Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
34
3
2017
Three- and Four-Dimensional Spheroid and FiSS Tumoroid Cultures: Platforms for Drug Discovery and Development and Translational Research
185-208
10.1615/CritRevTherDrugCarrierSyst.2017018042
R. R.
Nair
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; Transgenex Nanobiotech Inc., Tampa, FL 33612, USA
S.
Padhee
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; Transgenex Nanobiotech Inc., Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
T.
Das
Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
R.
Green
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
M.
Howell
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
S. S.
Mohapatra
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Departments of Internal Medicine, University of South Florida, Tampa, FL 33612, USA; James A. Haley VA Hospital, Tampa, FL, 33612, USA
Subhra
Mohapatra
Center for Research and Education in Nanobioengineering, University of South Florida, Tampa, FL 33612, USA; Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA; James A. Haley VA Hospital, Tampa, FL, 33612, USA
2D cultures
3D cultures
4D cultures
biopsy-derived tumoroids (BdTs)
cancer stem cells (CSCs)
extracellular matrix (ECM)
fiber-inspired smart scaffold (FiSS)
tumor microenvironment (TME)
There have been remarkable improvements in our understanding of cancer biology. However, therapeutic improvements, with a few exceptions, have been minimal. Also, significant
challenges remain in translating fundamental discoveries in cancer biology and genetics into effective drugs and cures. Traditional two-dimensional monolayer cell cultures lack predictive value, resulting in a >90% failure rate of compounds in clinical trials. A developing cancer is a symbiotic tissue consisting of cancer cells, including cancer stem cells (CSCs), and cohabitating
with the components of its environment to form a tumor microenvironment (TME) niche. Throughout the process of tumorigenesis, ubiquitous autocrine and paracrine signaling between the cellular and noncellular components of the TME dictates the milieu and structure of this niche. Arising out of such interactions are the cancer cell's phenotypic characteristics, such as stemness, epithelial mesenchymal transformation (EMT), and drug resistance which in turn greatly affect the response of these cells to drug therapy. For these reasons, in order to delineate the mechanism
of tumorigenesis and in the process discover drugs that will have greatest impact on tumor growth, it becomes imperative to study the cancer cell in context of its microenvironment. In the present review, we enumerate the advantages of three- and four-dimensional (3D and 4D) cell cultures and describe the various cell culture platforms that are being used to study tumorigenesis in vitro. These culture systems will not only aid in the study of tumor progression complexities in a cost-effective and rapid manner; they also are expected to facilitate the discovery and delivery of therapeutic regimens that will have more success making it to the clinic.
Stimuli-Responsive Systems with Diverse Drug Delivery and Biomedical Applications: Recent Updates and Mechanistic Pathways
209-255
10.1615/CritRevTherDrugCarrierSyst.2017017284
Bhupinder
Singh
Professor
Rajneet Kaur
Khurana
University Grants Commission Centre of Advanced Studies, University Institute of Pharmaceutical
Sciences, Panjab University, Chandigarh, India
Babita
Garg
University Grants Commission Centre of Advanced Studies, University Institute of Pharmaceutical
Sciences, Panjab University, Chandigarh, India
Sumant
Saini
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India 160014
Ranjot
Kaur
University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab
University, Chandigarh, India 160014; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom
hydrogels
intelligent polymers
in situ gelling
smart polymers
sol-to-gel
theranostic
molecular imprinting
With the advent of "intelligent" polymeric systems, the use of stimuli-responsive in situ gelling systems has been revolutionized. These interesting polymers exist as free-flowing aqueous solutions before administration and undergo a phase transition to form a viscoelastic gel in a physiological environ through various stimuli such as temperature, pH, solvent, biochemical, magnetic, electric, ultrasound, and photo-polymerization. These smart polymers are endowed with numerous merits such as ease of administration, sustained release, reduced frequent administration with improved patient compliance, and targeted and spatial delivery of a drug with reduced
frequency of side effects. Concerted efforts are being made to modify these polymers synthetically because they hold immense potential in various fields such as polymer chemistry, materials science, pharmaceutics, bioengineering medicine, and chemical engineering. In addition to novel
drug delivery, these smart polymeric systems have exhibited tremendous applications in tissue engineering, regenerative biomedicine, molecular imprinting, cancer therapy, gene delivery, theranostic and other applications. The current review mainly focuses on the fundamental principles
involved during in situ gelling, use of various "smart" drug-delivery formulation systems through diverse routes for their administration, as well as their well-documented biomedical applications. The pertinent literature, marketed formulations, and recent advances on these stimuli-responsive sol−gel-transforming systems are also discussed.
Lipid Nanoparticles for Nasal/Intranasal Drug Delivery
257-282
10.1615/CritRevTherDrugCarrierSyst.2017018693
S.
Cunha
UCIBIO, ReQuimTe, Laboratory of Pharmaceutical Technology/Centre of Research
in Pharmaceutical Sciences, Faculty of Pharmacy, Porto University, Porto, Portugal
M. H.
Amaral
UCIBIO, ReQuimTe, Laboratory of Pharmaceutical Technology/Centre of Research
in Pharmaceutical Sciences, Faculty of Pharmacy, Porto University, Porto, Portugal
J. M. Sousa
Lobo
UCIBIO, ReQuimTe, Laboratory of Pharmaceutical Technology/Centre of Research
in Pharmaceutical Sciences, Faculty of Pharmacy, Porto University, Porto, Portugal
Ana
Silva
University Fernando Pessoa
drug delivery
nanostructured lipid carriers
nasal/intranasal administration
solid lipid nanoparticles
Studies on the development of drug delivery systems have increased because these systems have particular characteristics that allow them to improve therapeutics. Among these, lipid nanoparticles (solid lipid nanoparticles, SLNs; and nanostructured lipid carriers, NLCs) have
demonstrated suitability for drug targeting. The nasal administration of drug-loaded lipid nanoparticles showed effectiveness in treating central nervous system (CNS) disorders, particularly neurodegenerative diseases, because the nasal route (also called intranasal route) allows direct
nose-to-brain drug delivery by means of lipid nanoparticles. Nonetheless, the feasibility of this application remains an open field for researchers. Drawbacks must be overcome before reaching the clinic (e.g., drug absorption at subtherapeutic levels, rapid mucociliary clearance). The intranasal administration of drugs for systemic absorption is effective for treating other conditions, such as cardiovascular diseases, infections, severe pain, and menopausal syndrome. In the near future, it is expected that patients will benefit from the advantages of lipid nanoparticle–based formulations, via the nasal/intranasal route, which bypasses the blood-brain barrier (BBB), avoiding first-pass metabolism and gastrointestinal degradation. This review discusses the use of SLNs and NLCs for nasal drug administration. A brief description
of the nasal route and the features of SLNs and NLCs is initially provided.