Nanovex Biotechnologies applications

Antigens can be carried by liposomes, either lipids, proteins, DNA or RNA. They can also be combined with bacteria or virus components to form archaeosomes or virosomes, respectively. These vaccines have been proved to be effective in inducing immune responses and providing a sustained exposure to the antigen. More than 30 clinical trials are currently using liposomes for vaccine delivery including HIV and several types of cancer.

The use of genetic material as therapeutic compounds to adjust dysfunctional cell behaviors is a revolutionary approach that has gained more attention in recent years in the medical field. Up or downregulation of genetic expression leads to an increased or decreased production of proteins respectively. The main challenge that gene therapy faces with naked genetic material is the low transfection rates and thus, therapeutic efficacy. Their physical properties as big sizes and polarity, difficult the permeation thought cell and nucleus membranes as well as are susceptible to enzymatic degradation.

The development of highly cytotoxic drugs is needed for the success of the treatment in tumor cells. Paradoxically, the high toxicity limits its efficacy and application in vivo, causing damage to non-target organs and severe secondary effects. The use of directed liposomes has allowed the advance of many cancer drugs to preclinical and clinical trials, reducing side effects, and increasing their therapeutic index at the same time. More than 15 cancer liposomed drugs are currently clinically available.

The defense mechanisms observed in the eye (epithelium, tear flow and blinking reflex) hamper the drug penetration into deeper layers of the eye. The use of modified liposomes with mucoadhesive polymers and a specific lipid formula helped in overcoming these surface obstacles and reaching target areas as the conjunctival sac.

The trespassing of the blood brain barrier is a challenge for the treatment of central nervous diseases such as Alzheimer, Parkinson, stroke, or cancer (glioma). The endothelium shows tight junctions and specialized transporters which limits the bioavailability of drugs in the central nervous system.

The increase or decrease of a natural immune response to obtain a therapeutic result is the basis of immunotherapy. It holds great promise for the treatment of autoimmune diseases, cancer, and the prevention of transplant rejection.

Tissue regeneration is aimed at the reconstruction of a tissue or organ that requires that cells coordinate timely and spatially to proliferate and differentiate. This comprises complex cell signaling to regulate cellular activity. The delivery of growth and differentiation factors face a rapid in vivo clearance that will benefit greatly from encapsulation in liposomes. Apart from protection, liposomes target the specific cell populations to develop in a scaffold and allow a spatio-temporal controlled delivery. Wound healing is another field in which liposomes have been used with great outlooks, specially for impaired wound healing cases, protecting short life pharmaceuticals, and accelerating neovascularization and epithelialization.

PLGA nanospheres have already been successfully used in vitro and in clinical trials. Results show that drugs encapsulated in PLGA nanoparticles have superior accumulation in the tumor environment, reduced tumor size and enhanced inhibition of cell proliferation. This is thanks to increased cell penetration and reduced toxicity of encapsulated compounds. Because of the higher accumulation in tumoral areas PLGA nanoparticles are also useful for cancer diagnosis and imaging which has a key role in clinical oncology to early detection and accurate prognosis. The greater therapeutic index of encapsulated paclitaxel, cisplatin and mitoxantrone among other chemotherapy drugs over their equivalent clinical counterparts has been proved multiple times.

Detection and characterization of exosomes is necessary to stablish a relationship to disease and therapy. However, the low quantities obtained during isolation together with its cost, does not make it the ideal control for the development of reliable detection techniques. Synthetic exosomes are a very interesting tool to use as a standard in different applications such as the validation of exosome isolation tools or detection systems, among others.

Like other nanocarriers, synthetic exosomes can be used to treat different types of cancer successfully, by encapsulating the desired anti-tumoral drug or RNA and enzymes. Several studies have used engineered exosomes from dendritic or macrophage cells to release chemotherapeutic compounds as doxorubicin, paclitaxel miRNA or siRNA to induce antitumoral activity. Rodent mammary carcinoma, mice lung cancer, glioma and pancreatic cancer are just some targeted diseases in preclinical testing using exosome delivery technology. Examples of peptides and targeting ligands for exosome decoration are integrin specific RGD for mice mammary tumor or GE11 synthetic peptide for EGFR+ breast cancer.

Downregulating the immune response is necessary for the treatment of autoimmune diseases. In this aspect, the APO2L/TRAIL ligand is a key intermediate in immune cascades and is secreted in exosomes in natural conditions. Its alteration has been associated with rheumatoid arthritis. The administration of synthetic exosomes decorated with APO2L/TRAIL has been shown to be effective in reducing the hyperplasia and overall inflammation in this disease.

Exosomes are natural genetic material carriers, including mRNA, miRNA and siRNA. This material cannot be used in its naked form since it is very sensitive to degradation by ribonucleases, and it cannot enter the cells freely. Encapsulation in synthetic exosomes is an advantageous approach: it preserves the RNA and allows a path for cell uptake.

The delivery of therapeutical compounds such as RNA drugs into the brain presents the challenges of RNA preservation and the crossing of the blood brain barrier. Exosomes loaded with the specific siRNA sequences and marked with the neuron specific RVG peptide show specific accumulation in neurons, microglia and oligodendrocytes in the brain, effectively reducing genetic expression. This is a potential approach for brain diseases like Alzheimer, while reducing side effects due to unspecific tissue targeting.

Drug delivery in the retina is normally performed through intravitreal injection but it is only suitable for compounds fitting a list of criteria like long half-lives. Decoration of engineered exosomes derived from retinal cells with hyaluronan binding peptides is a very effective alternative to intravitreal injection. Hyaluronan can be found in high concentrations in the vitreous of the eye, and thus, this strategy enhances the penetration and uptake from retina cells.