Vivo drug development and delivery systems and methods

The present disclosure generally pertains to in vivo drug development and delivery systems and methods. The systems include a hollow tubular assembly with a chamber for receiving and transmitting an ionizing substrate solution, and a structure to transmit non-radioactive ionizing radiation to the ionizing substrate solution. The resulting free radical drug is transferred directly into a patient treatment site through an applicator. The systems and methods described herein provide simple, inexpensive techniques for in vivo production of an optimal chemotherapeutic drug without the use of radioactive radiation and directly injecting the drug into the patient's tissue with very minimal systemic side-effects.

RELATED ART

Cancer is an insidious and complex disease requiring multiple modality options. The three prevailing treatment options include surgery, chemotherapy, and nuclear or radioactive radiation. Surgical procedures, such as debulking, remove a portion of a malignant tumor, but it is often difficult to eliminate all of the diseased tissue such that the tumor returns. Radiotherapy includes irradiation, radiation therapy, or radiation oncology and is defined as the use of ionizing radioactive radiation to treat disease, kill cancer cells, or shrink tumors. Chemotherapy is the use of chemicals to treat disease, which is not limited to cancer. All three procedures have advantages as well as serious systemic consequences. There are many different types of cancers, as well as other diseases, each requiring individual treatment options utilizing a combination of the above-described therapies.

Many cancer patients receive at least one form of radiotherapy during their treatment cycle. Traditionally, radiotherapy is conducted in specialized facilities at a significant cost, sometimes on the order of hundreds of thousands of dollars per patient. Ionizing radiation is produced when a particle, such as a photon, acquires enough energy to remove an electron from an atom or molecule. Ionizing radiation is a biological and environmental hazard. Direct ionizing radiation describes charged particles (electrons, protons, and alpha particles) with sufficient energy to produce ionization by collision. Indirect ionizing radiation generally refers to the use of uncharged particles (neutrons and photons) to liberate particles by direct ionization. Radiotherapy generally involves the use of indirect radiation for the generation of free radicals, such as hydroxyl radicals, which then damage cancerous or diseased cells.

The energy level of an electromagnetic particle is indirectly proportional to its wavelength. For example, gamma rays with wavelengths of 50 fm have an energy level of about 25 MeV; x-rays with 50 pm wavelength yield about 25 keV; ultraviolet light with a wavelength of 100 nm yields about 12 eV; visible light with a wavelength of 550 nm yields about 2 eV; and microwaves with 1 cm wavelength exhibit roughly 120 μeV.

One major obstacle in the treatment of aggressive cancers is the fact that these cancers require chemotherapeutic or radiotherapeutic doses that are harmful or fatal to the patient. Treatment of cancer is systemic, where the cytotoxic drugs or radiation attack both malignant cells and healthy tissues. Selectively targeting the diseased cells is very difficult. In addition, radiation or chemotherapy treatment suppresses the immune system and therefore makes the patient susceptible to a host of other diseases. An additional complication is the fact that the patient's body adapts to the treatment and becomes resistant to further therapy.

Glioblastoma multiforme (GBM) tumors are the most common and aggressive malignant brain tumors in humans and are classified by the World Health Organization (WHO) as Grade IV tumors. Most GBM tumors originate in the deep white matter of the brain and quickly infiltrate other areas of the brain and the body. GBM tumors may grow very large before symptoms become apparent. GBM tumors are one of the most aggressive, resulting in a typical survival rate of less than a year after diagnosis. Treatment of these types of tumors is generally palliative, i.e., focusing on relieving and preventing the suffering of the patient, as there is no cure currently available. Recurrent tumors usually occur within 2 cm of the original tumor post treatment, which generally involves surgery followed by radiation and chemotherapy. GBM tumors are very resistant to chemotherapy. Aggressive radiation or chemotherapy treatment of recurrent tumors is difficult because the health of the patient is compromised and further procedures will shorten survival time. Patients suffering from GBM tumors and other cancers, such as pancreatic cancer, typically have poor prognosis as the available treatment options become too toxic and ineffective for continued treatment.

What is needed in the art, therefore, is a targeted, localized, minimally invasive cancer treatment which is readily available, causes fewer side effects for the patient and can be periodically repeated as needed to prevent the reoccurrence of the cancer.

DETAILED DESCRIPTION

The present disclosure generally pertains to systems and methods for in vivo production of free radicals from a solution for the treatment of certain medical conditions. In one embodiment, hydroxyl radicals are produced from inexpensive medical grade hydrogen peroxide. The systems and methods allow for the targeted, localized, minimally invasive treatment of a variety of medical ailments. In addition, the described methods utilize an inexpensive process which can significantly affect the survival rates and survival times for those who suffer from a variety of diseases where conventional treatments are ineffective.

Unstable particles, such as gamma or x-rays, are classified as radioactive because they exhibit excess energy, mass, or both. To reach stability they must give off or emit the excess energy or mass. One embodiment of the present disclosure utilizes non-radioactive ultraviolet electromagnetic radiation (photons).

One embodiment of the present disclosure utilizes free radicals which are unstable atoms, ions, or molecules containing unpaired electrons. Biological systems produce radicals, which are used to kill invading pathogens and mutant cells. This action is defined as the reactive oxygen species (ROS). Antioxidants, such as vitamin C and vitamin E, act to counteract free radical damage in the body. ROS also form as a by-product of metabolism. Free radicals include atoms, molecules, or ions with unpaired valence electrons or open electron shells. One embodiment of the present disclosure utilizes the radical form of the hydroxyl molecule. The hydroxyl molecule exists in two forms: the hydroxide ion (OH−) and hydroxyl radical (OH.).FIG. 1illustrates the two forms of the hydroxyl molecule. While hydroxide is an ion with a negative charge (anion), the hydroxyl radical is charge neutral. Hydroxyl radicals exhibit extremely fast reaction rates and kinetics. The in vivo half-life is roughly one billionth of a second.

In one embodiment, the present systems and methods utilize the production of hydroxyl radicals (OH.) generated from hydrogen peroxide (H2O2) via exposure to subtype C ultraviolet light. Generation of the radicals may be accomplished through the use ultraviolet electromagnetic radiation subtype C (UVC) with a wavelength of approximately 220 nanometers (nm). This process is similar to one technique used in Advanced Oxidation Process (AOP), a chemical treatment process designed to kill or destroy organic materials in water and waste water by oxidation through reactions with hydroxyl radicals. UVC is a non-radioactive type of ionizing radiation.FIG. 2illustrates process100generating two hydroxyl radicals260(OH.) from a single molecule of an ionizable substrate solution210(H2O2molecule) in chemical reaction290after exposure to UVC ionizing radiation180. UVC radiation source240generates the predetermined UVC ionizing radiation180with a wavelength of roughly 220 nm. Note that substances other than hydrogen peroxide may be used to produce hydroxyl radicals. As an example, hydroxyl radicals may be developed by irradiating water. However, high energy radiation is required to develop hydroxyl radicals from water.

FIGS. 3A-3Dillustrate an embodiment of in vivo drug development and delivery systems150and190of the present disclosure. System150includes a drug delivery device200with an outer cannula151surrounding an inner cannula152. As used herein, a cannula is a tube that can be inserted into the patient's body for the delivery or removal of fluids. The system190includes a cable-hose assembly220extending from the posterior end170of device200(FIG. 3D). In this embodiment, a fluid is pumped through cable-hose assembly220by the application of pressure, where it then travels into device200and is deposited in preparation chamber155for exposure to ionizing radiation180. The fluid is then deposited into treatment area280. Optionally, cable-hose assembly220could include an external vacuum or suction function for removal of fluids and materials (vacuum equipment not shown). Referring again toFIGS. 3A-3D, the posterior end170of device200includes ports for electrical connections and other devices (not shown) or connection areas for attachment to hoses (FIG. 3D). Anterior end172of device200makes contact with and enters the patient treatment area280for the production and application of the generated hydroxyl radicals, which chemically react (oxidization process) with the living tissue in treatment area280.

Outer cannula151, inner cannula152, radiation cable153, and applicator156define an inner chamber155within device200. Inner chamber155receives precise, metered doses of the solution containing an ionizable substrate. As used herein, an ionizable substrate solution is a fluid that contains molecules which are converted to a free radical upon exposure to ionizing radiation. In one embodiment, the solution containing an ionizable substrate is a hydrogen peroxide solution. The substrate solution in chamber155is exposed to ionizing radiation via radiation cable153, as will be described in greater detail below. In one embodiment, the transmitted ionizing radiation180is UVC radiation. Chamber155is positioned at the anterior end172of device200and acts as an ionizing radiation preparation chamber155for irradiation of precise, metered doses of ionizable substrate solution210. In the example illustrated inFIGS. 3A-3D, the radiation cable153for transmitting externally generated ionizing radiation180is an optical fiber. The radiation cable153transmits externally generated ionizing radiation180to inner chamber155. The radiation cable153extends from the posterior end170of device200and terminates at the ionizing radiation preparation chamber155. In this embodiment, a cable sheath154envelops radiation cable153to secure and protect the conductors. The radiation cable153directs the ionizable radiation180to the ionizing substrate solution210residing in chamber155.

Outer cannula151serves as a main structural element of device200and, in conjunction with the outer surface of inner cannula152, forms an optional vacuum-assisted suction cannula for extraction of materials or application of other solutions, as directed by a physician, at the patient treatment area280. In one embodiment, the size of outer cannula151is that of a #16 gauge needle and inner cannula152is typically the size of a #32 gauge needle, although other sizes are possible in other embodiments. Device200may be supplied in different lengths, typically ranging from about 6 to about 300 mm although any practical length may be fabricated to accommodate access to different areas of the patient's body.

Applicator156is positioned at the anterior end172of the device200(FIG. 3C). In one embodiment, applicator156is constructed from a rigid or semi-rigid material which will not react with the free radical solution. In one embodiment, applicator156is constructed from glass or ceramic, although other materials are possible. The material utilized to fabricate cannula151should exhibit sufficient strength and rigidity to allow device200to pierce the skin and tissue of the patient. In one embodiment, applicator156is constructed as a hollow tubular structure through which the produced free radical drug may travel.

Referring toFIGS. 3A-3D, the pressure control element230pumps a predetermined, precise, metered dose of ionizable substrate solution210into preparation chamber155. The radiation source240generates a predetermined wavelength of ionizing radiation (illustrated inFIG. 2). Radiation cable153(e.g., optical fiber) is positioned to transmit the ionization radiation to preparation chamber155where irradiation of the ionizable substrate solution210occurs. Irradiation of the ionizable substrate solution210in chamber155will produce a precise, metered dose of free radical drug260. Activation of the pump control element230will advance another precise, metered dose of ionizable substrate solution210into chamber155, thereby expelling the previously produced free radical drug260from chamber155via applicator156. As an example, the predetermined metered doses of solution210will be in the range of microliters (μl), thus the predetermined metered doses of drug260will also be in microliters. Individual doses of drug260, in the range of microliters will effectively treat an area in the range of tens to hundreds of mm3. This process will be repeated as necessary to achieve the desired treatment plan.

To ensure the effective localization of the treatment of diseased tissue and minimize damage to healthy tissue, external imaging apparatus270(FIG. 3D) may be used to guide the accurate placement of device200. In many cases, treatment area280will be larger than the area suitable for a metered dose of drug260. As a result, device200will be repositioned within the patient and additional amounts of drug260will be produced and applied repeatedly as needed to ensure accurate treatment of the designated treatment area280. In one embodiment, imaging apparatus270may be as simple as a portable ultrasonic imaging device. In an additional embodiment, outer cannula151incorporates an optional embedded marker157that allows use of complex external imaging apparatus270to ensure precision three dimensional placement of device200within treatment area280.

In one embodiment, applicator156, inner cannula152and optional cable sheath154are fabricated from a chemically-resistant material, for example glass. All components that contact the patient will be constructed from biologically compatible materials which will not cause adverse reactions inside the body. Device200may be discarded after use.

FIG. 4is a simplified flow diagram describing a method of one embodiment illustrated inFIGS. 3A-3Dof the present disclosure. The pre-procedure preparation process begins at step301. This procedure is similar in complexity to a needle biopsy so the treatment pre-procedure preparation with be similar to the equivalent needle biopsy preparation. As an example, a needle biopsy of the brain is more complex than a liver needle biopsy so treatment of a brain tumor will logically be more complicated than treating a liver tumor. This method can be used to treat any localized treatment area of the body where targeted tissue can be identified with external imaging technology or other technique. This procedure is not suitable for any area of the body where a needle biopsy is contraindicated such as the brain stem. The complexity of the treatment procedure will dictate the pre-procedure preparation. The size and location of the treatment area(s) will also determine the complexity of the procedure and degree of care needed to keep the patient comfortable. Similarly, the physician may administer antibiotics or other drugs to prevent medical complications as is standard operating practice during many needle biopsies. This method may be performed in standard out-patient surgical facilities and in some cases a physician's office or mobile care facility.

Referring again toFIG. 4, the physician guides the placement of device200(FIG. 3D) into the patient treatment area280at step302. Placement of device200may include the use of an external imaging apparatus270(FIG. 3D). The external imaging apparatus may be guided by the use optional embedded marker157for precise placement of device200. Device200is inserted into the patient's body to access treatment area280. The diameter of device200is on the order of a #16 gauge needle although other diameters are possible. A small diameter for device200is desirable to help ensure a minimally invasive procedure. In step303, pump apparatus230is activated to advance a precise, metered dose of ionizable substrate solution210from pump apparatus230to cable-hose assembly220for transfer to device200. A precise, metered dose of ionizable substrate solution210then advances to preparation chamber155. In this embodiment, the ionizable substrate solution210is a hydrogen peroxide solution (H2O2). In step304, radiation source240is activated and the ionizing radiation180travels through the cable-hose assembly220and radiation cable153to irradiate the ionizable substrate solution210in preparation chamber155. In this embodiment, the ionizing radiation is subtype C ultraviolet electromagnetic radiation (UVC) with a wavelength of roughly 220 nm. Radiation source240is a generator (e.g., lamp) capable of generating UVC electromagnetic radiation with wavelength of roughly 220 nm. In one embodiment, radiation cable153is an optical fiber capable of transmitting UVC radiation with a wavelength of roughly 220 nm. As illustrated inFIG. 2, exposing the ionizable substrate solution210to ionizing radiation180will cause a chemical reaction290that will produce two free radical drugs260from each molecule of ionizable substrate solution210. In this embodiment, two hydroxyl radicals (free radical drug260) are produced in chamber155from each molecule of hydrogen peroxide. In step305, the pump apparatus230is activated, expelling the free radical drug260into the treatment area280via applicator156. The volume of the dispensed free radical drug260is generally in the range of microliters, although any practical quantity may be produced. At the same time, activation of the pump apparatus230, in step,305also advances the next precise, metered dose of ionizable substrate solution210into chamber155. In step306, the physician determines if additional volumes of the free radical drug260are desired. If more free radical drug is desired, steps303through305may be repeated to generate additional doses to be dispensed into the patient treatment area280. The procedure advances to step307if the physician determines that an adequate amount of free radical drug260has been deposited into treatment area280. In step307, the physician can decide to repeat steps302-306as needed to achieve the overall treatment plan. Steps303to305typically treat an area in the range of tens to hundreds of cubic millimeters (mm3) based on doses in the range of microliters. Steps302-307allow the treatment of any practical-size treatment area280. The procedure terminates at step308and the post-procedure and post-care of the patient begins.

FIGS. 5A-5Billustrate an embodiment of a portable in vivo drug development and delivery systems160and250of the present disclosure. System160includes a drug development and delivery device200with an outer cannula161surrounding an inner cannula162. Device200functions exactly as described with reference to systems150and190. Systems160and250include a portable control device255connected to the posterior end174of device200(FIG. 5A). Pump control cartridge235and power pack245are replaceable cartridges connected to portable control device255. Pump control pack235contains sufficient quantities of ionizable substrate solution210to develop many doses of free radical drug260. Power pack245supplies sufficient power for extended operation of systems160and250. In this embodiment, a fluid is pumped from pump control pack235through portable control device255by the application of vacuum or pressure. The fluid then travels into device200and is deposited in preparation chamber165for exposure to ionizing radiation180. The fluid is then pumped into treatment area280. Optionally, systems160and190may include external vacuum or suction functions for removal of fluids and materials (vacuum equipment not shown). Anterior end175of device200makes contact with and enters the patient treatment area280for application of the generated hydroxyl radicals which chemically react (in an oxidization process) with the living tissue in treatment area280.

Referring toFIG. 5A, outer cannula161, inner cannula162, radiation cable169and applicator166define an inner chamber165in device200. Inner chamber165receives precise, metered doses of the ionizable substrate solution210. As used herein, an ionizable substrate solution210is a fluid that contains molecules which are converted to a free radical upon exposure to ionizing radiation. In one embodiment, the solution containing an ionizable substrate is a hydrogen peroxide solution.

The substrate solution in chamber165is exposed to ionizing radiation180via radiation cable169. In one embodiment, the transmitted ionizing radiation180is UVC radiation with wavelength of roughly 220 nm, although other wavelengths are possible in other embodiments. Chamber165is positioned at the anterior end175of device200and acts as an ionizing radiation preparation chamber165for irradiation of precise, metered doses of ionizable substrate solution210. In the example illustrated inFIGS. 5A-5B, the radiation cable169used to transmit the generated ionizing radiation180is an optical fiber. Radiation cable169transmits the generated ionizing radiation180to chamber165and extends from the posterior end174of device200terminating at the ionizing radiation preparation chamber165. In this embodiment, a cable sheath164envelops the radiation cable169to secure and protect the conductors. The optical fiber169directs the ionizable radiation180to the ionizing substrate solution210residing in chamber165.

Outer cannula161serves as a main structural element of device200and, in conjunction with the outer surface of inner cannula162, forms an optional vacuum-assisted suction cannula for extraction of materials or application of other solutions, as directed by a physician, at the patient treatment area280. In one embodiment, the size of outer cannula161is that of a #16 gauge needle and inner cannula162is typically the size of a #32 gauge needle, although other sizes are possible in other embodiments. Device200may be constructed in different lengths, typically ranging from about 6 to about 300 mm, although any practical length may be fabricated to accommodate access to different areas of the patient's body.

Applicator166is positioned at the anterior end175of device200(FIG. 5A). In one embodiment, applicator166is constructed from a rigid or semi-rigid material which will not react with the free radical solution. In one embodiment, applicator166is constructed from glass or ceramic, although other materials are possible. The material utilized to fabricate cannula161should exhibit sufficient strength and rigidity to allow device200to pierce the skin and tissue of the patient.

Referring toFIG. 5A, portable control device255includes electronic subassembly163, UVC LED168, and switch265(as well as ports for connection to device200), pump control apparatus235, and power pack245. Additionally, portable control device255may also include ports for connection to delivery device200. Device200is connected to the anterior end176of portable control device255, and pump control apparatus235and power pack245are connected to anterior end177of portable control device255. UVC LED168is mounted on electronic subassembly163. In this embodiment, UVC LED168is an LED capable of radiating UVC radiation at a wavelength of roughly 220 nm. Electronic subassembly163controls the operation of UVC LED168, switch265, and pump control apparatus235. Activation of switch265causes electronic subassembly163to advance a precise, metered dose of ionizable substrate solution210from pump control apparatus235through device200into preparation chamber165, while concurrently expelling the previously produced radical drug260in chamber165via applicator166. At the same time, electronic subassembly163powers LED168generating ionizing radiation180that travels via radiation cable169to irradiate the ionizable substrate solution210in chamber165, producing two molecules of radical drug260from each molecule of substrate solution. As an example, the predetermined metered doses of solution210will be in the range of microliters (μl), and therefore the predetermined metered doses of drug260will also be in the range of microliters. Individual doses of drug260, in the range of microliters, will effectively treat an area in the range of tens to hundreds of mm3. This process will be repeated as necessary to achieve the desired treatment plan.

To ensure the effective localization of the treatment in treatment area280and reduce damage to healthy tissue, external imaging apparatus270(FIG. 5B) may be used to guide the accurate placement of device200. In many cases, treatment area280will be larger than suitable for a metered dose of drug260so that device200will be repositioned and drug260will be produced and applied repeatedly as needed to ensure accurate treatment of the designated treatment area280. In one embodiment, imaging apparatus270may be as simple as a portable ultrasonic imaging device. In an additional embodiment, outer cannula161incorporates an optional embedded marker167that allows use of complex external imaging apparatus270to ensure precision three dimensional placement of device200within treatment area280. In one embodiment, applicator166, inner cannula162, and optional cable sheath164are fabricated from a chemically-resistant material, for example glass. Preferably, all components that may contact the patient will be constructed from biologically compatible materials which will not cause adverse reactions inside the body of the patient. Device200is normally discarded after use.

FIG. 6is a flow diagram describing the method of one embodiment illustrated inFIGS. 5A-5Bof the present disclosure. The pre-preparation process begins at step311. This method is similar in complexity to a needle biopsy so the pre-procedure preparation with be similar to the equivalent needle biopsy preparation. As an example, a needle biopsy of the brain is more complex than a liver needle biopsy so treatment of a brain tumor will logically be more complicated than treating a liver tumor. This method can be used to treat any localized treatment area of the body where targeted tissue can be identified with external imaging technology or other technique. This procedure is not suitable for any area of the body where a needle biopsy is contraindicated such as the brain stem. The complexity of the treatment procedure will dictate the pre-procedure preparation. The size and location of the treatment area(s) will also determine the complexity of the procedure and degree of care needed to keep the patient comfortable. Similarly, the physician may administer antibiotics or other drugs to prevent medical complications as is standard practice during a needle biopsy. This treatment method may be performed in standard out-patient surgical facilities or in some cases a physician's office or mobile care facility.

As outlined in step302, the physician guides the placement of device200(FIG. 5B) into the patient treatment area280. Placement of device200may include the use of an external imaging apparatus270(FIG. 5B), and as desired the external imaging apparatus may be guided by the use of optional embedded marker167for precise placement of device200. Device200is inserted into the patient's body to access treatment area280. The diameter of device200is on the order of a #16 gauge needle although other diameters are possible. A small diameter for device200is desired to help ensure that the procedure remains minimally invasive. In step313, pump apparatus235is activated by switch265to advance a precise, metered dose of ionizable substrate solution210from pump control apparatus235to portable control device255. The solution210is then transferred to device200. A precise, metered dose of ionizable solution210advances to preparation chamber165. In this embodiment, the ionizable substrate solution210is a hydrogen peroxide solution (H2O2). In step314, radiation source240(UVC LED168) is activated by switch265and the ionizing radiation180travels through the radiation cable169to irradiate the ionizable substrate solution210in preparation chamber165. In this embodiment, radiation source240is a UVC LED168capable of generating ionizing radiation180with a wavelength of roughly 220 nm, thus producing ionizing radiation180as subtype C ultraviolet electromagnetic radiation (UVC) with a wavelength of roughly 220 nm. In one embodiment, radiation cable169is an optical fiber capable of transmitting UVC radiation with a wavelength of roughly 220 nm. As illustrated inFIG. 2, exposing the ionizable substrate solution210to ionizing radiation180will cause a chemical reaction290that will produce two free radical drugs260from each molecule of ionizable substrate solution210. In this embodiment, two hydroxyl radicals (free radical drug260) are produced, in chamber165, from each molecule of (ionizable substrate solution210(hydrogen peroxide). In step315, the pump control apparatus235is activated by switch265, expelling the free radical drug260into the treatment area280via applicator166. In step315, a free radical drug260in the volume range of microliters is dispensed, although any practical volume may be produced. At the same time, activation of the pump apparatus235in step305also advances the next precise, metered dose of ionizable substrate solution210into chamber165. In step316, the physician determines whether additional doses of the free radical drug260are desired. If the production of additional free radical drug260is desired, the physician may repeat steps313through315to generate additional doses. Otherwise, the method advances to step317, where the physician may repeat steps312-316as desired to achieve the overall treatment plan. Steps313to315typically treat an area in the range of tens to hundreds of cubic millimeters (mm3) based on metered doses in the range of microliters. Steps312-317allow the treatment of any practical-size treatment area280. The procedure terminates at step318and the post-procedure and post-care of the patient begins.

The disclosed systems and methods allow for the production of a precise concentration and volume of a free radical drug solution which may immediately thereafter be injected into the treatment area. In one embodiment, the systems and methods produce a hydroxyl radical drug solution. In an additional embodiment, the treatment dose volume is in the range of several microliters, although any practical quantity can be produced and delivered by systems150,160,190and250.

The blood-brain-barrier (BBB) is a natural filter that prevents many undesired substances from reaching the brain. Many chemotherapy drugs are on the order of 200 to 1,200 Daltons and cannot pass to the brain without suppression of the BBB. Suppression of the BBB allows passage of solutes 10 to 100 times larger than normal. However, this process allows undesired solutes, proteins, and pathogens to pass. BBB suppression drugs also may cause dangerous swelling of the brain. One advantage of the methods described herein and the resulting locally in vivo produced hydroxyl radical is the patient's BBB is not a factor, thus simplifying treatment of diseases which affect the brain, such as GBM. The hydroxyl radical is 40% smaller than the smallest nanoparticle, with a diameter of roughly 400 pm, or 17 Daltons.

An additional advantage of the presently disclosed systems and methods is the ability to treat aggressive and advanced cancers after the exhaustion of other treatment options. For example, current GBM tumor therapy treatment cycles typically involve surgery, radiotherapy, and chemotherapy. Survival upon GBM tumor recurrence is typically less than six months as the patient's failing health prevents further treatment options. The presently disclosed systems and methods cause little or no adverse systemic effects while allowing frequent outpatient treatments as often as every few months, greatly extending patient survival time.

An added benefit of the described systems and methods is that unlike current chemotherapeutic treatment methodologies, the localized in vivo development of free radicals, for example hydroxyl radicals, causes very little or no systemic effects. The produced free radicals may be targeted directly at the diseased tissues with minimal impact to surrounding healthy tissues. In addition, the methods of generating and administering the free radicals are relatively simple when compared to conventional chemotherapy or radiotherapy techniques. Therefore, treatment may often be administered at a physician's office or mobile facilities. The infrastructure needed to support the presently described systems and methods is readily available. Surgeons and many physicians already possess the necessary skills to administer the therapy. Outpatient surgical care facilities already have access to the required external imaging equipment. This localized free radical treatment method is compatible with existing chemotherapy and radiotherapy techniques and may be used in conjunction with these methods. Diseased tissue cannot develop a tolerance to free radicals. Simple counter measures are available to prevent the free radicals from affecting surrounding healthy tissues, such as the use of antioxidants vitamins C and E. These methods and systems are very inexpensive as compared to conventional cancer treatment methods and have very low risks compared to these other options. Additional applications of the presently described systems and methods may include non-cancer therapies, for example cosmetic and surgical skin treatments.

Accordingly, the benefits of these disclosed systems and methods allow for localized treatment modalities capable of killing any identifiable diseased tissue. The complexity of these methods is on the order of the complexity of a needle biopsy. In many cases, the patient will have already undergone a needle biopsy to confirm the diagnosis of the disease. In some cases, a needle biopsy may be performed concurrently with the presently described methods.

The free radicals of the present disclosure are optimum chemotherapy drugs. Most free radicals, for instance hydroxyl radicals, are extremely chemically-reactive, making their production and use outside of the human body risky. Currently, delivery of hydroxyl radicals inside diseased tissue is accomplished only through the use of radioactive ionizing radiation. The production of free radicals via radiotherapy is well established and the pharmacology is clearly understood. However, radiotherapy exposes healthy and diseased tissue to the radioactive radiation with short- and long-term systemic consequences. The methods and systems described in the current disclosure provide for the in vivo development and delivery of free radicals directly to the patient's tissue without systemic affects or exposure to radioactive ionizing radiation.