DRUG COMPRISING PLGA NANOPARTICLES LOADED WITH CAPE TARGETED WITH ANGIOPEP-2 PEPTIDE

Abstract

A cancer drug for use in the treatment of cancer in which caffeic acid phenethyl ester (CAPE) is encapsulated in poly [lactic-co-glycolic acid] (PLGA) to increase its solubility in aqueous media is provided. Angiopep-2 is used as a specific ligand to increase biological activity. In an embodiment of the invention, PLGA is preferably in the form of nanoparticles, thereby ensuring better solubility.

Claims

1. A drug for a use in treating a cancer, comprising caffeic acid phenethyl ester (CAPE) encapsulated in poly [lactic-co-glycolic acid] (PLGA).

2. The drug according to claim 1, further comprising angiopep-2 attached to a surface of the PLGA, as a targeter.

3. The drug according to any one of claim 1 , wherein the PLGA is in a form of nanoparticles.

4. The drug according to any one of claim 1, wherein the drug is used to treat glioma.

5. The drug according to claim 2, wherein the PLGA is in a form of nanoparticles.

6. The drug according to claim 2, wherein the drug is used to treat glioma.

7. The drug according to claim 3, wherein the drug is used to treat glioma.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0022] In the state of the art, there is no publication about CAPE loaded PLGA nanoparticles directly targeted with angiopep-2; and studies investigating CAPE, PLGA and angiopep-2 peptide, individually, have already been listed. Various studies on the drug delivery systems in which is aimed to overcome the low water solubility problem of the CAPE molecule have been mentioned in the background art section above. Although the above-mentioned articles in the prior art provide a solution to water solubility, the amount of CAPE used is quite low and it has disadvantages against the problem of water solubility that is aggravated in increasing amounts. In the International Application Publication No. WO 2019/132831 A2, the CAPE molecule was targeted against neuroblastoma cancer cells using exosomes, and ligands were not used specifically for targeting. In the state of the art, there is no solution for improving the cytotoxic activity and yet targeting the molecule with cell-specific ligands.

[0023] In the present improvement, a PLGA-based polymeric carrier is used because of its biocompatible and biodegradable behavior. Targeting is provided by the angiopep-2 peptide. The drug delivery systems of the present application, targeted with cell-specific ligands, both increase the water solubility of the molecule and increase biological activity by triggering various receptor-mediated cell entry mechanisms.

[0024] The delivery system used in the present improvement is a synthetic polymer, and specifically only the blood brain barrier and glioma cells are targeted with the angiopep-2 peptide. Synthetic PLGA nanoparticles are approved by the FDA and are suitable for use in humans and other living organisms. PLGA is used for the specific delivery of the CAPE, and to increase its solubility in water. The CAPE molecule is encapsulated in PLGA polymeric nanoparticles, so that its water solubility is increased. Meanwhile, angiopep-2 peptide is attached to the surface of the nanoparticles, and the LRP-1 receptor located on the blood brain barrier endothelial cells and on the surface of glioma cells is targeted. Thus, selectivity in treatment is provided and the biological activity of the molecule is increased.

[0025] Thus, the present invention provides a drug containing PLGA with CAPE encapsulated therein, and angiopep-2 that is preferably attached to the surface thereof. CAPE is used as a cytotoxic agent, thus ensuring the biological activity of the drug delivery system obtained as a product. CAPE is provided encapsulated in PLGA.

[0026] In a preferred embodiment of the invention, Angiopep-2 is used in the product in order to target CAPE to the brain barrier and glioma cells, so that a high biological activity is ensured. Accordingly, a preferred embodiment of the present invention is a drug containing angiopep-2. Angiopep-2 may be located on the surface of the PLGA.

[0027] PLGA blocks are hydrophobic and may be produced in nanoparticular structure to confine CAPE. Thus, a preferred embodiment of the product of the present application is a drug containing PLGA nanoparticles with CAPE encapsulated therein. Preferably, angiopep-2 is located on the surface of the said PLGA nanoparticles.

[0028] In an exemplary embodiment of the invention, a drug formulation is provided that can cross the blood brain barrier, for the treatment of patients having tumors of the central nervous system or glioma brain tumors. CAPE loaded nanoparticles targeted with the angiopep-2 peptide can bind to the LRP-1 receptors in the blood-brain barrier endothelial cells by means of the said peptide and pass into the central nervous system via transcytosis (i.e., receptor-mediated transcytosis). Thanks to the effect of the CAPE molecule in the treatment of the central nervous system diseases and glioma, the treatment may be performed with high efficiency. With the targeting angiopep-2 peptide, glioma cells may also be specifically targeted, thereby making it possible to achieve selectivity in treatment and to cross the blood-brain barrier.

[0029] The water solubility of the CAPE molecule with known biocompatibility is increased by present improvement. The drug provided may also be used as an interim treatment drug that will not cause any side effects between chemotherapy sessions, as it provides cell/tissue-specific targeting.

[0030] It has been concluded that the cytotoxic activity of the product synthesized and characterized in laboratory studies on glioma cells is higher than the free CAPE.

[0031] With the improvement of the invention, the following objectives have been achieved: [0032] the deficiencies in the state of the art have been eliminated, problems have been solved; [0033] a cancer drug with high solubility, particularly a drug for glioma, is provided; [0034] a high pharmacokinetic activity of the said drug is also obtained.