PEGylated Nanoliposomes Potentiated Oral Combination Therapy for Effective Cancer Treatment

Curr Drug Deliv. 2020;17(9):728-735. doi: 10.2174/1567201817666200724170708.

Abstract

The conventional treatment regimen for cancer with a single chemotherapeutic agent is far behind the clinical expectations due to the complexity of cancer biology and is also associated with poor Quality of Life (QOL) due to off-site toxicity and multidrug resistance. In recent years, nanopotentiated combination therapy has shown significant improvement in cancer treatment via a synergistic approach. However, being synthetic in nature, nanocarriers have been associated with the activation of the Complement (C) activation system resulting in serious hypersensitivity reactions known as CActivation Related Pseudoallergy (CARPA) effect once given via intravenous injection. On the other hand, nanopotentiated oral drug delivery offers several advantages for the effective and safe delivery of the drug to the target site. This hypothesis aims to put forward wherein Exemestane (chemotherapeutic agent) and lycopene (herbal bioactive) co-laden into PEGylated liposomes and delivered to the breast cancer via the oral route. PEGylation of the liposomes would prevent both molecules from the harsh microenvironment of the Gastrointestinal Tract (GIT) and would eventually promote their intestinal absorption via the lymphatic pathway to the systemic circulation. Lycopene being a potent antioxidant and anti-cancer herbal bioactive would promote the therapeutic efficacy of the Exemestane via a synergistic approach. This nanopotentiated oral combination therapy would pave the path for the safe and effective treatment of cancer.

Keywords: PEGylated liposome; breast cancer; combination therapy; exemestane; lycopene; oral drug delivery.

MeSH terms

  • Administration, Oral
  • Androstadienes / administration & dosage
  • Androstadienes / adverse effects
  • Androstadienes / pharmacokinetics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics*
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / pharmacokinetics
  • Biological Availability
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Cell Line, Tumor
  • Complement Activation / drug effects
  • Drug Synergism
  • Female
  • Gastrointestinal Absorption
  • Humans
  • Liposomes
  • Lycopene / administration & dosage
  • Lycopene / adverse effects
  • Lycopene / pharmacokinetics
  • Mice
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry
  • Proof of Concept Study
  • Tissue Distribution
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Xenograft Model Antitumor Assays

Substances

  • Androstadienes
  • Aromatase Inhibitors
  • Liposomes
  • Polyethylene Glycols
  • exemestane
  • Lycopene