Part 1: Polymeric Nanoparticles

Introduction:
Nanotechnology in the Pharmaceutical Industry

Part 1 of 4: Polymeric Nanoparticles

“Nanotechnology” and “nanoparticles” in the pharmaceutical industry are particularly broad terms, used to describe a range of modern approaches to drug delivery. These technologies are designed to overcome the deficiencies with traditional pharmaceuticals such as low aqueous solubility, rapid elimination, systemic toxicity, low cellular uptake, and poor drug stability.

We love nanotechnologies and want you to love them too. In this 4-part series, we will introduce some of the well-established nanoparticle technologies, highlighting their benefits. We’ll conclude each part of the series discussing emerging technologies we think are noteworthy. Today in Part 1, we’ll discuss Polymeric Nanoparticles.

Part 1: Polymeric Nanoparticles

These nanoparticles are comprised of a drug—typically a hydrophobic one— encapsulated, complexed, or absorbed on a macromolecular complex of polymers. The polymers employed can be naturally occurring or derived, as well as man-made. Examples include:

1. Polysaccharides – biocompatibility and in particular biodegradability is the major advantage of this class, with their glycosidic bonds often cleavable by endogenous enzymes. Examples include, cellulose, chitosan, hyaluronic acid, and the cyclodextrin derivative Captisol® (sulfobutyl ether beta-cyclodextrin) used in VEKLURY® (remdesivir).
2. Poly(amino acids) – This group includes smaller (<1000 kDa) polymers up to large proteins. As with polysaccharide, the biggest advantage of these polymers is biocompatibility and biodegradation. Paclitaxel bound with albumin protein (ABRAXANE®) is the classic example in this class.
3. Poly(esters) – versatility is the biggest advantage of this class of polymers. Since these are man-made, the composition can be easily adjusted to meet solve a particular drug delivery challenge. For example, by changing the ratio of 2 monomers in poly(lactic acid-co-glycolic acid) (PLGA) polymers, the crystallinity and drug-loading properties can be modified. The triamcinolone acetate extended release injectable ZIRLETTA® is 75:25 PLGA in microsphere form.
4. Poly(ethylene) glycols (PEG)– these polymers are the most ubiquitous man-made polymers in the pharmaceutical industry. Part 2 of our series will cover PEGlyated drugs, here is focusing on amphophilic block polymers with PEG serving as the hydrophilic block. A seemingly endless number of PEG co-polymers have been used in drug delivery: PEG-polycaprolactone (PCL), PEG- poly(lactic acid-co-glycolic acid) (PLGA) polymers, PEG-poly(propylene oxide) (PPO), and PEG-poly(amino acids) are commonly utilized in drug delivery. Approved in South Korea, GENEXOL-PM® is a polymeric micelle formulation with the oncology drug paclitaxel and PEG-block-poly(D,L-lactide) (PEG-PDLLA) which allows for higher dosing with less hypersensitivity compared to the equivalent Cremophor formulation (TAXOL®). Yet another class are the PEG-phospholipids, which deserve their own section and will be covered in Part 3 of this series.

Emerging technologies

New poly(amino acid) polymers incorporating non-canonical amino acids have a bright future in the field of polymeric nanoparticles. Lubrizol’s Apisolex is an amphiphilic di-block copolymer comprised of poly(sarcosine) as the hydrophilic block, and block of L-tyrosine and the D-enantiomer of leucine as the hydrophobic block. Since it is a poly(amino acid), it retains the non-immunogenic and biocompatible properties of naturally occurring peptides, but the use of D-leucine in parts enhanced drug solubilizing properties—50,000-fold increase of BCS class II and IV APIs.