TRIOZAN™ Nanomedicine Delivery Platform

The platform exploits TRIOZAN™ (N,N,N-Trimethyl Chitosan) which is a novel, best-of-its-kind, protected biopolymer that could be used in nanoparticle/microparticle or excipient forms conferring multiple therapeutic application advantages involving various possibilities of therapeutic enhancement through reformulation and repurposing of existing drug molecules (including biologics) from the initial drug introduction in the body until it is delivered inside the targeted cell. Indeed, it provides several therapeutic enhancement capability options such as the change of routes of administration, blood-brain barrier (BBB) crossing property, drug bioavailability enhancement, drug reduction in healthy tissues, and intracellular drug delivery improvement.


More specifically, TRIOZAN™ is a safe, biodegradable and biocompatible hydrophilic and highly quaternized biopolymer with advantageous physicochemical properties that enables an efficient encapsulation and protection of drug molecules against degradation while simultaneously maintaining therapeutic integrity. It is a potential multi-targeted combinations nanoparticle carrier containing a drug payload that can be engineered in a controlled manner to provide advanced targeting capabilities. It has the ability to accumulate in the targeted tissues with minimal loss while circulating in the blood. Finally, it enables the controlled release of the therapeutic active in a more specific manner inside tissues and cells.

ROUTES OF ADMINISTRATION

TRIOZAN™ Nanomedicine Delivery Platform presents itself as a pharmaceutical polymeric nanocarriers allowing the efficient delivery of a wide range of drug molecules (peptides/proteins, DNA/RNA & gene based therapies, small molecules) across multiple barriers, including but not limited to:

  • Blood-Brain Barrier (BBB)
  • Buccal
  • Bronchial
  • Cornea and conjunctiva
  • Dermal
  • Female reproductive tract
  • Gastrointestinal tract
  • Nasal
Multi-Combination


BLOOD-BRAIN BARRIER CROSSING PROPERTY

TRIOZAN™ Nanocarriers could be used to cross the BBB through the Adsorptive-Mediated Transcytosis (AMT) mechanism.


AMT is triggered by an electrostatic interaction between the positively charged moiety of the carriers and a negatively charged plasma membrane surface region on the brain capillary endothelium.

The nanocarriers accumulate in the brain tissue with minimal loss while in the blood circulation, and provide a controlled release of the therapeutic molecule inside the brain tissue.


DRUG BIOAVAILABILITY
ENHANCEMENT


DRUG REDUCTION IN
HEALTHY TISSUES

TRIOZAN™ Nanocarriers readily penetrates the Luminal Mucus Layer (LML) and enters the underlying Adherent Mucus Layer (AML) due to high electrostatic interaction with the epithelia layer. It allows to counteract against clearance mechanisms and to prolong residence time of nanocarriers at the mucosal surface. TRIOZAN™ Nanocarriers will provide an essential protection of drug molecules (small molecules and biologics) from enzymatic degradation while enhancing their absorption across mucosal membranes through mucoadhesiveness and the transient and reversible opening of epithelial tight junctions by JNK-dependent pathway mechanism to fully reach the systemic circulation without altering their biological activity. TRIOZAN™ Nanocarriers could also be engineered with the goal to optimize the nanocarriers residence time in the GI Tract making them a potential targeting tool for various GI Tract related diseases.

TRIOZAN™ Nanocarriers could be functionalized with specific ligands in order to provide additional precision, efficacy and less adverse effects. With respect to cancer indications, TRIOZAN™ Nanocarriers are accumulated into the tumor via the enhanced permeability and retention (EPR) effect allowing for the extracellular controlled release delivery of the drug payload. Indeed, the nanocarriers travel through normal blood vessels with a prolonged circulation time and cannot pass through the tight junctions between endothelial cells (only epithelial cells), thereby minimizing toxicity in normal tissues. At the same time, they accumulate in the tumor sites where endothelial cells are leaky and achieve controlled and sustained drug release with enhanced intracellular accumulation as well, thereby maximizing the efficacy drug profile. Thus, TRIOZAN™ Nanocarriers could favor tumor regression with minimal signs of systemic toxicity.


INTRACELLULAR DRUG DELIVERY IMPROVEMENT

On the intracellular level, the uptake of TRIOZAN™ Nanocarriers is achieved mainly via the Caveolae-Mediated Endocytosis (CvME) and possibly the CD44-Mediated Endocytosis. Indeed, CD44 receptors are overexpressed in several solid tumor cells and TRIOZAN Nanocarriers may have the capability to target overexpressed CD44 active receptors on cancer cells and cancer stem cells in the tumor microenvironment.



The internalized nanocarriers can be stored in non-acidic, non-degrading cellular compartments, where the nanocarriers act as reservoirs for slow, long-lasting release of their payload due to the interaction with the anionic proteins coating the inner surface of the caveolae-mediated vesicle (endosome).


The electrostatic interactions allow for the efficient disruption of vesicle membranes leading to drug escape in the cytoplasm and/or in the Golgi/ER system. TRIOZAN™ Nanocarriers can interact with the proteins in the membrane of the early endosomes, late endosomes, phagosomes (e.g. phagocytosis), lysosomes and other intracellular transport vesicles.

Drug Internalization
CD44 on Normal and Cancer Stem Cells