Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
28
4
2011
Possible Role of Epidermal Growth Factor Receptors in the Therapy of Pancreatic Cancer
293-356
10.1615/CritRevTherDrugCarrierSyst.v28.i4.10
Sahil
Aggarwal
Nanomedicine Research Center, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142 001 (PB), India
Swati
Gupta
Nanomedicine Research Center, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142 001 (PB), India; Department of Pharmaceutical Sciences, University of South Florida Health, Tampa, FL, 33612, USA
Manish K.
Gupta
Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Chemistry, I.S.F. College of Pharmacy, Moga 142 001 (PB), India
R. S. R.
Murthy
Nanomedicine Research Center, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142 001 (PB), India
Suresh P.
Vyas
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar, M. P., India, 470003
active targeting
endocytosis
epidermal growth factor receptor
pancreatic cancer
passive targeting
receptor signaling
Pancreatic cancer is considered an 'orphan' cancer because of its relative low incidence. Unfortunately, even with early diagnosis, mortality rates are high and it ranks eighth in the worldwide ranking of deaths due to cancer. The administration of chemotherapeutic agents for the treatment of advanced disease has failed, and current research focuses on the understanding of molecular pathways in order to investigate the role of targeted therapy. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways of various growth factors, among which the epidermal growth factor receptor (EGFR) plays an important role. Growth factor receptors and their ligands not only regulate normal cell processes, but have also been identified as key regulators of human cancer formation. EGFR has been found to be expressed and altered in pancreatic cancer and clearly plays a significant role in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis, and metastatic spread. The amplitude and kinetics of growth factor signaling are determined mainly by a highly regulated endocytic process that sorts and directs activated receptors to degradation in lysosomes. Therefore, EGFR is a legitimate therapeutic target. The aim of this review is to outline the endocytic escape of EGFRs in cancer with special attention towards recent advances in various approaches adopted for EGFR targeting.
Lipid Nanocarriers: Influence of Lipids on Product Development and Pharmacokinetics
357-393
10.1615/CritRevTherDrugCarrierSyst.v28.i4.20
Kamla
Pathak
Department of Pharmaceutics, Rajiv Academy for Pharmacy, P.O.Chhattikara, Mathura, INDIA
Lav
Keshri
Department of Pharmaceutics, Rajiv Academy for Pharmacy, P.O. Chhatikara, Mathura, India
Mayank
Shah
Department of Pharmaceutics, Rajiv Academy for Pharmacy, P.O. Chhatikara, Mathura, India
solid lipid nanoparticles
SLN
nanostructured lipid carriers
NLC
pharmacosomes
lipid drug conjugates
LDC
product development
pharmacokinetics
Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.