Pharmaceutical composition combining at least two distinct nanoparticles and a pharmaceutical compound, preparation and uses thereof
Inventors
Germain, Matthieu • Meyre, Marie-Edith • Pottier, Agnès • Levy, Laurent
Assignees
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Publication Number
US-11471410-B2
Publication Date
2022-10-18
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition comprising the combination of (i) at least two distinct biocompatible nanoparticles and (ii) at least one compound of interest, typically at least one pharmaceutical compound, to be administered to a subject in need of such at least one compound of interest, wherein the at least two distinct biocompatible nanoparticles potentiate the compound(s) of interest efficiency. The at least two biocompatible nanoparticles can be administered sequentially or simultaneously to the subject but are to be administered separately, typically with an interval of between more than about 5 minutes and about 72 hours, from the at least one compound of interest, preferably before the administration of the at least one compound of interest, to said subject. The longest dimension of the at least two biocompatible nanoparticles is typically between about 4 nm and about 500 nm. The absolute surface charge value of a first biocompatible nanoparticle is of at least |10 mV| and the absolute surface charge value of the second biocompatible nanoparticle, or of any additional biocompatible nanoparticle, has a difference of at least 10 mV with the absolute surface charge value of the first biocompatible nanoparticle.
Core Innovation
The invention relates to a method of treating a subject having a disease by administering at least one pharmaceutical compound and, in a distinct step, at least two distinct biocompatible nanoparticles. The nanoparticles have a defined size range, where the longest dimension of each nanoparticle is between about 4 nm and about 500 nm, and they are administered separately from the pharmaceutical compound with a defined time interval.
A key part of the method is that the two or more distinct biocompatible nanoparticles have defined negative surface charge values. A first biocompatible nanoparticle has a negative charge below −10 mV, and a second biocompatible nanoparticle or any additional biocompatible nanoparticle has a negative surface charge with a difference of at least 10 mV relative to the negative surface charge value of the first biocompatible nanoparticle.
The described approach is presented as maintaining or improving therapeutic, prophylactic, or diagnostic benefit while reducing toxicity. The disclosure includes liposome nanoparticles and other organic or inorganic biocompatible nanoparticles, with surface-charge concepts such as zeta potential and the use of biocompatible coatings.
Claims Coverage
The provided independent claim sets out three main inventive feature groups: nanoparticle composition parameters, distinct negative surface charges, and separate administration timing relative to the pharmaceutical compound.
Separately administered distinct biocompatible nanoparticles with defined size
Administering at least two distinct biocompatible nanoparticles in a distinct step, where the longest dimension of each nanoparticle is between about 4 nm and about 500 nm, and each nanoparticle is not used as the at least one pharmaceutical compound.
Distinct negative surface charges with at least 10 mV separation
Where the surface charge value of a first biocompatible nanoparticle is a negative charge below −10 mV, and the surface charge value of a second or additional biocompatible nanoparticle is negative and differs by at least 10 mV from the first biocompatible nanoparticle.
Separate timing between nanoparticles and the pharmaceutical compound
Administering the at least two distinct biocompatible nanoparticles separately from the at least one pharmaceutical compound between 5 minutes and about 24 hours before the at least one pharmaceutical compound.
Overall, the claim coverage centers on delivering at least two distinct biocompatible nanoparticles with specified size and distinct negative surface charges, administered separately before the pharmaceutical compound within a defined time window.
Stated Advantages
Maintaining or improving therapeutic, prophylactic, or diagnostic benefit while reducing toxicity.
Enabling at least 10% dose reduction versus standard dosing.
Documented Applications
A method of treating a subject having a disease, including therapeutic, prophylactic, or diagnostic benefit as described in the disclosure.
In vivo mouse xenograft efficacy and toxicity assessment, including tumor volume measurement and toxicity assessment using Dox-NP® liposomal encapsulated doxorubicin.
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