Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
27
3
2010
Potential Approaches for Drug Delivery to the Brain: Past, Present, and Future
187-236
10.1615/CritRevTherDrugCarrierSyst.v27.i3.10
Vandana
Soni
Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, Madhya Pradesh, India, Pin-470003
Anekant
Jain
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar-470 003 (MP)
Piush
Khare
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar-470 003, (MP), India
Arvind
Gulbake
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar (M. P.) 470003, India
Sanjay Kumar
Jain
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar (M.P.), India
blood–brain barrier
permeability
brain tumor
prodrugs
The objective of this article is to provide the reader with an update on some research highlights from the past to the present, as well as future possibilities to achieve improved delivery of drugs across the blood–brain barrier (BBB). In the past, dye studies confirmed the presence of the BBB and blood–cerebrospinal fluid barriers, which seem to play a major role in transporting drug molecules for the treatment of life-threatening diseases such as brain cancer and Alzheimer's. Presently, transportation mechanisms such as simple diffusion, carrier-mediated, absorptive-mediated, and receptor-mediated transcytosis are extensively used for BBB uptake of drug molecules. The spectrum of future neuropharmaceuticals falling into these categories ranges from peptides to nucleotide-based drugs as well as gene and stem cell deli very agents, and is increasing at a rapid rate with promising results. There has also been considerable progress in the development of quantitative methods to examine BBB permeability in humans and animals. Currently, intravenous administration and in situ brain perfusion techniques are the most versatile and sensitive methods to measure transport into the brain. This article also reviews the various methodologies available for assessing the transfer of drug molecules undergoing significant uptake through the BBB in vivo.
Gemini Amphiphiles: A Novel Class of Nonviral Gene Delivery Vectors
237-278
10.1615/CritRevTherDrugCarrierSyst.v27.i3.20
Mukesh
Kumar
Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat
Kaustubh
Jinturkar
Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat
M.R.
Yadav
Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara, Gujarat
Ambikanandan
Misra
Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Post Box No. 51, Kalabhavan, Vadodara 390001 Gujarat, India
nonviral vectors
gemini surfactant
gemini lipid
gene delivery
transfection
A number of carriers have been developed for the delivery of genes, but the search for a clinically successful ideal carrier is ongoing. Nonviral carriers, especially cationic liposomes, were developed to resolve issues related to the immunogenicity and oncogenicity of viral carriers. Many synthetic cationic amphiphiles have been synthesized and structurally modified to incorporate genes into vesicular carriers to enhance DNA transfection efficiency and to reduce carrier toxicity. Of these carriers, gemini amphiphiles have demonstrated the suitable physiochemical properties needed for promising and novel gene carriers. Moreover, three basic parts (head, spacer, and chain) in the structure of gemini amphiphiles provide ample opportunities to tailor them according to the needs of specific gene delivery. Initial studies have demonstrated the superiority of gemini amphiphiles in gene delivery efficiency over currently used carriers for gene delivery. This article critically reviews these studies and provides a balanced view to fellow scientists to carry out their efforts in filling in the technological gaps.