Research and Development

Products in Clinical Trials and under development

The pipeline at Lippomix actively seeks new opportunities for research and development. To that end, we are currently involved in cutting-edge research and clinical trials as follows:

Diclofenac

Phase 1 and Phase 2 have been successfully completed in the trial for this advanced pharmaceutical developed for the treatment of inflammation and joint pain. Lippomix is now moving forward into Phase 3.

Curcumin

Believed to be the substance in the spice Tumeric that can reduce swelling and eases symptoms of osteoarthritis and rheumatoid arthritis. Curcumin is virtually insoluble, with almost none being able to be absorbed through traditional nutraceutical delivery systems. This has made Curcumin a "natural" to adapt to liposomal technology. In fact, Lippomix® Patented Technology has achieved 350X the absorption rates of traditional Curcumin.

Glutathione

Known to aid in the treatment of cataracts, glaucoma, asthma, cancer, heart disease, hepatitis, liver disease, alcoholism, memory loss, osteoarthritis, Parkinson’s disease, and more, Glutathione works to maintain the body’s immune system by detoxification. One of the most powerful antioxidants that the body produces, Glutathione is naturally present in the body.

Supplements have a poor absorption rate when taken in traditional forms (insert a journal article here?): therefore, the patient greatly benefits from liposomal technology. Doctors are currently working in conjunction with Lippomix™ specialists on clinical trials of Glutathione.

ASTRAXANTHIN

Research shows that, due to astaxanthin's potent antioxidant activity, it may be beneficial in cardiovascular, immune, inflammatory and neurodegenerative diseases. Some research supports the assumption that it may protect body tissues from oxidative and ultraviolet damage. In addition to the compound’s powerful anti-inflammatory and anti-oxidative capabilities, evidence indicates that astaxanthin has the potential to modulate aging. Oxidative stress is believed to be a principal mechanism of aging so the enhancement of anti-oxidative protection and the inhibition of free radical production are biological pathways that may protect against oxidative damage, mitigating risk for age-associated disease and, perhaps, diminishing the rate of aging. The mechanism by which astaxanthin may be able to modulate aging is activation of the insulin signaling pathway, as well as upregulation of the FOXO3 gene. A 2011 review highlights promising aging-related outcomes in astaxanthin-related clinical trials for model organisms, and in humans.

R-Lipoic Acid

α-Lipoic acid , is a naturally occurring compound that is present in small amounts in the human body. Lipoic Acid synthesysed endogenously bound to proteins and functions as a cofactor for several enzymesSupplementation with high doses of Lipoic acid increases cellular levels of free Lipoic Acid.Although LA is a potent antioxidant, supplementation may improve health by stimulating glutathione synthesis, enhancing insulin signaling, and modulating the activity of other cell-signaling moleculesOverall, the available research indicates that treatment with 600 mg/day of intravenous Lipoic Acid for three weeks significantly reduces the symptoms of diabetic peripheral neuropathy. Lippomix is developing an oral liposome encapsulated, R-Lipoic Acid formulation which will have greatly increased stability and absorption efficacy as compared to conventional products.

Liposomal CoQ10

Coenzyme Q10 (CoQ10) is an antioxidant that is made in the human body. CoQ10 is needed for basic cell function. CoQ10 levels decrease with age and may be low in people with cancer, certain genetic disorders, diabetes, heart conditions, HIV/AIDS, muscular dystrophies, and Parkinson's disease. Some prescription drugs may also lower CoQ10 levels. Lippomix has developed a novel Liposomal og CoQ10 with increased bioavailability and absorption rates.

Tetracaine

Samples for this liposome-encapsulated tetracaine anesthetic (LETA) have been shipped to doctors and other prescribing healthcare professionals. By applying our liposomal technology, Tetracaine has been found to provide a topical anesthesia that goes deeper and has a longer duration that similar products.

Tetracaine belongs to the family of local, aminoester-type anesthetics that includes benzocaine, lidocaine, and prilocaine. This group of drugs is known to reversibly bind to the hydrophobic drug receptor located on the α subunit of many voltage-gated sodium channels. During periods of high frequency channel activity or prolonged membrane depolarization, these ester-type anesthetics bind to the receptor and inhibit sodium current, ultimately inhibiting the propagation of the action potential through the nerve membrane.

Development of Ophthalmic Diclofenac Formulation

The goal of this study was to develop a stable, preservative containing liposome-encapsulated diclofenac formulation for topical ophthalmic application. Small-scale development focused on production of a formulation that was non-irritating to the eye (isotonic, with a pH of 7.2-7.4 and containing little or no organic solvent), resistant to bacterial growth (contained one FDA-approved ophthalmic preservative), stable (resistant to settling of liposomes), and clear. In addition to these criteria, it was also important to determine whether such a formulation could be scaled up for manufacture. Multiple small-scale formulations were created using methods of physical homogenization (sonication, homogenization, heating, freeze/thaw), while a large-scale preparation was created using a proprietary mixing technology (OPTIMIXTM, patent pending). One of the small-scale formulations, (0.1% w/v diclofenac), was tested in rabbits for ocular absorption against a commercially available topical ophthalmic diclofenac formulation (Voltaren ophthalmic (0.1% diclofenac)®). The liposome-encapsulated formulation was found to boost ocular diclofenac concentration 2 fold over Voltaren in the iris-ciliary body, 2.3 fold in the bulbar conjunctiva, 2.5 fold in the aqueous humor, and 3.2 fold in the cornea. No significant drug uptake was seen in the retina, choroid, or vitreous humor, and the liposome-encapsulated formulation did not change the half-life of diclofenac in various ophthalmic tissues. In summary, it appears that liposome-encapsulation of diclofenac increases the ocular absorption of drug over topical application of drug solution alone. Furthermore, using a proprietary manufacturing technology, it appears to be both feasible and economical to produce large-scale batches of liposome-encapsulated diclofenac formulation for ophthalmic use.

Conclusions

This work adds to the growing body of information supporting the use of liposomal suspensions as unique and powerful vehicles for ophthalmic drug delivery. It clearly demonstrates an improvement over an aqueous formulation, with respect to the amount of drug absorbed into several ocular tissues. Although liposome-encapsulated diclofenac formulation increased the total amount of drug delivered, it did not increase the Tmax beyond that seen with Voltaren Ophthalmic®. Future formulation strategies need to include agents that improve the retention of the liposome at the ocular surface. Such agents could include cationic lipids, lectins, or viscosity enhancing agents, and are currently being investigated.

Octylglycerol Microbicide Product

Octylglycerol is a low molecular weight compound that has been shown to have in vitro activity against STD’s including HIV without negatively effecting Lactobacillus crispatus. In order to successfully deliver the active agent octylglycerol, it must be formulated into a stable, safe, and effective dosage form. A liposomal cream formulation was chosen to prolong the residence time of the octylglycerol inside the vagina, and to provide means of targeted delivery to the infectious agents. Lipid to monoglyceride ratio was optimized to maximize in-vitro efficacy while sparing innate micro flora. This formulation was assessed for anti-HIV , HSV, and N. gonorrhoeae activity in vitro. In all cases the active formulation had effectiveness whereas the placebo exhibited no activity. Physical stability of the formulation was assessed by monitoring pH, viscosity, particle size, weight, odor, and appearance. Acceptable physical and chemical stability of the formulation was found for all evaluations made. Studies were conducted to identify the potential for hydrolysis of lipid in this formulation. No hydrolytic degradation products were found when the formulation was evaluated at a number of pH values. These studies showed the chemical and physical stability of the liposomal formulation, as well as the confirmation of its maintained efficacy against HIV, HSV-1, HSV-2, and N. gonorrhoeae.

LIPOSOMAL L-CARNITINE

The goal of this proposal is to develop a new topical formulation for the treatment of intermittent claudication. Intermittent claudication is the primary symptom of peripheral arterial disease, and it affects over 4 million individuals in the United States. Given orally, L-carnitine has shown great promise in clinical trials, however, its bloavailability is poor. Current treatments involve high doses over a prolonged period of time. A more efficient and faster treatment could be provided when the drug is applied topically, thus allowing direct transport into the underlying muscle tissue. To enhance transdermal delivery, L-carnitine will be formulated in a liposomal delivery system, which has already been proven to be successful for the topical delivery of other drugs. First, the carbon chain length of alkyl-L-carnitine will be optimized with respect to encapsulation efficiency and physico-chemical stability of the formulation. Second, the formulation will be optimized with respect to L-carnitine transport through skin in vitro. Finally, in vivo proof of concept will be obtained of L-carnitine delivery into muscle tissue. The best formulation will be identified and developed for further clinical testing. PROPOSED COMMERCIAL APPLICATION: Currently, there is no topical drug treatment for intermittent claudication (IC). Last year a new oral drug (Pletal) was launched. This was the first drug for the treatment of intermittent claudication to reach the market in 15 years. Despite its poor bioavailability and questionable efficacy, this drug grossed 90 million US dollars. This is a striking example of the clinical need for such a drug. A topical formulation should provide a fast and efficient relief from this debilitating disease.

Tacrolimus Topical Immunosuppressive

Psoriasis affects over 7 million people (3 % of the population) in the United States with an estimated 150,000 to 260,000 new cases diagnosed each year. Prograf® (Fujisawa) is currently the lead topical product on the market for the treatment of this disease.

Lippomix’s Product (Advantages over Current Therapies)

Protopic® is a petrolatum based ointment containing the active ingredient tacrolimus. Lippomix has reformulated this product into a liposomal cream which is pharmaceutically more elegant than the current Protopic®.

Ophthalmics

Eye drops are an inefficient means of ophthalmic drug delivery. Approximately 90% of the applied dose is cleared from the ocular surface immediately through blinking, nasolacrimal drainage, and tear production. Consequently, numerous drug delivery vehicles are under investigation in an effort to increase the retention and absorption of ophthalmic drugs.

Lippomix’s Product:

Liposomes are uniquely suited for ophthalmic drug delivery due to their biocompatible and biodegradable nature. Moreover, liposomes have the intrinsic ability to bind to epithelial tissues, i.e. allowing them to retain the drug longer at the surface of the eye. It has been shown that liposome mediated drug delivery to the eye is considerably more effective (2-3 fold) than application of drugs in solution (Figure 4).

In spite of their apparent effectiveness, there are no commercially available liposomal formulations for ophthalmic use. Difficulty in manufacturing liposomes is the main reason for this. Methods most commonly used to produce liposomes require the use of chloroform or other organic solvents. Carry over of these organic compounds into the final product may result in ocular irritation or damage and is pharmaceutically unacceptable. In addition, ophthalmic formulations require buffering and the presence of a preservative, which often cause disruption of liposomal structures. Finally, it is essential to control the size of liposomes. Smaller liposomes will render more stable, less turbid suspensions. These difficulties have hampered the development of liposomal formulations into commercial products for ophthalmic use.

Lippomix has solved these problems by using its unique and proprietary liposome manufacturing technology.

Magnesium Sulfate Nasal Spray

Prevalence of allergic rhinitis in the U.S. population is enormous. For oral antihistamines alone, there were 51 million prescriptions in 1999. Due to its widespread nature, allergic rhinitis is a particularly troublesome hypersensitivity reaction. Hay fever occurs in response to allergens such plant pollens, fungi, animal dander, and dust mites and is characterized by mucosal edema, itching, redness, and mucous secretion from nasal and lacrimal glands. There are many products on the market to suppress the symptoms of allergic reactions efficiently. However, many of which contain steroids or corticosteroids which can cause significant adverse effect when used chronically. Therefore, there remains a need for safer products that offer effective relief of such symptoms.

GENE PRODUCTS UNDER DEVELOPMENT AT LIPPOMIX

Lippomic Inc. has unique technology to deliver gene therapy products locally instead of systemically. Lippomix’s plan will center on the development of these proprietary technologies to provide superior gene delivery vehicles to specialized tissues. Localised application will minimize systemic delivery and distribution throughout the body. This technology will maximize gene delivery to the affected areas and decrease side effects. The ease of a topical treatment and administration will allow patients to forgo invasive procedures which may require hospitalization.

Lippomix will focus on the following three areas for gene delivery:

  • Wound healing
  • Cervical cancers
  • Diseases of the eye