Applications of Nanosystems to Anticancer Drug Therapy (Part II. Dendrimers, Micelles, Lipid-based Nanosystems)

Abstract

The great efforts of many researchers have brought down some of the barriers that exist to turn a good in vitro compound into a potential in vivo drug. The advent of pharmaceutical nanotechnology has allowed an arsenal of drugs with poor stability, low solubility, high off-target toxicity and other disadvantageous features, to be accessible as pharmaceutical products that could be administered to a patient. Nanotechnology was introduced in drug delivery very long ago, but has flourished with unprecedented intensity during the last twenty years and now a diversity of nano-based preparations are at clinical stage of development or already available in the market. Undoubtedly, nanotechnology plays a key role in future pharmaceutical development and pharmacotherapy. In the first part of this review, we have already discussed recent (2008-2012) patents on linear polymer-based nanosystems (nanogels, nanospheres and nanocapsules) applications to cancer therapy. Here, we have expanded such analysis to branched polymers (dendrimers), self-assembling nanomicelles and lipid-based nanocarriers.

Regulatory aspects on nanomedicines

“…However, different classes of proposed nanomedicines such as quantum dots, dendrimers, and carbon nanotubes have brought additional concerns. The clinical use of these new products might be indeed compromised for many years, related to their potential toxicity and immunological deleterious effects [21,22,23,24,25,26].…”

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

“…9 Dendrimers offer unique opportunities in the synthesis of agents with broadspectrum anti-HIV-1 activity and activity against Alzheimer's disease, herpes simplex virus (HSV), bacteria, and cancer. [10][11][12][13][14] A group of dendrimers with a carbosilane structure has demonstrated potential against HIV and other pathogens. These dendrimers are particularly suitable for this application due to the simplicity of their synthesis, which allows for large amounts of the polymer to be generated; the ability to obtain a polymer with a defined molecular weight and number of terminal functions; chemical and biochemical stability; biologically inertness; and the low polarity of the C-Si bond, which imparts hydrophobicity to the carbosilane scaffold.…”

Regulatory Aspects of Oncologicals: Nanosystems Main Challenges

“…As a result, it would normally allow the use of considerable lower doses of active pharmaceutical ingredients (API), increasing their therapeutic index and improving their safety profi le (Moghimi et al 2012 ). Even though, new classes of proposed nanopharmaceuticals, as dendrimers (Tekade et al 2008 ;Ruiz et al 2014 ), carbon nanotubes (Bianco et al 2005a , b ;Wang et al 2013 ) or quantum dots (Reiss et al 2009 ;Cai and Chen 2008 ), have given rise to additional concerns related to the use of those novel materials at human level, namely to their potential immunological deleterious effects, and will probably be absent from any clinical use at least for many years.…”

“…Nowadays, amphiphilic materials composed of block copolymers (generally di-and triblock-copolymers) or polymers conjugated with lipids or phospholipids are largely used (Torchilin 2007 ). Anticancer agents-loaded micelles, namely including paclitaxel, doxorubicin, camptothecin or cisplatin derivatives, are currently in phase II clinical trials showing their potential as drug carriers (Schütz et al 2013 ;Ruiz et al 2014 ). With the extensive number of PEG-block-copolymers being developed, it is expected an increased industry desire to foster their translation to clinic.…”

“…poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE), polylactide-poly(ethylene glycol) (PLA-PEG), will allow the binding of a variety of targeting moieties potentiating both combined and selective therapies (Ruiz et al 2014 ;Torchilin 2009 ).…”