What can you say about the safety of Novochizol?
We believe Novochizol is as safe as its starting material, chitosan (GRAS).
Novochizol nanoparticles have been tested extensively in a preclinical setting in human cell lines, mice (intramuscular, intracardial, intestinal injections, brain – dural graft substitutes, ocular applications),
pigs (intra-pulmonary aerosols, intracardial and renal artery injections), dogs (brain – dural graft sustitutes), chicks (ocular applications), rabbits (ocular applications)
No clinical studies have yet been conducted as part of any drug development program.
What can you say about the genotoxicity of Novochizol?
We have completed a full cycle of preclinical studies for a combined preparation with botulinum toxin for injectable use. No genotoxicity was observed. There are minor problems with apyrogenicity, which are solved by special methods that exclude the ingress of pyrogens in raw materials. In acute and chronic toxicity tests, the NOVOCHIZOL- botulinum formulation was less toxic than the original botulinum toxin.
What evidence supports Novochizol adhesion to specific tissues?
- We have microscopic data on the binding on the cornea and the endothelium of the intestine with penetration into the cells.
- We have data from immunohistochemical studies on the penetration of botulinum toxin into muscle cells. The cells that are not directly exposed to the botulinum toxin-Novochizol nanoparticles temain toxin-free. The denervating effect is only observed in muscles wehere the injection was made. No systemic effects can be observed, event at very high doses of toxin, up to 75 LD50 (mice) for 1 rat.
- We have data on injections into the renal artery of highly active pharmaceutical ingredients and we consistently observe that the biological responses are strictly local, confined to the kidneys.
How do you know that Chitosan’s biological activities are preserved in Novochizol?
We always compare the biological activity with the original chitosan. For example, the original chitosan enhances the denervating effect of botulinum toxin, but since we can measure it quantitatively in Volts, we see how much the effect is enhanced with Novochizol,compared to chitosan. We can say the same about the transport function of the Novochizol compared to chitosan. Microscopically, we see a noticeable difference with chitosan. Thus, the biological effect is measured either as a percentage of the increase in denervating ability, or, if chitosan does not show visible activity, then simply as an effect. We see a much more pronounced effect when applied to the cornea or when penetrating into the endothelium of the intestine, or when penetrating into leukocytes. Some effects we evaluated subjectively. Thus, when assessing effects on sunburns, half of the affected back was treated with chitosan, and the other half with Novochizol. Visually, the next day, the redness was substantially decreased in the latter. Subjectively, the pain was significantly reduced or even absent when Novochizol was used.
What evidence supports Novochizol antimicrobial effects?
Novochizol has bacteriostatic properties and is a poor medium for the growth of bacteria. Moulds (mukor) from the environment can hardly grow in Novochizol solutions. We are now conducting tests with bacterial cultures to assess antibacterial poperties. We performed a number of surgical operations to implant products impregnated with Novochizol. The animals appeared healthy throughout the long-term assessments of biocompatibility of implants over periods of up to 6 months. There were noinfections, suppurations or abscesses.
What is the scale of your manufacturing process?
450 grams per batch. It is easy to scale-up the process since there are no large thermal effects, the reactions do not proceed too quickly and there is ample time for adequate mixing.
How much time do you need to produce a Novochizol drug formulation from an existing API?
Between 48 and 72 hours of dedicate time.