) respectively.
The nano-targeting sustained-release drug provided by the embodiment solves the problems of difficult penetration of chemotherapeutic drugs to deep parts of tumors, short drug action time, no targeting property and safe drug use in the abdominal cavity drug delivery (i.p.) treatment process of patients with advanced ovarian cancer at present, and provides a high-efficiency, targeting and sustained-release carrier, so that the carrier has the effects of prolonging the action time of the drugs on the tumors, effectively penetrating to deep parts of the tumors in a targeting manner, killing tumor cells, reducing the drug use dose and relieving normal tissue damage after carrying the drugs. The problems that clinical abdominal cavity drug delivery (i.p.) chemotherapy drugs lack high efficiency, targeting, slow release efficiency, drug safety and the like are solved.
Furthermore, the carrier after the medicine is loaded by the ultrafine nanometer medicines can be metabolized from the body quickly, the detention time in the liver is avoided, the safety of pharmacokinetics is improved, the harm of the whole body toxic and side effects caused by increasing the medicine dosage to meet the medicine effect and repeated medicine application in clinic is effectively solved, and the safety of the carrier in clinical application is improved.
Referring to fig. 1, fig. 1 is a schematic flow chart of a first embodiment of a method for preparing a nano-targeted sustained release drug, which is provided by the present invention, and the method includes:
step S10, constructing the drug-carrying nanomaterial based on the pre-prepared ultra-small magnetic iron oxide nano ufIONP;
and step S20, infusing chemotherapeutic drugs onto the drug-carrying nanometer material to generate the nanometer targeted sustained-release drug.
In the embodiment, the prepared ultra-small magnetic iron oxide nano ufIONP is used as a core carrier of a nano targeted slow-release drug, and a chemotherapeutic drug is loaded on a drug loading material of the ultra-small magnetic iron oxide nano ufIONP to generate the nano targeted slow-release drug, so that a specific efficient drug carrier with targeting and slow-release effects is constructed by using the advantage of the 'superfine' microstructure of the ultra-small magnetic iron oxide nano ufIONP nano material, the problem that the abdominal cavity drug delivery (i.p.) lacks targeting, low efficiency and no slow-release efficiency in clinic is solved, and the effect of the i.p. chemotherapy on specifically treating advanced ovarian cancer is improved.
The respective steps will be described in detail below:
step S10, constructing the drug-carrying nanomaterial based on the pre-prepared ultra-small magnetic iron oxide nano ufIONP;
in a specific embodiment, the ultra-small magnetic iron oxide nano ufIONP is prepared by adopting an in-situ particle polymerization method and an ultrathin coating technology, the nano carrier of the ultra-small magnetic iron oxide nano ufIONP has a perfect 3nm 'ultra-fine' carrier, has a larger specific surface area compared with other medicine carrying structures, can bear more chemotherapeutic medicines and group links with different functions by utilizing the 'ultra-fine' nano carrier of the nano material, and becomes an efficient, safe, targeted and visualized 'ultra-fine' medicine carrying nano material with multiple functions while increasing the dosage of anticancer medicines.
Specifically, in the in-situ particle polymerization method, the composite material is constructed by the nano particles and the organic polymer material, and the reaction monomers are filled between the layers of the nano-layered material to generate a polymerization reaction between the layers to generate a polymer substance; the ultra-thin coating technology is to distribute the polymeric substance obtained by the in-situ particle polymerization method on the surface of the ultra-small magnetic iron oxide nano ufIONP to form the drug-carrying nano material with the unique structural advantage of 'ultra-thin'.
Referring to fig. 2, step S10 specifically includes:
step S11, filling targeting ligand folic acid serving as a prepolymer into the interlayer of a pre-prepared ultra-small magnetic iron oxide nano ufIONP laminate;
step S12, loading irinotecan derivatives as pre-reactants between the layers of the prepared ultra-small magnetic iron oxide nano ufIONP;
step S13, carrying out polymerization reaction between the targeted ligand folic acid and the irinotecan derivative between the lamellar layers of the ultra-small magnetic iron oxide nano ufIONP to obtain a polymeric substance of the targeted ligand folic acid;
step S14, depositing the polymer substance between the layered substance layers of the ultra-small magnetic iron oxide nanometer ufIONP to obtain the drug-carrying nanometer material.
In a specific embodiment, the successfully prepared ultra-small magnetic iron oxide nano ufIONP is used as a core carrier, the nano has the unique advantages of a superfine structure, including high permeability and slow release, a targeting ligand folic acid FA is loaded on the surface of the nano, a plurality of tumors in the targeting ligand folic acid FA are highly expressed to improve the targeted drug delivery effect of ovarian cancer, and meanwhile, an anticancer drug irinotecan derivative SN-38(FA-ufIONP-SN38) is loaded to generate a drug-loaded nano material with the unique structure advantage of superfine.
And step S20, infusing chemotherapeutic drugs onto the drug-carrying nanometer material to generate the nanometer targeted sustained-release drug.
Referring to fig. 3, step S20 specifically includes:
and step S21, carrying the chemotherapeutic drug through the functional reaction group on the drug carrying nanometer material to generate the nanometer targeted sustained-release drug.
In a specific embodiment, a chemotherapeutic drug is loaded on the drug-loaded nanomaterial, and folic acid targeted modification is performed through a large number of functional reaction groups on the surface of the drug-loaded nanomaterial, so that the drug loading rate of the anticancer drug is increased.
In the embodiment, the prepared ultra-small magnetic iron oxide nano ufIONP is used as a core carrier of a nano targeted slow release medicament, a chemotherapy medicament is loaded on a medicament carrying material of the ultra-small magnetic iron oxide nano ufIONP to generate a nano targeted slow release medicament, and a specific efficient medicament carrier with targeting and slow release effects is constructed by using the advantage of the 'superfine' microstructure of the ultra-small magnetic iron oxide nano ufIONP nano material, so that the problem that the abdominal cavity medicament (i.p.) delivery lacks targeting, low efficiency and no slow release efficiency in clinic is solved, and the effect of the abdominal cavity medicament (i.p.) chemotherapy on specifically treating advanced ovarian cancer is improved.
Further, based on the first embodiment of the preparation method of the nano-targeted sustained release drug of the embodiment, the second embodiment of the preparation method of the nano-targeted sustained release drug of the invention is provided.
The difference between the second embodiment of the method for preparing a nano-targeted sustained release drug and the first embodiment of the method for preparing a nano-targeted sustained release drug is that, in this embodiment, after step S20, the method for preparing a nano-targeted sustained release drug further includes a scheme for testing the targeting property and the drug loading effect of the nano-targeted sustained release drug, and after step S20, the method further includes:
and step S200, testing the targeting property and the drug loading effect of the nano targeted sustained-release drug.
Referring to fig. 4, fig. 4 is a specific step of step S200 of the method for preparing a nano-targeted sustained release drug according to the present embodiment, wherein in step S200, after the preparation of the nano-targeted sustained release drug is completed, the targeting property and the drug action of the nano-targeted sustained release drug need to be detected, and when the targeting property and the drug action of the nano-targeted sustained release drug reach a preset standard, the nano-targeted sustained release drug can be used.
Referring to fig. 5, step S200 specifically includes:
step S201, detecting the targeting property and the drug loading effect of the nano targeted sustained release drug by adopting a cell activity detection technology MTT;
in a specific embodiment, the anti-tumor effect of the nano-targeting sustained-release drug is researched at a cellular level, and the research method comprises the steps of selecting SKOV-3 cells of an ovarian cancer cell line, adopting an MTT cell activity detection technology to observe the targeting property and the drug-loading efficiency of the superfine nano-targeting sustained-release drug, evaluating the safety of the nano-targeting sustained-release drug at a cellular level, selecting normal ovarian cells and immune cells (macrophages), adopting the MTT cell activity to detect the toxic effect of the superfine nano-carrier, and evaluating the toxicity of the ufIONP on the normal somatic cells and the immune cells.
Specifically, human ovarian cancer cell line SKOV-3 and macrophage line RAW264.7 are taken as experimental objects to carry out in-vitro cytology research, and the performances of the chemotherapeutic drugs clinically used at present and different control groups commonly used for 50nm particle drug loading are respectively detected in the aspects of drug loading efficiency, drug release curve, intracellular drug concentration and cytotoxicity test, so that the high efficiency and the safety of the ultrafine nano targeted delivery drugs are researched.
Step S202, if the targeting property and the drug loading effect of the nano targeted sustained release drug reach preset standards, the nano targeted sustained release drug can be used;
step S203, if at least one of the targeting property and the drug loading effect of the nano targeted sustained release drug does not meet a preset standard, the nano targeted sustained release drug is unavailable.
In a specific embodiment, the toxicity of normal somatic cells and immune cells is evaluated to obtain corresponding evaluation results, further usability judgment is carried out according to whether the detected drug loading efficiency, drug release curve, intracellular drug concentration and performance data in the aspect of cytotoxicity test reach preset standards, and if the detected drug loading efficiency, drug release curve, intracellular drug concentration and performance data in the aspect of cytotoxicity test of the nano targeted sustained-release drug reach the preset standards, the nano targeted sustained-release drug can be used; if at least one of the performance data in the aspects of the drug loading efficiency, the drug release curve, the intracellular drug concentration and the cytotoxicity test detected by the nano targeted sustained-release drug does not meet the preset standard, the nano targeted sustained-release drug is unavailable.
In the embodiment, the targeting property and the drug loading effect of the nano-targeted sustained-release drug are detected by adopting a cell activity detection technology MTT, the toxicity of the drug administration safety of the nano-targeted sustained-release drug is detected, the carrier after the 'superfine' nano drug loading can be rapidly metabolized from the body, the residence time in the liver is avoided, the safety of pharmacokinetics is improved, the harm of the whole body toxic and side effects caused by increasing the drug administration dose to meet the drug effect and repeated drug administration in clinic is effectively solved, and the safety of the nano-targeted sustained-release drug in clinical application is improved.
Further, based on the first and second embodiments of the method for preparing a nano-targeted sustained release drug of the present invention, a third embodiment of the method for preparing a nano-targeted sustained release drug of the present invention is provided.
The third embodiment of the method for preparing a nano-targeted sustained release drug is different from the first and second embodiments of the method for preparing a nano-targeted sustained release drug in that, after step S202, if the nano-targeted sustained release drug is available, the method for preparing a nano-targeted sustained release drug further includes a scheme for applying the nano-targeted sustained release drug, and after step S202, the method further includes:
step S2020, the nano targeted sustained release medicine is applied to performance data acquisition.
Referring to fig. 6, fig. 6 is a specific step of step S202 of the method for preparing a nano-targeted sustained release drug according to the present embodiment, and step S202 is to apply the nano-targeted sustained release drug after detecting that the targeting property and the drug loading property of the nano-targeted sustained release drug meet preset standards.
Referring to fig. 7, step S2020 specifically includes:
step S2021, culturing cancer cells by simulating growth conditions in vivo of the cancer cells;
step S2022, incubating the cancer cells and the nano-targeting sustained-release medicine to obtain a cancer cell animal model;
step S2023, transferring the nano-targeting sustained-release drug to the cancer cell animal model by an intraperitoneal perfusion drug delivery mode to obtain performance data of the nano-targeting sustained-release drug.
In some embodiments, after completing the construction of the nano-targeted sustained-release drug, the method further comprises the application of collecting performance data of the nano-targeted sustained-release drug, and researching the anti-tumor effect from animal level: selecting a athymic nude mouse, adopting a humanized ovarian cancer (PDX) abdominal cavity transfer model to observe a superfine nano-targeted slow release carrier, delivering a medicament through an abdominal cavity delivery way to treat the curative effect of advanced ovarian cancer, acquiring the performance data of the nano-targeted slow release medicament, evaluating the safety of the animal level, and observing the pharmacokinetic change of the normal nude mouse after the normal nude mouse is infused with the nano-targeted slow release medicament, wherein the data comprises the following steps: the half-life period of the drug in blood, the distribution, absorption and elimination of each main organ, and the safety of the drug delivery of the 'superfine' nano targeting sustained-release carrier is evaluated.
The respective steps will be described in detail below:
step S2021, culturing cancer cells by simulating growth conditions in vivo of the cancer cells;
in one embodiment, ovarian cancer cells are seeded into cell culture plates to simulate in vivo desired growth conditions, including temperature and nutrient data, by culturing the ovarian cancer cells in growth conditions that simulate good growth conditions.
Step S2022, incubating the cancer cells and the nano-targeting sustained-release medicine to obtain a cancer cell animal model;
in one embodiment, the application objects are ovarian cancer cell lines highly expressing folate receptors and a human-derived ovarian cancer abdominal cavity metastasis animal (mouse) model; the application mode is that the ovarian cancer cells are applied by culture, and the ovarian cancer animal model adopts abdominal cavity perfusion chemotherapy injection.
Step S2023, transferring the nano-targeting sustained-release drug to the cancer cell animal model by an intraperitoneal perfusion drug delivery mode to obtain performance data of the nano-targeting sustained-release drug.
In one embodiment, the treatment, observation, and comparison of efficacy and side effects between groups were performed by intraperitoneal delivery of the drug under different conditions on a peritoneal metastasis PDX model of ovarian cancer. Efficacy is expressed in Complete Remission (CR), Partial Remission (PR), disease Stability (SD), disease Progression (PD), and the evaluation method comprises: imaging examination, blood biochemical examination, and pathological examination of tumor and important organs. The curative effect and the side effect of the ultrafine nano targeted delivery slow-release medicine for treating the peritoneal metastasis of the advanced ovarian cancer by intraperitoneal delivery are further researched by an in-vivo advanced ovarian cancer model. Whether the targeted ultrafine nano drug-loaded medicine has the effect of improving the abdominal cavity drug delivery curative effect on the late ovarian cancer peritoneal metastasis is verified through in vitro cell experiments and in vivo animal experiments, and the method specifically comprises the following steps: targeted adsorption capacity, concentration and depth of medicine penetrating into tumor, retention time for maintaining medicine effect, and visual early evaluation of curative effect.
Specifically, the device for performing detection is a visual monitoring device, for example, the monitoring device is MRI; the application comprises the following specific steps: inoculating the corresponding ovarian cancer cells into a cell culture plate, simulating growth conditions required in vivo, wherein the growth conditions comprise temperature, nutrition and the like, incubating the ovarian cancer cells with high-efficiency targeted sustained-release agents such as FA-uIONP/SN38, uIONP-SN38 and Free SN38, measuring the drug loading efficiency, the drug release curve, the intracellular drug concentration and the performance in cytotoxicity test, and acquiring corresponding performance data, and injecting the FA-uIONP/SN38, uIONP-SN38 and Free SN38 into an ovarian cancer abdominal cavity transfer body through an abdominal cavity drug delivery way, and measuring the drug hemodynamics to acquire corresponding measured data.
In the embodiment, the nano targeted sustained-release drug is transferred to a cancer cell animal model, performance data monitoring is performed through visual monitoring of the nano targeted sustained-release drug, based on the current situation that the late-stage abdominal perfusion treatment of the ovarian cancer lacks an efficient targeted sustained-release agent and the curative effect of the nano targeted sustained-release drug is visually monitored, a multifunctional visual ultrafine nano carrier drug loaded with a targeted ligand is planned to be constructed on the basis of the early-stage research, the curative effect of the late-stage ovarian cancer is improved through an (i.p.) chemotherapy approach, and the curative effect and the side effect of the ultrafine nano targeted delivery sustained-release drug for treating the late-stage ovarian cancer peritoneal metastasis through abdominal drug delivery of the ultrafine nano targeted delivery sustained-release drug are further researched for the late-stage ovarian cancer model in vivo through evaluation methods such as imaging examination, hematology chemical examination, pathological examination of tumors and important organs and the like.
The invention also provides a preparation device of the nano targeted sustained-release medicine. Referring to fig. 8, the apparatus for preparing a nano-targeted sustained release drug of the present invention comprises:
a construction module 10 for constructing the drug-loaded nanomaterial based on a pre-prepared ultra-small magnetic iron oxide nanomaterial;
and the perfusion module 20 is used for perfusing chemotherapeutic drugs to the drug carrying nanometer material to generate the nanometer targeted sustained-release drug.
In the embodiment of the apparatus for preparing a nano-targeted sustained release drug of the present invention, all technical features of the embodiments of the method for preparing a nano-targeted sustained release drug are included, and the description and explanation contents are basically the same as those of the embodiments of the method for preparing a nano-targeted sustained release drug, and are not repeated herein.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or system that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or system. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, method, article, or system that comprises the element.
The above-mentioned serial numbers of the embodiments of the present invention are merely for description and do not represent the merits of the embodiments.
The above description is only a preferred embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, which are made by using the contents of the present specification and the accompanying drawings, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (9)
1. A nano-targeted slow-release drug is characterized by comprising:
the surface of the drug-loaded nanomaterial carries a functional reactive group;
and the chemotherapeutic drugs are loaded on the functional reaction groups on the surfaces of the drug-loaded nano materials through solution impregnation.
2. The nano-targeted slow-release drug according to claim 1,
the drug-carried nano material is used as a core carrier of the chemotherapeutic drug;
the surface of the drug-loaded nanomaterial is loaded with a targeting ligand folic acid;
the targeted ligand folic acid carried on the nanometer material of the drug adsorbs irinotecan derivatives.
3. A preparation method of a nano-targeted slow-release medicine is characterized by comprising the following steps:
constructing the drug-loaded nanomaterial based on pre-prepared ultra-small magnetic iron oxide nano ufIONP;
and (3) infusing chemotherapeutic drugs onto the drug carrying nanometer material to generate the nanometer targeted slow-release drug.
4. The method for preparing a nano-targeted sustained release drug according to claim 3, wherein the step of constructing the drug-loaded nanomaterial based on the pre-prepared ultra-small magnetic iron oxide nano ufIONP comprises:
filling targeted ligand folic acid serving as a prepolymer into the interlayer of a pre-prepared ultra-small magnetic iron oxide nano ufIONP laminate;
loading irinotecan derivatives serving as a pre-reactant into the interlayer of a layer of the prepared ultra-small magnetic iron oxide nano ufIONP;
polymerizing the targeted ligand folic acid with the irinotecan derivative between the lamellar layers of the ultra-small magnetic iron oxide nano ufIONP to obtain a polymeric substance of the targeted ligand folic acid;
and depositing the polymeric substance between the layers of the ultra-small magnetic iron oxide nano ufIONP to obtain the drug-loaded nano material.
5. The method for preparing a nano-targeted slow-release drug according to claim 3, wherein the step of infusing a chemotherapeutic drug onto the drug-loaded nanomaterial to generate the nano-targeted slow-release drug comprises:
and carrying the chemotherapeutic drug by the functional reaction group on the drug carrying nano material to generate the nano targeted slow release drug.
6. The method for preparing a nano-targeted sustained release drug according to claim 3, wherein after the step of infusing a chemotherapeutic drug onto the drug-loaded nanomaterial to generate the nano-targeted sustained release drug, the method for preparing a nano-targeted sustained release drug further comprises:
detecting the targeting property and the drug loading effect of the nano-targeted sustained-release drug by adopting a cell activity detection technology MTT;
if the targeting property and the drug loading effect of the nano-targeted sustained-release drug reach preset standards, the nano-targeted sustained-release drug can be used;
if at least one of the targeting property and the drug loading effect of the nano targeted sustained-release drug does not meet the preset standard, the nano targeted sustained-release drug is unavailable.
7. The method for preparing a nano-targeted slow-release medicament according to claim 6, wherein after the step of using the nano-targeted slow-release medicament if the targeting property and the medicament loading effect of the nano-targeted slow-release medicament both meet the preset standards, the method for preparing the nano-targeted slow-release medicament further comprises the following steps:
culturing cancer cells by simulating growth conditions in vivo;
incubating the cancer cells and the nano-targeted sustained-release drug to obtain a cancer cell animal model;
transferring the nano-targeted sustained-release drug to the cancer cell animal model by an intraperitoneal perfusion drug delivery mode to obtain performance data of the nano-targeted sustained-release drug.
8. A preparation device of nano-targeted slow-release medicine is characterized by comprising the following components:
the construction module is used for constructing the drug-loaded nanomaterial based on the prepared ultra-small magnetic iron oxide nanoparticles;
and the perfusion module is used for perfusing chemotherapeutic drugs to the drug carrying nanometer material to generate the nanometer targeted sustained-release drug.
9. Use of the nano-targeted slow-release medicament as claimed in any one of claims 1 to 2 in anti-tumor and anti-cancer treatment.
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