Neuroblastoma treatment with taurolidine hydrolysis products

Abstract

To provide therapeutic methods and compositions for the treatment of neuroblastoma in juvenile mammals.SOLUTION: A method for treating neuroblastoma comprises a step for administering a composition to a patient, where the composition is composed of at least one from the group consisting of: taurinamide; taurultam; methylene glycol; taurultam and taurinamide in a ratio of 1 taurultam: 7 taurinamide; and taurultam, taurinamide and methylene glycol in a ratio of 1 taurultam: 7 taurinamide: 1 methylene glycol.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] REFERENCE TO PRIOR PENDING PATENT APPLICATIONS This patent application is (i) CorMedix Inc. and Robert DiLuc in connection with “THERAPEUTIC NANOPARTICLES FOR THE TREATMENT OF NEUROBLASTOMA AND OTHER CANCERS” (Docket No. CORMEDIX-14) This patent application is a continuation-in-part of pending prior U.S. patent application Ser. No. 15 / 403,876, filed Jan. 11, 2017, by CIO, entitled "NANOPARTICLE SYSTEM FOR THE TREATMENT OF NEUROBLASTOMA" (Docket No. CORMEDIX-14 PR This application claims the benefit of prior U.S. Provisional Patent Application No. 62 / 277,243, filed January 11, 2016 by CorMedix Inc. and Robert DiLuccio, relating to (OV); (ii) "NEUROBLASTOMA TREATMENT WITH TAUROLIDINE HYDROLYSIS" Regarding "CORMEDIX-33 PROV" (Reference No. CORMEDIX-33 PROV) This application claims the benefit of pending prior U.S. Provisional Patent Application No. 62 / 723,618, filed August 28, 2018 by medix Inc. and Bruce Reidenberg et al.

[0002] The three above mentioned patent applications are incorporated herein by reference. Technical Field The present invention relates generally to therapeutic methods and compositions, and more particularly to therapeutic methods and compositions for the treatment of neuroblastoma in the young mammalian body. [Background technology]

[0003] Neuroblastoma (NB) is the most common extracranial solid cancer of childhood and the most common cancer of early childhood. There are approximately 650 cases per year in the United States and 100 cases per year in the United Kingdom. Nearly half of neuroblastoma cases occur in children under the age of 2. Neuroblastoma is a neuroendocrine tumor that arises from neural crest elements of either the sympathetic nervous system (SNS). Neuroblastoma arises most frequently from one of the adrenal glands, but can also arise in neural tissue in the neck, chest, abdomen, or pelvis. It is important to note that although neuroblastoma arises from neural tissue, it is not a tumor of the central nervous system (CNS).

[0004] Neuroblastoma is one of the few human malignancies known to exhibit spontaneous regression from an anaplastic state to an entirely benign cellular appearance. Neuroblastoma is an extremely heterogeneous disease that is stratified into three risk categories: low-risk, intermediate-risk, and high-risk. Low-risk neuroblastoma is most commonly seen in infants and generally has a good outcome with observation alone or surgery, whereas high-risk neuroblastoma is less likely to be treated successfully even with the most intensive multimodality therapy available.

[0005] When neuroblastoma disease is localized, it is generally curable. However, long-term survival for children aged 18 months or older with advanced disease is poor despite aggressive multimodality therapy, including intensive chemotherapy, surgery, radiation therapy, stem cell transplantation, the differentiation agent isotrentinoin (also called 13-cis-retinoic acid), and frequent immunotherapy with anti-GD2 monoclonal antibody therapy.

[0006] Biological and genetic characteristics have been identified that, when added to classical clinical staging, allow for the allocation of patients to risk groups for planning treatment intensity. These criteria include the patient's age, extent of disease spread, microscopic appearance, and genetic features including DNA ploidy and N-myc oncogene amplification (N-myc regulates microRNAs). These criteria are used to classify neuroblastoma into low-, intermediate-, and high-risk disease. A recent biological study (COG ANBL00B1) analyzed 2,687 patients with neuroblastoma and a spectrum of risk assignments was determined. 37% of neuroblastoma cases are low risk, 18% of neuroblastoma cases are intermediate risk, and 45% of neuroblastoma cases are high risk. It should be noted that there is some evidence that high- and low-risk types of neuroblastoma are due to different mechanisms and not simply two different degrees of expression of the same mechanism.

[0007] Therapies for these different risk categories are quite different. Low-risk neuroblastoma can often be observed without any treatment or can be cured with surgery alone.

[0008] Intermediate-risk neuroblastoma is generally treated with surgery and chemotherapy. High-risk neuroblastoma is commonly treated with intensive chemotherapy, surgery, radiation therapy, bone marrow / hematopoietic stem cell transplantation, biologic-based therapy with 13-cis-retinoic acid (isotretinoin or Accutane), and antibody therapy (usually administered with the cytokines GM-CSF and IL-2).

[0009] With current treatments, patients with low-risk and intermediate-risk neuroblastoma have an excellent prognosis, with cure rates exceeding 90% for low-risk neuroblastoma and 70-90% for intermediate-risk neuroblastoma. In contrast, therapy for high-risk neuroblastoma over the past 20 years has resulted in cure rates of only about 30%. With the addition of antibody therapy, survival rates for high-risk neuroblastoma have increased significantly. In March 2009, a Children's Oncology Study Group study of 226 high-risk neuroblastoma patients showed that An early analysis of the Clinical Oncology Group (COG) trial showed that 2 years after stem cell transplant, 66% of those randomized to receive the chl4.18 antibody with GM-CSF and IL-2 were alive and disease-free, compared with only 46% of those who did not receive the antibody. Randomization was halted so that all patients enrolled in the trial could receive the antibody therapy.

[0010] Chemotherapeutic agents used in combination have been found to be effective against neuroblastoma. Commonly used agents for induction and stem cell transplant conditioning are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan, topoisomerase II inhibitors) and vinca alkaloids (vincristine). Some newer regimens include topoisomerase I inhibitors (topotecan and irinotecan) in induction and have been found to be effective against recurrent disease. Summary of the Invention [Problem to be solved by the invention]

[0011] However, there is a need for new methods and compositions that are effective against neuroblastoma. [Means for solving the problem]

[0012] According to the present invention, selected hydrolysis products of taurolidine are useful in treating neuroblastoma. Selected hydrolysis products of taurolidine are used in: Taurinamide; Taurultum; Methylene glycol; Taurultam and taurinamide in a ratio of 1:7 taurultam:taurinamide; and Taurultam, taurinamide and methylene glycol in a 1:7:1 ratio of taurultam:taurinamide:methylene glycol may include at least one from the group consisting of:

[0013] Taurinamide is given at a dosage range of 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 60 mg / kg, once daily to once weekly for an effective period based on individual patient response.

[0014] Taurultam is given in a dosage range of 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 60 mg / kg, once daily to once weekly for an effective period based on individual patient response.

[0015] Methylene glycol is given at a dosage range of 2.5 mg / kg to 160 mg / kg, with an optimal range of 2.5 mg / kg to 30 mg / kg, once daily to once weekly for an effective period based on individual patient response.

[0016] Taurultam and taurinamide (1:7 ratio of taurultam:taurinamide) is given once daily to once weekly for an effective period based on individual patient response, in a dosage range of taurultam 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 40 mg / kg, in combination with taurinamide 5 mg / kg to 280 mg / kg, with an optimal range of 35 mg / kg to 40 mg / kg.

[0017] Taurultam, taurinamide and methylene glycol (1:7:1 ratio of taurultam:taurinamide:methylene glycol) is given once daily to once weekly for an effective period based on individual patient response, with taurultam in a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg, in combination with taurinamide in a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 35 mg / kg to 40 mg / kg, and with methylene glycol in a dosage range of 2.5 mg / kg to 160 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg.

[0018] In one preferred form of the invention, the selected hydrolysate (i.e., the active ingredient) may be delivered systemically in a "shielded form" so that it can reach the site of the neuroblastoma without premature degradation.

[0019] More specifically, in one preferred form of the invention, the hydrolysates may be delivered in the form of nanoparticles, which comprise a core of the hydrolysates and an outer coating configured to prevent premature exposure of the hydrolysates before the nanoparticles arrive at the tumor site. The outer coating degrades as the nanoparticles move from the insertion site to the tumor site, so as to release the hydrolysates intact at the tumor site. In one preferred form of the invention, the coating comprises an absorbable polymer or lipid that degrades as the nanoparticles move from the insertion site to the tumor site.

[0020] In another aspect of the invention, the hydrolysates may be delivered using polymer systems configured to slow the degradation of the active ingredient. The degradation products may be "pegylated" using polyethylene glycol (PEG) to retard premature degradation of the active ingredient.

[0021] Selected hydrolysis products of taurolidine are given systemically, either as single agents or in combination with other oncolytic agents and / or radiation therapy. It is possible.

[0022] These and other objects and features of the present invention will be more fully disclosed or made apparent by the following detailed description of preferred embodiments of the invention which should be considered in conjunction with the accompanying drawings in which like numerals refer to like parts and in which: [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 is a graph showing that leukemia cell lines appear to be more sensitive to the effects of Taurolidine compared to healthy lymphocytes in vitro (but not in vivo). [Diagram 2] FIG. 2 is a graph showing that neuroblastoma cell lines are more sensitive to loss of viability by Taurolidine when compared to healthy fibroblasts in vitro (but not in vivo) (graph BJ). [Diagram 3] FIG. 3 is a graph or photograph showing that Taurolidine given to CB57 SCID mice bearing measurable tumors derived from a neuroblastoma cell line implanted subcutaneously in the CB57 SCID mice has efficacy in IMR5 tumors in vivo (but not in vitro), and measurable efficacy in SK-N-AS tumors. [Figure 4] FIG. 4 is a graph or photograph showing that Taurolidine given to CB57 SCID mice bearing measurable tumors derived from a neuroblastoma cell line implanted subcutaneously in the CB57 SCID mice has efficacy in IMR5 tumors in vivo (but not in vitro), and measurable efficacy in SK-N-AS tumors. [Diagram 5]FIG. 5 is a graph or photograph showing that Taurolidine given to CB57 SCID mice bearing measurable tumors derived from a neuroblastoma cell line implanted subcutaneously in the CB57 SCID mice has efficacy in IMR5 tumors in vivo (but not in vitro), and measurable efficacy in SK-N-AS tumors. [Figure 6] FIG. 6 is a graph or photograph showing that Taurolidine given to CB57 SCID mice bearing measurable tumors derived from a neuroblastoma cell line implanted subcutaneously in the CB57 SCID mice has efficacy in IMR5 tumors in vivo (but not in vitro), and measurable efficacy in SK-N-AS tumors. [Figure 7] FIG. 7 is a graph showing that when Taurolidine was administered to treat mice bearing a different cell line (SK-N-AS), also derived from neuroblastoma, a statistically significant reduction in tumor size was achieved, but overall survival was not significantly different from controls. [Figure 8] FIG. 8 is a graph showing that when Taurolidine was administered to treat mice bearing a different cell line (SK-N-AS), also derived from neuroblastoma, a statistically significant reduction in tumor size was achieved, but overall survival was not significantly different from controls. [Figure 9] FIG. 9 illustrates the mechanism of hydrolysis of Taurolidine. [Figure 10] FIG. 10 is a table showing the mean pharmacokinetic parameters of taurinamide. [Figure 11] FIG. 11 is a table showing the mean pharmacokinetic parameters of taurultam. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Taurolidine is a well-known antibacterial agent with a published mechanism of action and antibacterial spectrum. Taurolidine is unstable in the circulation and therefore has not been successfully developed for systemic infections. Taurolidine is used topically for peritonitis and as a catheter lock solution. When injected, it has shown efficacy in preventing infection.

[0025] Taurolidine has been recently studied for its oncolytic activity and has been found to have inhibitory effects on cultured cell lines in combination with standard chemotherapy or alone. Despite claims that in vitro inhibitory concentrations are clinically achievable, the only published human pharmacokinetic study showed no measurable concentrations of Taurolidine in healthy volunteers when 5 grams of Taurolidine was administered intravenously via a 20-minute infusion. This is believed to be due to the rapid hydrolysis of Taurolidine when administered systemically to the mammalian body.

[0026] It has been found that compared to healthy lymphocytes in vitro (but not in vivo), leukemia cell lines appear to be more sensitive to the effects of Taurolidine. See Figure 1.

[0027] Neuroblastoma cell lines have also been found to be more sensitive to loss of viability by Taurolidine when compared to healthy fibroblasts in vitro (but not in vivo), see Figure 2.

[0028] Furthermore, Taurolidine given to CB57 SCID mice bearing measurable tumors derived from neuroblastoma cell lines implanted subcutaneously in the CB57 SCID mice demonstrated efficacy in IMR5 tumors in vivo (but not in vitro), and measurable efficacy in SK-N-AS tumors (see Figures 3-6).

[0029] Note that in vitro potency against neuroblastoma cell lines is seen at the two highest concentrations tested, i.e., greater than 40 micromolar [1 mole / liter x 284 gm / mol x 1 mole / 1,000,000 micromolar x 40 micromolar x 1000 mg / gram = 11 mg / liter = 11 mcg / mL], as seen in Figure 2 (only the neuroepithelioma cell line, SK-N-MC cell line, has lower than 50% cell viability). IC50 values ​​are 80-140 micromolar for neuroblastoma cell lines and 200 micromolar for normal fibroblasts (see Figure 2).

[0030] Despite the relatively high IC50 of IRM5 in vitro (Figure 2), the observed efficacy of taurolidine treatment of IMR5 cell transplants in vivo (Figures 3-6) supports the conclusion that hydrolysis products of taurolidine may have independent antitumor activity. In other words, taurolidine treatment of neuroblastoma cells in vivo appears to be significantly more effective than taurolidine treatment of neuroblastoma cells in vitro. Since taurolidine is known to be metabolized to taurolidine hydrolysis products in vivo, this would support the conclusion that hydrolysis products of taurolidine may have significant antitumor activity against neuroblastoma cells. In fact, it may turn out that hydrolysis products of taurolidine have higher potency against neuroblastoma cells than unhydrolyzed taurolidine.

[0031] A statistically significant reduction in tumor size was achieved when Taurolidine was administered to treat mice bearing a different cell line (SK-N-AS) also derived from neuroblastoma, but the overall survival of the tumor-implanted mice was not statistically different from controls. See Figures 7 and 8.

[0032] It has now been discovered that selected hydrolysis products of taurolidine can be used to treat neuroblastoma. The mechanism of hydrolysis of taurolidine is shown in Figure 9. Selected hydrolysis products of taurolidine that can be used to treat neuroblastoma are: Taurinamide; Taurultum; Methylene glycol; Taurultam and taurinamide in a ratio of 1:7 taurultam:taurinamide; and Taurultam, taurinamide and methylene glycol in a 1:7:1 ratio of taurultam:taurinamide:methylene glycol may include at least one from the group consisting of:

[0033] Taurinamide is given at a dose range of 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 60 mg / kg, once daily to once weekly for an effective period based on individual patient response. Mean pharmacokinetic parameters for taurinamide are shown in Figure 10.

[0034] Taurultam is given at a dose range of 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 60 mg / kg, once daily to once weekly for an effective period based on individual patient response. Mean pharmacokinetic parameters for Taurultam are shown in Figure 11.

[0035] Methylene glycol is given at a dosage range of 2.5 mg / kg to 160 mg / kg, with an optimal range of 2.5 mg / kg to 30 mg / kg, once daily to once weekly for an effective period based on individual patient response.

[0036] Taurultam and taurinamide (1:7 ratio of taurultam:taurinamide) is given once daily to once weekly for an effective period based on individual patient response, in a dosage range of taurultam 5 mg / kg to 280 mg / kg, with an optimal range of 5 mg / kg to 40 mg / kg, in combination with taurinamide 5 mg / kg to 280 mg / kg, with an optimal range of 35 mg / kg to 40 mg / kg.

[0037] Taurultam, taurinamide and methylene glycol (1:7:1 ratio of taurultam:taurinamide:methylene glycol) is given once daily to once weekly for an effective period based on individual patient response, with taurultam in a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg, in combination with taurinamide in a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 35 mg / kg to 40 mg / kg, and with methylene glycol in a dosage range of 2.5 mg / kg to 160 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg.

[0038] The dose selection of hydrolysates was calculated as follows: AUC 0-inf taurultam / AUC 0-inf taurinamide = 42.9 / 312.7 =0.14 The use of weight-based AUC does not need to be corrected because the molecular weight difference is only one methyl group. Thus, the target ratio when taurultam and taurinamide are given in combination is 0.14 or 1:7. And the target ratio when taurultam and taurinamide and methylene glycol are given in combination is 1:7:1.

[0039] An effective dosage is a compound of the formula: [Human equivalent dose = mouse mg / kg dose x 1 adult / 12 mouse x 25 pediatric BSA ratio / 37 adult BSA ratio = pediatric dose mg / kg (https: / / www.fda.gov / downloads / drugs / gui dances / ucm078932.pdf) The human equivalent dose was calculated from the effective mouse dose using the formula:

[0040] In one preferred form of the invention, the selected hydrolysis products (active ingredients) are delivered systemically in a "shielded form" so that they can reach the site of neuroblastoma and avoid premature degradation.

[0041] More specifically, in one preferred form of the invention, the hydrolysate may be delivered in the form of nanoparticles, the nanoparticles comprising a core of hydrolysate and an outer coating configured to prevent premature exposure of the hydrolysate before the nanoparticles arrive at the tumor site. The outer coating degrades as the nanoparticles move from the insertion site to the tumor site, so as to release the hydrolysate intact at the tumor site. In one preferred form of the invention, the coating comprises an absorbent polymer or lipid that degrades as the nanoparticles move from the insertion site to the tumor site. By way of example and not of limitation, the coating can be made from a combination of copolymers and multimers derived from polymers constructed from l-lactide, glycolide, e-caprolactone, p-dioxanone, and trimethylene carbonate. The coating may also be combined with a glycol, such as polyethylene glycol (PEG), which may be either linear or branched.

[0042] If desired, the nanoparticles may include an excipient (eg, a buffer to enhance the hydrolytic stability of hydrolysis products within the nanoparticles). Furthermore, if desired, the nanoparticles can further comprise a coating that is configured to target the nanoparticles to the site of neuroblastoma, so as to improve the efficacy of hydrolysis products for the treatment of neuroblastoma.In one preferred form of the present invention, the coating comprises a binding molecule that is configured to target the delivery of the nanoparticles to a specific tissue.By way of example and not of limitation, the coating of the nanoparticles comprises a monoclonal antibody against N-type calcium channel (e.g., anti-N-type calcium channel extracellular surface Fab fragment) to bind the nanoparticles to neural tissue (e.g., neuroblastoma tumor).

[0043] In another aspect of the invention, the hydrolysates may be delivered using polymer systems configured to retard the degradation of the active ingredient and / or optimize the release profile of the active ingredient. By way of non-limiting example, the hydrolysates may be "pegylated" using polyethylene glycol (PEG) to retard premature degradation of the active ingredient and / or optimize the release profile of the active ingredient.

[0044] Selected hydrolysis products of taurolidine can be given systemically, either as a single agent or in combination with other oncolytic agents and / or radiation therapy.Examples of oncolytic agents that can be combined with hydrolysis products of taurolidine for systemic delivery are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan, topoisomerase II inhibitors), vinca alkaloids (vincristine), and topoisomerase I inhibitors (topotecan and irinotecan).

[0045] change While the present invention has been described in terms of certain exemplary preferred embodiments, those skilled in the art will readily understand and appreciate that the invention is not so limited and that many additions, deletions and modifications can be made to the preferred embodiments discussed above within the scope of the present invention.

Claims

1. 1. A method of treating neuroblastoma, comprising: Taurinamide; Taurultum; Methylene glycol; Taurultam and taurinamide in a ratio of taurultam:taurinamide of 1:7; and Taurultam, taurinamide and methylene glycol in a ratio of 1:7:1 taurultam:taurinamide:methylene glycol Administering to a patient at least one composition consisting of the group consisting of:

2. 2. The method of claim 1, wherein the composition consists of taurinamide.

3. 3. The method of claim 2, wherein the dose range is 5 mg / kg to 280 mg / kg once daily to once weekly for an effective period based on individual patient response.

4. 4. The method of claim 3, wherein the dosage range is from once daily to once weekly, optimally 5 mg / kg to 60 mg / kg, for an effective period based on individual patient response.

5. The method of claim 2, wherein the composition is administered in combination with an oncolytic agent and / or radiation therapy.

6. 2. The method of claim 1, wherein the composition consists of taurultam.

7. 7. The method of claim 6, wherein the dose range is 5 mg / kg to 280 mg / kg once daily to once weekly for an effective period based on individual patient response.

8. 8. The method of claim 7, wherein the dosage range is from once daily to once weekly, optimally 5 mg / kg to 60 mg / kg, for an effective period based on individual patient response.

9. The method of claim 6, wherein the composition is administered in combination with an oncolytic agent and / or radiation therapy.

10. The method of claim 1 , wherein the composition consists of methylene glycol.

11. 11. The method of claim 10, wherein the dose range is 2.5 mg / kg to 160 mg / kg once daily to once weekly for an effective period based on individual patient response.

12. 12. The method of claim 11, wherein the dosage range is from once daily to once weekly, optimally 2.5 mg / kg to 30 mg / kg, for an effective period based on individual patient response.

13. The method of claim 10, wherein the composition is administered in combination with an oncolytic agent and / or radiation therapy.

14. 2. The method of claim 1, wherein the composition consists of taurultam and taurinamide in a ratio of taurultam:taurinamide of 1:

7.

15. Taurultam and taurinamide (ratio of taurultam:taurinamide: 1:7) 15. The method of claim 14, in a dosage range of taurultam 5 mg / kg to 280 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg, in combination with taurinamide 5 mg / kg to 280 mg / kg, with an optimum range of 35 mg / kg to 40 mg / kg, given once daily to once weekly for an effective period based on individual patient response.

16. 15. The method of claim 14, wherein the composition is administered in combination with an oncolytic agent and / or radiation therapy.

17. 2. The method of claim 1, wherein the composition consists of taurultam, taurinamide and methylene glycol in a ratio of taurultam:taurinamide:methylene glycol of 1:7:

1.

18. 18. The method of claim 17, wherein taurultam, taurinamide and methylene glycol (1:7:1 ratio of taurultam:taurinamide:methylene glycol) is administered in a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg, in combination with taurinamide at a dosage range of 5 mg / kg to 280 mg / kg, with an optimum range of 35 mg / kg to 40 mg / kg, and in combination with methylene glycol at a dosage range of 2.5 mg / kg to 160 mg / kg, with an optimum range of 5 mg / kg to 40 mg / kg, given once daily to once weekly for an effective period based on individual patient response.

19. 18. The method of claim 17, wherein the composition is administered in combination with an oncolytic agent and / or radiation therapy.

20. 10. The method of claim 1, wherein the composition is delivered to the patient using one from the group consisting of parenteral delivery, intramuscular delivery, and intravenous delivery.

21. 10. The method of claim 1, wherein the composition is contained in nanoparticles, and the nanoparticles are further configured to delay hydrolysis of the composition until the nanoparticles reach a tumor site.

22. 22. The method of claim 21, wherein the nanoparticle comprises a core of the composition and an outer coating, the outer coating configured to prevent exposure of the composition prior to the nanoparticle reaching a tumor site.

23. 23. The method of claim 22, wherein the outer coating comprises an absorbable polymer or lipid that degrades as the nanoparticles migrate from the insertion site to the tumor site.

24. The method of claim 1 , wherein the composition is delivered using a polymer system configured to retard hydrolysis of the composition.

25. 25. The method of claim 24, wherein the composition is "pegylated" using polyethylene glycol (PEG) to retard premature hydrolysis of the composition.

26. 2. The method of claim 1, wherein the composition comprises at least two from the group consisting of taurinamide, taurultam and methylene glycol.

27. 2. The method of claim 1, wherein the composition comprises all three from the group consisting of taurinamide, taurultam and methylene glycol.

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