Tag Archives: medication delivery

Chemotherapy Paste

Treating Melanoma with a “Chemotherapy Paste” for Better Tolerance

 According to the American Skin Cancer Foundation, melanoma is the most lethal form of cancer due to its capability of spreading from the skin to almost anywhere else in the body. For that reason, it has traditionally been necessary to take a very aggressive stance when treating skin cancers, using intravenous chemotherapy, radiation therapy, and surgery. For better tolerance and less crippling systemic side effects, scientists have developed a “chemotherapy paste” that can be applied directly to the skin to bypass the systemic treatment modality, and treat melanoma without the patient experiencing nausea and vomiting often associated with intravenous chemotherapy.

The culprits behind skin cancer are squamous cells, basal cells, and melanocytes. Melanocytes are the cells which are subject to becoming melanoma. They manufacture a brownish pigment called melanin, which imparts a tan or brown color to the skin, and protect deeper skin layers from harmful rays of the sun. When skin is exposed to the sun, melanocytes produce more melanin, which causes the skin to become darker.

Melanoma is a skin cancer which develops from melanocytes, and although it can develop anywhere on the skin surfaces, melanoma develops most commonly on the chest and on the back for men, whereas for women it most frequently develops on the legs. For both men and women, it can also develop on the face and neck. Melanoma occurs less frequently than either squamous cell cancers or basal cell cancers, but all three cells can be targets for skin cancer.

The skin is normally the first line of defense against any kind of harmful microbe or material, which would otherwise penetrate the body and wreak havoc. Unfortunately, this brilliant barrier also prevents useful drugs from being directly admitted onto the skin to treat skin diseases until recently.

A group of researchers developed a “chemotherapy paste” that incorporates nanoparticles called transfersomes to aid drug delivery through the skin to directly treat skin cancer. These transfersomes encase chemotherapy—in this case, paclitaxel—in a phospholipid bilayer-based surfactant that render the drug malleable to help penetrate the skin’s epidermal layers. A peptide was added to the transfersome complex to enhance its ability to infiltrate the skin and cancer cells and deliver paclitaxel directly to the tumor. To prolong the skin-penetrating effects, the “chemotherapy paste” was encased in a hydrogel medium to cover the “painted-on” site of the paste.

When the transfersome paste was applied to mice with melanoma, tumor sizes were reduced by half after 12 days compared to the set of mice that were receiving chemotherapy injections alone. However, it is still too early to see if the same results will transfer to humans, though a non-systemic “chemotherapy paste” approach to treating cancer will be a breakthrough that can vastly improve quality of life for cancer patients.

C. difficile Treatment

Utilizing Fecal Microbiota Treatment Modalities for C. difficile Treatment

An infection with Clostridium difficile, or C. difficile, is an unpleasant matter resulting in severe diarrhea and ultimately dehydration with its sequelae of electrolyte imbalances that has profound impacts on the heart and the nervous system. Most cases occur in hospitals, though it has been known to occur in the community within people who are typically immunocompromised.

A powerful new C. difficile treatment method has been pioneered by the University of Alberta, Canada, in which capsules containing bacteria from the fecal material of a healthy donor have been developed, intended for ingestion by a C. difficile patient, so as to help restore balance to the gut. The fecal microbiota transplant (FMT) procedure consists of feces from a healthy donor which have been filtered and processed until it contains only bacteria, and this filtered material is then encapsulated within a gel that breaks down easily in the recipient’s gut.

The human digestive and immune systems are host to literally hundreds of different kinds of gut bacteria, whose combined purpose is to assist with digestion and the body’s immune system. When someone becomes infected with any kind of harmful agent that requires the use of antibiotics, the normal healthy balance in the gut can be severely disrupted. This creates a window of opportunity for microorganisms such as Clostridium difficile to enter the picture and create havoc in the gut.

Patients who participated in the study declared that there was no unpleasant odor or taste associated with the capsules, because the transferred stool bacteria are encased in a gel included within the capsule. Not only are the capsules close to 100 percent effective, but they are far less invasive compared to a colonoscopy.

In addition to the less invasive nature of the treatment, the capsules are inexpensive, and does not involve any form of sedation for the person being treated. The capsules can also be administered in a doctor’s office, with no preparation necessary.

As a large percentage of people who have contracted C. difficile have been bothered by the recurrent nature of the disease, the recurrence factor seems to have been eliminated in participants who ingested FMT capsules as a form of C. difficile treatment. Once the gut of an FMT recipient has been restored to its normal healthy balance by the bacteria included in the capsules, recurrence is no longer an issue, and repeat treatments have not been necessary.

Many of the participants in the study experienced significant relief within just a few days of undergoing treatment. Since only a single treatment is needed to achieve success, with no ongoing treatments being necessary, there could hardly be a faster, more effective solution to the problem. To this point, no adverse reactions have been reported by patients and have been well tolerated thus far.

However, to achieve effective C. difficile treatment results, a fairly large number of capsules have to be ingested all within the space of an hour. In order for the desired effects to be achieved, it is necessary to deliver a high volume of healthy donor fecal material, and this must be accomplished by ingesting as many as 40 of the prepared capsules in a relatively short period of time—a small price to pay for relief.

Apart from transforming the way C. difficile treatments will be administered, it is expected that the capsule delivery method will entirely revolutionize the way FMT will be administered in the future, because of its ease of use, low cost, low impact on recipients, and extremely high rate of success.

Portable Vaccine Kit

Portable Vaccine Kits Can Be Transported to High-Risk Areas Without Power to Create On-the-Spot Vaccines by Just Adding Water

For vaccines to be effective, a continual chain of refrigeration is important to keep them viable. In areas where power sources are limited or nonexistent, such as developing nations, or in areas where elaborate medical equipment isn’t found for miles around, a portable vaccine kit could be the turning key to keeping an epidemic in check, thus saving many lives.

A team of researchers at Harvard’s Wyss Institute sought out to create a practical and mobile method to create medical treatments anywhere. A portable system was developed that enables the technician to produce an essential biomolecule as needed without requiring the aid of a refrigerator or a laboratory—instead, simply add water.

At the core of the scientists’ “portable biomolecular manufacturing kit” are two freeze-dried pellets that can be mixed and matched to create different compounds that cater to specific treatment modalities. Water is the only component needed to rehydrate and mix the ingredients. The pellets have a shelf life of at least a year, potentially longer.

The pellets come in two forms: reaction pellets and instruction pellets. The former contains no cells and genetic material and acts as the base that can be used to generate different drugs, whereas the instruction pellets contain DNA instructions to direct the reaction pellet and thus specifies the type of medication to produce. By combining the two pellets with water, a vast array of vaccines, antibacterial peptides, and antibody conjugates can be manufactured on the spot. Therapy from the rehydrated pellets can be administered orally, topically, or as injections to treat food poisoning, prevent wounds from getting infected, and dispense vaccines during a viral outbreak, such as influenza.

The portable vaccine kit is also an inexpensive biomolecular manufacturing kit at approximately three cents per microliter. Apart from its clinical use, researchers and students can use the kits for study purposes when state-of-the-art facilities and appliances are inaccessible.

Transdermal Ibuprofen Patch

Transdermal Ibuprofen Patch for Local Pain Relief

Ibuprofen is an over-the-counter nonsteroidal anti-inflammatory drug (NSAID) used widely for its analgesic, antipyretic, and, in higher doses, for its anti-inflammatory effects. NSAIDs are commonly used to treat everyday maladies, such as headaches, menstrual cramps, joint pain, and low-grade fever. NSAIDs in pill form are designed to work systemically, although pain and discomfort experienced by a person who uses this medication are typically isolated to one area. As a method of solving this conundrum, scientists at University of Warwick in England have developed the first transdermal ibuprofen patch that, when applied to the skin, can achieve local pain relief.

NSAIDs work by inhibiting cyclooxygenases (COX-1 and COX-2)—enzymes responsible for producing prostaglandins, which, in turn, promote inflammation, pain, and fever. COX-1, however, also produces prostaglandins that activate platelets and protect the stomach and intestinal lining from the stomach’s acidic environment. Due to the drug’s systemic effects, large doses and long-term use of NSAIDs can lead to gastrointestinal (GI) bleeding and ulcers.

With the help of the Bostik company, who custom-designed a flexible adhesive polymer, the transdermal ibuprofen patch can hold up to 30 percent ibuprofen by weight—compared to other drug-carrying patches and gels that contains 5-10 times less. There are ibuprofen-containing gels currently on the market, but they don’t hold as much of the drug as the patch and application is messy. Once on the skin, the patch delivers continuous and consistent levels of ibuprofen directly to the affected area for 12 hours, without passing through the bloodstream first. Once applied, the patch remains on the skin for 12 hours and easily peels off with no sticky residue, while causing no discomfort to wearer.

The scientists are currently testing the polymer for other types of medication for transdermal drug delivery that weren’t possible with traditional polymers. In the meantime, the transdermal ibuprofen patch is expected to be to be released by Medherant, an offshoot company of University of Warwick, in two years’ time.

New Nebulizer Device

New Nebulizer Device Better at Delivering Medications than Injections and Inhalers

Researchers at Royal Melbourne Institute of Technology (RMIT) have developed a new nebulizer device dubbed Respite engineered to deliver higher doses of medication into the lungs at a faster rate than traditional nebulizers, while fitting comfortably in the palm of one’s hand. Asthma, cystic fibrosis, diabetes, and lung cancer sufferers may greatly benefit from this new technology.

Utilizing several AA batteries, Respite works by producing surface acoustic waves—a specific form of sound wave that travels parallel to the surface of a material that exhibits elasticity—on a small microchip device measuring 2 cm by 1 cm. The sound waves agitate the liquid medicine resting in a compact drug vial and convert it into an aerosol, or mist, to be inhaled by patients through a mouthpiece at the end of the device. Current nebulizers deliver medication at 0.4 mL/minute, in which the fine mist that’s generated cannot be used to deliver insulin, protein, peptides, or DNA. On the other hand, Respite can deliver medication at a rate of up 3 mL/minute, with a resulting mist that’s thicker and heavier that can potentially aerosolize larger molecules and carry them directly into the lungs.

The research team tested Respite with monoclonal antibodies for lung cancer and stem cells for lung regeneration in hopes of developing a low-cost, cancer drug-delivery mechanism. Success came when they tested a DNA flu vaccine using the prototype on a sheep subject, which elicited comparable immune response as that of an injection. The scientists are also looking into nonmedical applications, such as cosmetics and surface and equipment sterilization.

As the new nebulizer device is made ready for market slated to be released sometime in the next five years, RMIT researchers are looking to streamline the device so that it uses less battery power and ultimately sell it for less than $50 US.

Microneedle-Covered Capsule

Promising Microneedle-Covered Capsule to Supersede Injections?

A swallowable microneedle-covered capsule—approximately 2 centimeters long and 1 centimeter in diameter—was devised by Massachusetts Institute of Technology (MIT) researchers, working with Massachusetts General Hospital (MGH), as a way to deliver medications orally and perhaps replace injections in the future.

The prototype pill is made of acrylic—serving as a medication reservoir—and encased with tiny hollow stainless steel needles (5 millimeters in length) that are designed to “inject” drugs directly into the stomach lining. Large medications, usually consisting of proteins, are not readily absorbable and thus degraded in the stomach and rendered useless before it can be absorbed. Insulin was tested in pigs using the microneedle-covered capsule technology and was found to lower blood glucose levels more effectively than subcutaneous insulin injections.

However, the capsule took longer than a week to go through the digestive tract and evidence of tissue damage was not apparent. The scientists also claim the gastrointestinal (GI) tract has no pain receptors so no discomfort is felt as the microneedle-covered capsule moves through the GI canal.

The new medication delivery mechanism may be better suited for injecting into the gut a class of drugs called biologics that include vaccines, recombinant DNA, RNA, and antibodies, such as those for autoimmune diseases like arthritis and Crohn’s disease that often require intravenous infusions to ensure effective drug delivery.  Nanoparticles and microparticles were originally engineered for oral medication delivery for biologics but they are expensive to manufacture and a new system has to be created for a different drug. With the microneedle-covered capsule, the researchers are aiming for a universal delivery system that can be reproduced for different drugs inexpensively.

To ensure absolute safety, the scientists are working on replacing the stainless steel needles with digestible polymers and sugar that would continue to release medication into the GI lining once it breaks off from the capsule and lodges itself into the gut as it decomposes.

Glaucoma More Bearable with Nanodiamond Contact Lenses

Scientists have long suspected the usefulness of nanodiamonds as mechanisms for targeted medication delivery due to their microscopic, safe nature—thanks to their carbon makeup—along with their unique tendency for fluorescence. UCLA School of Dentistry researchers from the Jane and Jerry Weintraub Center for Reconstructive Biotechnology have incorporated timolol maleate—a common eyedrop to help manage glaucoma—with nanodiamond contact lenses to regulate drug delivery to eyes and reduce side effects associated with eyedrops.

Glaucoma is characterized by increased intraocular pressure that builds up due to blockage or damage of mesh network that drains fluid in the eye. Fluid accumulation can damage the optic nerve over time, if unrelieved, and can cause blindness within a few years, if untreated. Timolol maleate eyedrops are a type of beta-blocker that reduces intraocular pressure by decreasing the amount of fluid secreted into the eye and constricts blood vessels around eyes so that less fluid is filtered into the eye.

In most cases, only about 5 percent of timolol actually reaches the intended site. In other cases, too much medication is absorbed incurring systemic involvement that causes side effects with respiratory and/or cardiac implications, including arrhythmia. To ensure steady medication release over time, the UCLA researchers have integrated timolol maleate with nanodiamonds then affixed them to contact lenses. Drug delivery is triggered by lysozyme—enzyme found in tears—so that timolol is released steadily over a period of time and not released at all when the nanodiamond contact lenses are not in use.

Added benefits include longer durability of the lenses, compared to their regular counterparts on the market, due to the crystalline carbon structure of the nanodiamonds, without affecting optical clarity, lens permeability to oxygen, and water content, so that wearer comfort is maintained.

Nanodiamond contact lenses are one example of increasing incorporation of nanotechnology into medicine, with tremendous potential for optimal glaucoma management—an important protective step for a disease with no current cure.

Silk-Encased Fluorescent Nanodiamonds May Hold Key to Precise Medication Delivery

Scientists from Australia and the United States have discovered a new method to safely view the internal workings of a cell and potentially target a region in the body for precise medication delivery by using silk-encased fluorescent nanodiamonds.

Diamonds are solid substances that are comprised of geometrically organized carbons—the basic atoms of life—and thus stable and harmless. The tiny diamonds can be inserted into living cells and, based on the “flaw” in the gem, absorb light and then emit that light in different wavelengths depending on the material in the nanodiamond—a process called fluorescence.

Silk was incorporated as a coating because the edges around the gem are rough and can get snared in the cell membrane. Lipids, organic molecules found in fats and the basis of cell membrane structure, were originally used to counteract the rough edges, but silk was the better choice due to its transparent, flexible, harmless, and biodegradable nature.

When tested on living tissue, the team of researchers found the “glow” from the silk-encased fluorescent nanodiamonds were 2-4 times brighter because of the silk material and was found to be nontoxic and non-inflammatory, after it left no damage in its wake in the body even after it remained implanted for two weeks.

Silk-encased fluorescent nanodiamonds can equip physicians and researchers with a new approach to viewing cellular activity as it reacts to a new drug. They may also carry medications, such as antibiotics, to a targeted region of the body by having the silk-diamond amalgam directly implanted into the infected area and decrease overall body toxicity levels. The silk, in addition, can be arranged to deteriorate at a predetermined rate for timed-release medication delivery.

Because of their “glowing” nature, silk-encased fluorescent nanodiamonds are lighting the way in the fields of bioimaging, biosensing, and drug delivery mechanisms, and the team hopes to incorporate their findings in medical practice soon.

Gold Nanoparticles for Targeted Medication Delivery and Cancer Treatments

Cells are notoriously protective and do not easily allow particles entry into its domain unless unique transport mechanisms that the cell recognizes are in place. As a result, current medications and treatments do not target specific cell contents and end up destroying the entire cell.

In 2008, researchers discovered gold nanoparticles coated with a one-layer polymer can penetrate cell walls, and since then has recently identified the mechanism of action along with the upper size limit of the particle to effectively penetrate cell walls.

Through a series of lab experiments and computer simulations, researchers at MIT and the Ecole Polytechnique de Lausanne, Switzerland demonstrated the critical step of gold nanoparticles infiltrating the cell wall is to fuse with the phospholipid bilayer of the cell membrane, which is largely the responsibility of the coating on the particle. The coating is a mixture of hydrophobic (“water-fearing”) and hydrophilic (“water-loving”) compounds. Depending on the chemical nature of the compounds used, the upper size limit of the coating was also determined.

A bonus to the team’s discovery was that the method of delivery of gold nanoparticles also sealed the opening after its entry, preventing leaks behind the particle as well as inhibiting damage to the cell as the particle proceeded to the cell’s interior.

The team is hoping to use their discovery as a means of delivering drugs to the cell’s interior by attaching the drugs to the particle’s lipid-mixture coating once they find a way for the coating to be selective on what types of cells they attach to for targeted medication delivery.

The choice to use gold as the coating’s delivery instrument was simply convenient as a research model. However, the team has postulated on a potential health benefit of the precious metal. Gold particles are very good at absorbing x-rays. If the coating can be used to penetrate cancer cells, then the particle can be heated up by an x-ray beam and destroy the malignant cells from within.