Creating an Effective Nab Paclitaxel Drug Delivery System

According to the American Cancer Society, over 1.8 million new cancer cases are diagnosed each year in the United States alone. Globally new cancer cases are estimated to be around 19.3 million per year.¹ Although the World Health Organization reports cancer as the second leading cause of death globally, strides in research and development in the field of oncology are being made every day.²

In the war on cancer, chemotherapy plays a vital role in delivering essential drugs to the body to help destroy, shrink and/or control cancer cells. Chemotherapy continues to be one of the most problematic and promising cancer treatments today. As opposed to radiation or surgery which targets a specific cancerous region, chemotherapy delivers drugs throughout the body. However, due to their high toxicity, chemotherapeutic agents can cause severe side effects. Delivering chemotherapeutics to targeted tumor sites presents numerous challenges due to drug payloads’ high toxicity, low aqueous solubility and poor bioavailability nature but nanotechnology can help achieve such a targeted delivery.

The Nanoparticle Albumin Bound (nab) Paclitaxel Advantage

One of the more beneficial chemotherapeutic delivery platforms is nanoparticle albumin bound (nab) paclitaxel due to its high efficiency and improved tolerability. Paclitaxel is a taxane, antimicrotubule agent used in the treatment of numerous cancers and although highly toxic, it is a very effective mitotic inhibitor.³ Albumin is a water-soluble protein derived from plasma which due to its natural makeup has the benefit of being both biocompatible and biodegradable. It, therefore, has the added benefit of possessing lower toxicity and immunogenicity than its solvent counterparts, Cremophor EL and ethanol. The natural properties of albumin makes it a favorable vehicle for delivering therapeutic agents (such as Paclitaxel) to targeted tumor sites. Previous solvent delivery carriers exposed patients to toxicities causing severe side effects from both the solvent and the drug itself. Human serum albumin (HSA) delivers cancer chemotherapeutic to the tumor site through several different pathways where the drug (paclitaxel) blocks the growth of the cancer, prevents the cancer cells from dividing and finally kills the cancer cells.

Abraxane^® was the first FDA approved drug developed using nab paclitaxel technology and it is a powerful chemotherapeutic drug designed to stop cancer cells from repairing and multiplying. Abraxane^® is used in the treatment of advanced, spreading pancreatic cancers, metastatic breasts cancer and non-small cell lung cancers and has been shown to prolong the life of its recipients.

The Challenges

Albumin bound (nab) paclitaxel chemotherapeutic drugs, such as Abraxane^®, are injected directly into the vein, commonly known as intravenously. This direct access into the blood stream has the benefit of immediate response, however, it also presents sterilization challenges in the development and manufacturing process. Therefore, albumin bound paclitaxel chemotherapy drugs must take into effect sterile filtration during processing.

Another major challenge is how to combine two immiscible substances, albumin (an aqueous protein) with paclitaxel (a solvent-based agent) - so they mix together, stay together and provide consistent distribution from application to application. In the case of Abraxane^®, not only small particles, e.g., mean particle size around 130 nm, are needed but a tight particle size distribution is required.

How to Produce Nab-nanoparticles 

The best and proven way to create nab-nanoparticles is through the process of emulsification.

• In the first step, the active ingredient (paclitaxel) is dissolved in an organic solvent to form an oil phase.
• Next, paclitaxel solution (oil phase), is mixed, with an aqueous phase (an albumin solution) and processed usually with high shear, to create a nanoemulsion.
• Lastly the nanoemulsion will undergo solvent removal, sterilization and lyophilization steps to create the end powder form product.

How Microfluidizer^® Technology Fits In

Microfluidizer^® technology is a proven technology in nanoemulsion applications, which is a critical step in creating the nab paclitaxel nanoparticles which require precise particle size control. Drug delivery nanoemulsions must be sterilized and sterile filtration is a cost efficient and gentle method. Through Microfluidizer’s^® technology, very narrow particle size nanoemulsions are created and can pass through sterilizing filters without losing product or clogging the equipment which would hinder production. Microfluidizer^® processors not only produce stable emulsions but also facilitate efficient sterile filtration which comply with cGMP regulations.   

Microfluidizer^® processors deliver uniform high shear during processing. This controlled precision allows for repeatable results regardless of volume size. In chemotherapeutic production, repeatable tight particle size distribution is essential in creating a consistent product. With Microfluidizer^® technology, narrow particle size is duplicated batch-to-batch and is scalable from lab to pilot-scale to manufacturing. Microfluidics’ revolutionary Interaction Chamber™ allows scale up capabilities through a microchannel system to deliver optimal production rates and fewer defects. By producing narrow particle size distribution, greater stability and longer shelf life can be achieved. 

Microfluidizer^® technology has proven results in nanoemulsion application in the following fields:

• Pharmaceutical/Vaccine
• Cosmetic/Personal care
• Food/Nutraceutical
• Chemical

Our Microfluidics team has years of expertise helping businesses achieve their goals. Our superior knowledge is here to help you obtain superior results.

References

¹https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2020.html

²https://www.who.int/news-room/fact-sheets/detail/cancer

³https://www.verywellhealth.com/taxol-paclitaxel-chemotherapy-430562