Nanoparticles for encapsulating compounds, the preparation and uses thereof
Inventors
Irache Garreta, Juan Manuel • HUARTE CIGANDA, Judit • INCHAURRAGA CASADAMÓN, Laura • RUIZ GATÓN, Luisa Fernanda • MARTÍN ARBELLÁ, Nekane
Assignees
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Publication Number
US-10933025-B2
Publication Date
2021-03-02
Expiration Date
Abstract
The present invention relates to nanoparticles for encapsulating biologically active compounds, comprising a matrix of new polymer conjugates. The invention also relates to a process for producing both the conjugates and nanoparticles, to compositions containing said conjugates or nanoparticles, and applications thereof. The invention is applicable in the pharmaceutical sector and in the nanotechnology sector.
Core Innovation
The invention relates to poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA)-based ester polymer conjugates in which anhydride units are esterified with a hydroxyl-terminated molecule selected from polyethylene glycol (PEG) and a derivative thereof containing a hydroxyl-terminal reactive group.
The invention addresses producing nanoparticles by mixing the ester polymer conjugate with a biologically active compound in an organic medium and then desolvating the ester polymer conjugate by adding alcohol and water in the presence of a divalent metal. This process forms nanoparticle compositions in which the biologically active compound is associated with the PVM/MA ester polymer conjugate.
The described rationale is directed to gastrointestinal (GI) tract drug delivery, including mucus layer crossing and interaction with enterocytes, as well as sustained plasma levels. Documented uses include oral delivery and antitumor treatment, with examples using docetaxel, paclitaxel, and camptothecin, together with discussion of pharmacokinetic exposure and biodistribution.
Claims Coverage
The patent includes one independent claim that broadly covers a process for producing nanoparticles from a PVM/MA-based ester polymer conjugate and a biologically active compound, followed by desolvation in the presence of a divalent metal. Dependent claims refine the main inventive elements by specifying PEG options, selected processing constraints, and pharmaceutical composition embodiments with antitumor agents.
Nanoparticle production by mixing PVM/MA ester polymer conjugate with a biologically active compound and desolvating in presence of a divalent metal
A process for producing a nanoparticle comprising mixing an ester polymer conjugate with a biologically active compound in an organic medium, and desolvating the ester polymer conjugate by adding alcohol and water in the presence of a divalent metal; wherein the ester polymer conjugate is a conjugate of poly(methyl vinyl ether-co-maleic anhydride) with a hydroxyl-terminated molecule selected from a polyethylene glycol and a derivative thereof containing a hydroxyl-terminal reactive group.
Specific weight ratio between ester polymer conjugate and biologically active compound in the mixing step
The process further limits the mixture in step a) such that a weight ratio of ester polymer conjugate to biologically active compound is 1:0.01–0.20.
Hydroxyl-terminated PEG molecular-weight options
The process further specifies that the hydroxyl-terminated molecule is selected from PEG1, PEG2, PEG6, and PEG10.
Hydroalcoholic mixture with divalent metal for the desolvation step
The process further specifies that step b) is carried out by adding a hydroalcoholic mixture containing a divalent metal to the mixture produced in step a).
Organic medium limited to acetone
The process further specifies that the organic medium used is acetone.
Pharmaceutical composition with specified PEG/PVM/MA conjugates, antitumor agents, calcium, and a saccharide
A pharmaceutical composition selected from specified compositions containing an ester polymer conjugate of poly(methyl vinyl ether-co-maleic anhydride) with polyethylene glycol 2,000 or metoxi-polyethylene glycol 2,000, along with docetaxel or camptothecin, calcium, and a saccharide, with proportions defined by weight of the total composition.
Overall, the claim set centers on producing nanoparticles from PVM/MA ester polymer conjugates where PEG hydroxyl-terminated molecules and derivatives are conjugated, then forming nanoparticles by mixing with a biologically active compound and desolvating with alcohol/water in the presence of a divalent metal. Dependent claims narrow the PEG identity options, constrain mixing proportions, specify the organic medium as acetone, refine the desolvation medium definition, and provide detailed pharmaceutical composition embodiments including antitumor agents.
Stated Advantages
Extended/sustained plasma exposure.
Improved oral bioavailability.
Mucus penetration and interaction with enterocytes (documented by fluorescence microscopy in the provided description).
Documented Applications
Oral drug delivery in the gastrointestinal (GI) tract, including mucus layer crossing and enterocyte interaction.
Cancer treatment/antitumor treatment using nanoparticles/compositions associated with docetaxel, paclitaxel, and camptothecin.
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