Pegylated nanoparticles
The present invention relates to nanoparticles comprising a biodegradable polymer, preferably the vinyl methyl ether and maleic anhydride (PVM/MA) copolymer, and a polyethylene glycol or derivatives thereof. These nanoparticles are easy to produce and provide excellent bioadhesion, size and zeta potential characteristics making them suitable for the administration of active molecules. The selection of the type of polyethylene glycol used in their production allows suitably modulating the characteristics of these nanoparticles, which can be advantageously used according to the type of drug to be carried and/or the method of administration of the pharmaceutical formulation. pegylation is carried out by simple incubation for a short time period of the two macromolecules in question, without needing to have to resort to the use of organic solvents with high toxicity or long and laborious organic synthesis processes. Furthermore, the pegylation process can be associated to the process of encapsulating the biologically active molecule.
1. Oral pegylated nanoparticles for carrying biologically active molecules comprising a pegylated biodegradable polymer, said biodegradable polymer being a vinyl methyl ether and maleic anhydride (PVM/MA) copolymer, said pegylated nanoparticles having increased intestinal mean residence time as compared with nanoparticles of PVM/MA lacking PEG, and wherein said pegylated nanoparticles are pegylated with a polyethylene glycol (PEG) or a derivative thereof having a molecular weight between 1,500 and 10,000 Da.
2. Nanoparticles according to claim 1 , wherein the copolymer has a molecular weight between 200 and 2000 KDa.
3. Nanoparticles according to claim 1 , wherein the weight ratio between polyethylene glycol and the biodegradable polymer is 1:2-4.
4. Nanoparticles according to claim 1 , wherein the biologically active molecule is a protein or peptide.
5. Nanoparticles according to claim 1 , wherein the biologically active molecule is selected from the group consisting of DNA, RNA, nucleosides, nucleotides, oligonucleotides or polynucleotides.
6. Nanoparticles according to claim 1 , wherein the biologically active molecule is an anti-tumor agent or an antigen for tumors.
7. Nanoparticles according to claim 1 , wherein the biologically active molecule is a protective agent of the central nervous system or a glucocorticoid.
8. Nanoparticles according to claim 1 , wherein the biologically active molecule is an antigen for vaccination or an allergen for immunotherapy.
9. A pharmaceutical composition comprising the pegylated nanoparticles of claim 1 , further comprising an excipient, carrier or adjuvant.
10. A pharmaceutical composition according to claim 9 adapted for administration by a route providing access to a mucosa.
11. A pharmaceutical composition according to claim 10 for oral administration.
12. A method of orally administering a therapeutic agent to a subject, said method comprising delivering the therapeutic agent to said subject in the nanoparticle of claim 1 .
13. A lyophilizate comprising pegylated nanoparticles according to claim 1 .
14. A process of preparing the pegylated nanoparticles of claim 1 said process comprising a first step of simultaneous incubation of the biodegradable polymer and polyalkylene glycol in an organic solvent, followed by a second step of desolvating the polymer with a hydroalcoholic solution.
15. A process according to claim 14 , characterized by at least one of the following:
(a) removal of organic solvents and/or purification;
(b) addition of an active molecule during the simultaneous incubation of the biodegradable polymer and the polyalkylene glycol in an organic solvent; and
(c) an additional lyophilization, optionally in the presence of a cryoprotective agent.
16. A process according to claim 15 , wherein the active molecule is added in the step of simultaneous incubation of the biodegradable polymer and the polyalkylene glycol in an organic solvent.
17. A process according to claim 15 , comprising lyophilization step in the presence of a cryoprotective agent selected from the group consisting of sucrose and mannitol.
18. A process according to claim 15 , wherein said copolymer has a molecular weight between 100 and 2400 kDa.