Medlab Delivery Platform

WHAT IS NANOTECHNOLOGY

Nanotechnology describes the science, engineering and technology that is conducted at the nanoscale that deals with particle dimensions of less than 100 nanometres. This is functional systems at the molecular scale.


A COMPREHENSIVE DEFINITION IS

The design, characterization, production, and application of structures, devices, and systems by controlled manipulation of size and shape at the nanometer scale (atomic, molecular, and macromolecular scale) that produces structures, devices, and systems with at least one novel/superior characteristic or property.


WHY ITS USE IN MEDICINE IS IMPORTANT

The application of nanotechnology in medicine offers exciting possibilities from its application to drug delivery...to therapy techniques...to diagnostic techniques...to anti–microbial techniques...to cell repair.

Utilising small particle size technology such as nanoparticles can further enhance the medical delivery and hence efficacy of pharmaceutical, nutraceutical and herbal medicines such as cannabis.



Source: Adapted and modified from CA CANCER J CLIN 2013;63:395–418

MEDLAB'S ROLE and USE OF NANOTECHNOLOGY

Research in the nanotechnology space is to further characterise important submicron particle features that may value add to Medlab's patented technology by enhancing the science and hence efficacy of medicinal compounds such as Vitamin D3, Ascorbate, Vitamin B12,and whole plant extract cannabis.

Beyond the Cannabis application, Medlab sees a real benefit in repurposing many generic pharmaceuticals with a lower dosage format and reduction in reported side effects. Medlab's pharmaceutical agenda has brought-about development in NanoCelle'ed Statins, Insulin, Steriods, ACEi's, Antibiotics, and immunosuppressive Agents to name a few. See Currently in Development, below.

Notwithstanding, whilst Medlab favours the buccal route, application for NanoCelle'ed API delivery is underway for nasal and topical as well.


Medlab's NanocelleTM Key-Points


  • Buccal / Nasal administration is preferred route for drug development
  • < 60% marketed drugs are via oral gastrointestinal administration
  • Bioavailability of orally administered drugs strongly influenced by their solubility and permeability across the gastrointestinal (GIT) mucosal epithelium
  • Most orally administered drugs display low systemic availability and diminished efficacy - due to drug formulation, GIT physiology & first pass metabolism
  • Particle range is 3.8 - 89.31nm validated by US reference lab

  • While submicron particle suspensions have complex particle size distributions in that the particle size distribution is broad consisting of several distinct particle populations of varying sizes where most have greater than 100 nanometres particle sizes (e.g., emulsions, liposomes), Medlab's nanocelle patented technology was developed with research on submicron particles spanning more than two decades. Demonstrating critical sub micron particle size characteristics well below 100 nanometres.


    THE NEED FOR 3RD PARTY VALIDATION

    Who we use and why


    Particle Technology Labs, LTD

    PTL is a premier particle technology research and advisory company. We are a trusted advisor to the world's leading pharmaceutical, industrial, public sector and scientific organizations. We work with, and provide advice to, major organizations across the private, public, and scientific research sectors. PTL is free from all commercial bias.

    Particle Technology Labs currently has the capability to provide this service in-house using our NanoSight LM10-HSBT14, which is the first cGMP-certified instrument of its kind in the United States. The NanoSight LM10-HSBT14 utilizes Nanoparticle Tracking Analysis (NTA) technology, which is one of the first commercially available technologies allowing high-resolution particle size distribution on a number-weighted basis and concentration analyses of submicron particles.

    NTA technology employs the following steps:

    • A highly focused laser passes through a liquid dispersion in a specially designed cell.
    • As the nanoparticles in the dispersion interact with the laser, they are observed as points of light moving under Brownian motion through a microscope.
    • The rate at which the particles move is a function of their diffusional rate, which is in turn a function of their size as given by the Stokes-Einstein equation.
    • By tracking the motion of each particle over a specified amount of time, the diffusional rate can be measured and the particle size calculated.
    • Since the cell is a known volume and the particles present are individually counted, an accurate particle concentration can be calculated simultaneously.

    ASTM E2834-12 describes this innovative technique and provides guidance for industry use.

    Another option that PTL has for the analysis of submicron particles is through Dynamic Light Scattering (DLS).

    DLS is a commonly-used term to describe a technique which measures the particle size and estimated distribution of submicron particulate systems on an intensity-weighted basis. In addition, the terms Photon Correlation Spectroscopy (PCS) and Quasi-Elastic Light Scattering (QELS) have also been used historically to refer to the same analytical principle. By any name, the technique is widely recognized throughout the pharmaceutical and industrial world reflected in the existence of several standards describing the technique (i.e. ISO 22412, ISO 13321, and ASTM E2490-09).

    DLS requires particles approximately less than a micron in size to be homogenously suspended in a fluid (aqueous or organic). A few examples of suitable systems could include:

    • aggregated proteins
    • pigment components
    • micelles
    • emulsion droplets suspended in a continuous phase

    DLS technlogy employs the following steps:

    • The nano-dispersed system is placed into the optical path of a LASER.
    • The LASER is then scattered upon interacting with the particles in the suspension, which are moving by Brownian motion.
    • The scattered light is captured by a detector over the course of the analysis to determine the rate of diffusion (i.e. how fast the particles move within a system due to Brownian motion).
    • The average hydrodynamic particle size (referred to as the Z-Average) is calculated on an intensity-weighted basis using the Stokes-Einstein equation.

    In simple terms, small particles move/diffuse more rapidly than larger particles.

    While other reporting formats are available, the most widely accepted and recommended way to report results from DLS is on an intensity basis using the Z-Average along with the Polydispersity Index (PDI). The PDI is an indicator of the “broadness” of the particle size distribution. DLS technology also allows for the determination of the critical micelle concentration (CMC) for various surfactants. In addition, a DLS instrument at PTL is capable of determining zeta potential in an aqueous suspension as well as isoelectric point determination (IEP).


    Sample report for Medlab's Perindopril Erbumine here


    Sample report for Medlab's Atrovastatin here


    NANOCELLE

    Please see below an example of Medlab's nanotechnology.


    Administration and route of absorption


  • 40-50 cell layers thick
  • More permeable to water-soluble drugs than keratinized epithelia i.e. hard palate
  • Blood flow faster / richer compared to sublingual, gingival and palatal regions
  • Passive diffusion of NanocelleTM drug molecules facilitated and enhanced

  • GIT Barrier to Drug Absorption / Bioavailability


    B12 EXAMPLE

    Comparative blood work

    HREC Number: 003/032014

    N=40



    STATIN EXAMPLE

    14% of tablet is active, side effects - opportunity to improve



    Atorvastatin in water (1.7 mg/mL) and Nanocelled Atorvastatin (1.7 mg/mL) Rosuvastatin in water ( 5 mg/mL) and Nanocelled Rosuvastatin ( 10mg /mL)

    CURRENTLY IN DEVELOPMENT

    Table of particle sized API's


    Particle Particle Size (nm) Concentration Dosage
    Ampicillin Sodium Salt (2162016AMP)- antibiotics 12.85 2 mg/mL 0.6 mg/0.3mL
    Atorvastatin (1022015ATO) 11.41 10 mg/mL 3 mg/0.3mL
    Atorvastatin (1232015ATO) 89.31 0.1 mg/mL 0.03 mg/0.3mL
    Atorvastatin (03212017ATO) 14.4 8.3 mg/mL 2.49 mg/0.3mL
    Atorvastatin (3152017ATO) 19.37 13.3 mg/mL 3.99 mg/0.3mL
    Atorvastatin-25 (12142015ATO25) 14.62 1.67 mg/mL 0.5 mg/0.3mL
    Atorvastatin-30 (12142015ATO30) 14.37 1.67 mg/mL 0.5 mg/0.3mL
    Atorvastatin (2162016ATO) 12.71 10 mg/mL 3 mg/0.3mL
    Beta-Estradiol (2162016EST)-hormones 16.43 1 mg/mL 0.3 mg/0.3mL
    Fexofenadine (TelfastTM) 10.6 4 mg/mL 1.2 mg/0.3mL
    Dexamethasone (2162016DEX)-hormones 13.17 2.6 mg/mL 0.78 mg/0.3mL
    Insulin (1022015INS) 3.843 15 IU/mL 4.5 mg/0.3mL
    Perindopril Erbumine (2162016PER)-ACEi 12.7 7 mg/mL 2.1 mg/0.3mL
    Progestogen (2162016PEO)-hormones 15.48 2 mg/mL 0.6 mg/0.3mL
    Rosuvastatin (1022015ROS)-statin 12.19 2 mg/mL 0.6 mg/0.3mL
    Rosuvastatin (1022015ROS)-statin 12.19 2 mg/mL 0.6 mg/0.3mL
    Sertraline Hydrochloride (2162016SER)-SSRI 15.21 0.5 mg/mL 0.15 mg/0.3mL
    Testosterone Propionate (123015TES)-hormones 14.31 15 mg/mL 4.5 mg/0.3mL
    CoQ10 (2182916CoQ10) 32.3 100 mg/mL 30 mg/0.3mL
    CoQ10 (2182916CoQ10) 32.3 100 mg/mL 30 mg/0.3mL
    D3 194 3333 IU/ mL 1000 IU/0.3 mL
    D3 & K2 (2182016D3K2) 28 3333 IU+150mcg/0.3 mL 1000 IU+45 mcg/0.3 mL
    Melatonin (2182016MEL) 23 8.3 mg/mL 2.5mg/0.3mL
    Cyanocobalamin B12 24.8 3333 IU/ mL 1000 IU/0.3 mL
    Methylcobalamin B12 (2182016B12) 18.9 3333 IU/ mL 1000 IU/0.3 mL
    Vitamin A Tropical with Zinc To be tested 20000 IU Vitamin A with 1333 mcg Zn/mL 6000 IU Vitamin A with 400 mcg Zn/0.3mL
    Hemp Seed Oil Tropical To be tested 33.3 mg/mL 10mg/0.3mL
    NanaBidialTM (CBD) To be tested 8.3 mg/mL 2.5mg/0.3mL
    NanaBisTM (CBD+THC) To be tested 8.3 mg/mL 2.5mg/0.3mL