Invention for Drug delivery compositions
Invented by Victor C. Yang, Yoon Jeong Park, Junfeng Liang, University of Michigan
One of the key factors driving the growth of the drug delivery compositions market is the rising prevalence of chronic diseases such as cancer, diabetes, and cardiovascular disorders. These conditions require long-term medication, and drug delivery compositions offer a convenient and effective way to administer drugs. Moreover, the aging population and the increasing burden of diseases have further fueled the demand for advanced drug delivery systems.
The market for drug delivery compositions is also being propelled by advancements in technology and innovation. Researchers and pharmaceutical companies are constantly developing novel drug delivery systems to overcome the limitations of conventional drug formulations. For instance, nanotechnology-based drug delivery systems have gained significant attention in recent years due to their ability to enhance drug solubility, bioavailability, and targeted delivery.
Furthermore, the increasing focus on personalized medicine and precision therapeutics has further boosted the demand for drug delivery compositions. These compositions enable the delivery of drugs to specific cells or tissues, thereby maximizing therapeutic outcomes while minimizing systemic toxicity. This targeted approach has the potential to revolutionize the treatment of various diseases, including cancer.
The market for drug delivery compositions is highly competitive, with several key players operating in the industry. These companies are investing heavily in research and development activities to develop innovative drug delivery systems. Additionally, strategic collaborations and partnerships are being formed to leverage the expertise of different stakeholders and accelerate the development and commercialization of drug delivery compositions.
Geographically, North America dominates the drug delivery compositions market, owing to the presence of a well-established healthcare infrastructure, increasing R&D investments, and a favorable regulatory environment. However, the Asia Pacific region is expected to witness significant growth in the coming years, driven by the rising healthcare expenditure, increasing patient population, and growing awareness about advanced drug delivery systems.
Despite the promising growth prospects, the market for drug delivery compositions faces certain challenges. High development costs, stringent regulatory requirements, and the risk of product failure are some of the factors that may hinder market growth. Additionally, the lack of skilled professionals and the need for continuous technological advancements pose challenges to the market players.
In conclusion, the market for drug delivery compositions is witnessing robust growth, driven by the increasing prevalence of chronic diseases, advancements in technology, and the focus on personalized medicine. With ongoing research and development activities, the market is expected to witness further advancements in drug delivery systems, leading to improved therapeutic outcomes and better patient care.
The University of Michigan invention works as follows
The present invention is a multicomponent composition and method of administering this composition that specifically translocates therapeutic molecules (e.g. drugs or prodrugs), across biological membranes. This reduces potential toxic side effects to nontargeted tissues and cells.
Background for Drug delivery compositions
There have been a number of attempts to administer therapeutic drugs to cancerous or precancerous cell in order to promote their apoptosis removal. These attempts have generally had limited success due to inadequacies with the delivery methods or agents themselves. Many anticancer agents lack the specificity needed to target only cancer cells. “Since most anticancer drugs strongly interfere with cell replication and other functions, nonspecifically delivering these agents to non-cancerous cells can lead to serious toxic effects.
The rapid clearance of these agents from the bloodstream makes it difficult to deliver them effectively. The administration of nucleic acids and peptides anticancer agents can also be difficult due to their immunogenicity and proteolytic degradation.
Also, many anticancer drugs have difficulty or are unable crossing the cell membrane of cancerous cellular. Hydrophobic molecules are small molecules (typically smaller than 1,000 Daltons), which allow for efficient delivery. Low molecular-weight cytotoxic drugs are more effective in locating in normal tissues than tumors. (K. Bosslet, Cancer Res. 58:1195-1201, 1998) This is due to high interstitial tension and poor blood flow in rapidly growing tumors. (R. K. Jain. J. Radiat. Biol. 60:85-100 (1991); R. K. Jain & L. T. Baxter Cancer Res. 48:7022-70332 (1998)). Anticancer agents that contain peptides and proteins are particularly limited in their ability enter cancer cells. Even agents capable of penetrating cancer cells tend to accumulate on the surface of the tumor tissue and do not penetrate the core of solid tumors.
The current drug delivery system (e.g. compositions) and anticancer drug systems are not up to the task. We need improved methods and systems that can deliver all therapeutic agents (e.g. hydrophilic, small, or macromolecular compounds), as well as translocate them. Hydrophobic, hydrophilic and small or macromolecular molecules are all examples of compounds that cannot enter target cells (e.g. cancerous tissues) without the use of improved drug delivery systems.
The present invention is a multicomponent composition and method of administering this composition that specifically translocates therapeutic molecules (e.g. drugs or prodrugs), across biological membranes. This reduces potential toxic side effects for non-targeted tissues and cells. The present invention, in certain embodiments, relates to multicomponent drug delivery compositions that contain a first component to target therapeutic agents to specific cells and tissue of interest, and a second to deliver (e.g. translocate a drug or a prodrug carried across a cell membrane) the agents. The present invention is suited to compositions that include a nanoparticle, such as superparamagnetic oxide nanoparticles, a cationic molecular (e.g. a protein-transduction domain), and a therapeutic agent.
In some embodiments the present invention provides compositions comprising a first component for targeting, wherein said first component comprises an anionic molecular having net negative charges, and a first component for drug delivery, wherein said first component includes a cationic molecular having a positive net charge and at least one therapeutic. In some embodiments, a positively charged cationic molecules associates with a negatively charged anionic molecules (e.g. electrostatic interaction). In other embodiments, the cationic molecules comprise a transduction protein domain. The present invention isn’t limited to any specific protein transduction domains. However, the preferred embodiments include TAT peptides or portions thereof. In some embodiments, TAT proteins comprise SEQ ID No:6. Other embodiments select the TAT peptides from SEQ ID Nos:1-5, 7-11. However, other sequences can be considered in other embodiments.
In some compositions the molecule recognition element binds to a biological target (e.g. cells or tissues that are of interest). The present invention contemplates a variety of molecule recognition elements, including but not limited to antibodies, nucleic acid, peptide signals, and the like.
The biological targets that are contemplated in the present invention, include but are not restricted to cell surface proteins (e.g., cancerous cells), cell surface receptors (e.g., cancerous), cell surface polysaccharides (e.g., cancerous cells), extracellular matrix protein, intracellular protein, intracellular nucleic acid, etc. The biological target may be located on the cell surface of a cancerous or diseased cell.
Certain embodiments of this invention provide compositions for drug delivery, in which the cationic molecules mediate the translocation into the targeted cell of the therapeutic agent. In certain embodiments, the hydrophilic molecule is used as a therapeutic agent. In some embodiments, the drug molecule (e.g. therapeutic agent) is a macromolecule. In certain embodiments, a therapeutic agent is an anticancer medication. In other embodiments, a cationic (e.g. TAT) molecule is attached to the therapeutic agent.
Certain compositions of the invention also contain anionic molecules. In certain embodiments, heparin is the anionic molecular.
In certain embodiments the drug delivery component comprises a carrier for a multivalent therapy agent. In certain embodiments, the multivalent therapeutic carrier is polyrotaxane.
The present invention also provides methods of delivering therapeutic agents into target cells. These include providing cells with surface-exposed biological targets, drug delivery compositions comprising a molecular identification element and an anionic molecular having a negative net charge; and a first component comprising a cationic molecular having a positive net charge; and at least one drug. In certain embodiments, a cationic component of the drug-delivery composition is responsible for the translocation of therapeutic agents into cells (e.g. cancer cells or diseased cells). Certain embodiments of compositions and methods used in the present invention are for treating cells and tissues inside a subject. Certain embodiments of compositions and methods in the present invention are capable of treating a variety of different subject types. In some embodiments the subjects may be mammals (e.g. humans). The present compositions are optimized for treating humans in preferred embodiments. However, the invention is not restricted to humans. The present invention includes effective compositions for drug delivery and treatment methods that can be used on a wide range of vertebrate species, including but not limited, to cows, pigs sheep, horses cats dogs rodents birds fish and the like.
In some preferred embodiments the cells or tissues being treated are resistant against one or more chemotherapy.
The present invention provides also methods for treating subjects with diseased cells, which include administering to the patient an effective amount using a drug-delivery composition. This composition includes: a targeting component comprising a molecular identification element and an anionic compound having a net negative charge; and a drug-delivery component consisting of a cationic. The therapeutic agent, a molecule with a net negative charge and a cationic molecule are combined in varying conditions to ensure that the cationic molecules facilitate the transfer of the therapeutic agents into the diseased cell.
In preferred embodiments of the invention, drug delivery compositions are provided (e.g. conjugates), which target and deliver therapeutic agents (e.g. anticancer) to targeted cells and tissues (e.g. cancer and tumor cells). In certain embodiments, the administration of present compositions can be used to treat (e.g. ameliorate) or stop (e.g. prophylaxis), disease states in a patient (e.g. cancer). In certain embodiments, gelonin is the drug that the compositions transport. In some embodiments, doxorubicin is the drug. In other embodiments the drug is gossypol (and its analogues and enantiomers as well as salts and bases), or a gossypolone. Additional embodiments of the present invention provide compositions and methods for targeting and delivering many other therapeutic molecule including, but not limited to: agents that induce apoptosis (e.g., Geranylgeraniol [3,7,11,15-tetramethyl-2,6,10,14-hexadecatraen-1-ol], pro-apoptotic Bcl-2 family proteins including Bax, Bak, Bid, and Bad); polynucleotides (e.g., DNA, RNA, ribozymes, RNAse, siRNAs, etc); polypeptides (e.g., enzymes); photodynamic compounds (e.g., Photofrin (II), ruthenium red compounds [e.g., Ru-diphenyl-phenanthroline and Tris(1-10-phenanthroline)ruthenium(II)chloride], tin ethyl etiopurpurin, protoporphyrin IX, chloroaluminum phthalocyanine, tetra(M-hydroxyphenyl)chlorin)); radiodynamic (i.e., scintillating) compounds (e.g., NaI-125, 2,5-diphenyloxazole (PPO); 2-(4-biphenyl)-6-phenylbenzoxazole; 2,5-bis-(5?-tert-butylbenzoxazoyl-[2? ])thiophene; 2-(4-t-butylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole; 1,6-diphenyl-1,3,5-hexatriene; trans-p,p?-diphenylstilbene; 2-(1-naphthyl)-5-phenyloxazole; 2-phenyl-5-(4-biphenylyl)-1,3,4-oxadiazole; p-terphenyl; and 1,1,4,4-tetraphenyl-1,3-butadiene); radioactive elements or compounds that emits gamma rays (e.g., 111In-oxine, 59Fe, 67Cu, 1251, 99Te (Technetium), and 14Cr); radioactive elements or compounds that emit beta particles (e.g., 32P, 3H, 35S, 14C,); drugs; biological mimetics; alkaloids; alkylating agents; antitumor antibiotics; antimetabolites; hormones; platinum compounds; monoclonal antibodies conjugated to anticancer drugs, toxins and/or defensins, radionuclides; biological response modifiers (e.g., interferons [e.g., IFN-?, etc], and interleukins [e.g., IL-2]); adoptive immunotherapy agents; hematopoietic growth factors; agents that induce tumor cell differentiation (e.g., all-trans-retinoic acid, etc); gene therapy reagents (e.g., antisense therapy reagents and nucleotides); tumor vaccines; and angiogenesis inhibitors and the like. “Those skilled in this art are aware that there are numerous other drugs and therapeutics agents suitable for delivery using the compositions of the invention.
The antifade agents or antioxidants include, but are not limited to, ascorbic acid, vitamins C and E, beta-carotene, its derivatives, other dietary antioxidants, phenylalanine, azide, p-phenylenediamine, npropylgallate, diazabicyclo[2,2,2]octane, and the commercial reagents SLOWFADE and PROLONG (Molecular Probes, Eugene Oreg Suitable antioxidants or antifade agents include, but are not limited to, ascorbic acid, vitamins C and E, beta-carotene and its derivitives and other dietary antioxidants, phenylalanine, azide, p-phenylenediamine, n-propylgallate, diazabicyclo[2,2,2]octane, and the commercial reagents SLOWFADE and PROLONG (Molecular Probes, Eugene Oreg.).
The anticancer agents are preferably agents that induce apoptosis, such as kinase-inhibitors (e.g. EGFR, VGFR, FGFR, PGFR, STI-571 and GLIVEC); antisense molecule; antibodies (e.g. HERCEPTIN, RITUXAN); cyclooxygenase-2 (
In some preferred embodiments of the invention, various compositions provide treatment for a variety of conditions, including but not limited, to breast cancers, prostate cancers, lung cancers, lymphomas and skin cancers. Other conditions include, but are not limited, to brain cancers, head and neck tumors, liver and bladder cancers, non-small lungs cancers, cervical cancers, leukemias, neuroblastomas and glioblastomas and T and B cells mediated autoimmune disease and the
The drug delivery compositions are designed to deliver anticancer agents to cancer cells, including but not limited: Altretamine, asparaginase, carboplatin, carmustine, cladribine, cisplatin, cytarabine, dactinomycin, etoposide, etoposide, VP-16, fludarabine, fluorouracil, 5-FU, gemcitabine, ifosfamide, irinote
In other embodiments, cancer cells are selected from a list of cells such as malignant melanoma, basal cell carcinoma, mammary, ductal, bowel, and deep tissue cancers (e.g. hepatocellular, CNS, primary lymphoma, and glioma).
The present invention provides a drug delivery composition that is optimized to deliver antiretroviral agents and/or drugs to cells which inhibit the growth and reproduction of HIV. Exemplary drugs and agents in this regard include, but are not limited to: nucleotide analogue reverse transcriptase inhibitors (e.g., tenofovir disoproxil fumarate [DF]); nucleoside analogue reverse transcriptase inhibitors (NRTIs) (e.g., zidovudine, lamivudine, abacavir, zalcitabine, didanosine, stavudine, zidovudine+lamivudine, and abacavir+zidovudine+lamivudine); non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g., nevirapine, delavirdine, and efavirenz); protease inhibitors (PIs) (e.g., saquinavir [SQV (HGC)], saquinavir [SQV (SGC)], ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir+ritonavir); and combinations thereof (e.g., highly active anti-retroviral therapy [HAART]).
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