DFB Pharmaceuticals
Practical innovations for life

Drug development

NanoPac® & NanoDoce®

 

Taxanes

  • Paclitaxel/Docetaxel
  • The world’s most prescribed chemotherapeutic agents
  • Indicated for breast, ovarian, head/neck, gastric, pancreatic, prostatic, non small-cell lung, and other cancers
  • Have antiproliferative, antiangiogenic, and anti-inflammatory activity
  • On the World Health Organization's Model List of Essential Medicines

Currently available taxane formulations have significant challenges

  • Intravenous administration causes significant systemic side effects due to cytotoxic nature of taxanes
  • Poor aqueous solubility requires formulating with co-solvents which produce their own set of significant side effects
    • Cremophor® for paclitaxel
    • Ethanol/Polysorbate 80 for docetaxel
  • These serious side effects further limit both dosage and frequency of dosing
  • Taxane blood levels fall below therapeutic levels in under 24 hours – yet drug administration must be limited to every 2-3 weeks

Advantages of NanoPac® and NanoDoce®

Features:

  • Formed in a patented, controlled nanoparticle production process using ultrasound and supercritical fluid carbon dioxide causing up to a 400 fold reduction in mean particle size
  • Stable, uncoated “naked” submicron particles with narrow distribution around the mean particle size
  • Unlike conventional micronization via milling, no energy is added to the nanoparticles allowing them to remain free-flowing, stable, suitable for pharmaceutical manufacturing without solvents
  • Exponential increase in surface area enhancing suspendability of hydrophobic drugs in simple liquids

Imagine 400 times smaller.

The model airplane in this picture is approximately a 1:400 scale model of an actual plane. This is the same mean reduction achieved in our conversion of unprocessed crystalline paclitaxel to NanoPac® Nanoparticle Paclitaxel.

Benefits:

  • Significantly increased bioavailability at treatment site due to enormous surface area of the nanoparticle versus unprocessed paclitaxel or docetaxel crystals
  • Local delivery results in greater efficacy than systemically delivered paclitaxel or docetaxel
    • Much higher concentration of drug at the treatment site relative to amount able to reach treatment site via systemic delivery
    • Remains at therapeutic levels 24 hours a day for weeks as nanoparticle steadily dissolves at site of administration
    • In a phase 1 clinical trial, intraperitoneal paclitaxel concentration of IP-delivered NanoPac® Nanoparticle Paclitaxel was 375 to 2000 times greater than IP concentration of systemic paclitaxel alone and remained at therapeutic levels for more than 14 days
    • Preclinical studies show clearance is primarily through lymph system with drug found in lymph nodes
    • Topically applied NanoPac® Nanoparticle Paclitaxel penetrates through the epidermis and dermis
  • Local delivery results in a better safety profile than systemically delivered paclitaxel or docetaxel
    • Side effects of local delivery are insignificant relative to systemic delivery
    • Systemic clearance of locally delivered NanoPac® Nanoparticle Paclitaxel and NanoDoce® Nanoparticle Docetaxel has been demonstrated to be well under level of toxicity
    • In a phase 1 clinical trial, topically applied NanoPac® Nanoparticle Paclitaxel resulted in no dermal irritation, no other local or systemic side effects, and negligible systemic clearance
  • Flexibility to be formulated into multiple local delivery forms:
    • Saline suspension for intraperitoneal (or other compartmental ) instillation or infusion
    • Saline suspension for direct injection into tissue, tumors, or cysts
    • Homogeneous suspension in a proprietary anhydrous siloxane emollient base for topical delivery
    • Powder suitable for nebulized inhalation
  • Strong IP portfolio covered by more than 40 patents or patent applications and growing