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JournalISSN: 0743-4863

Critical Reviews in Therapeutic Drug Carrier Systems 

Begell House
About: Critical Reviews in Therapeutic Drug Carrier Systems is an academic journal published by Begell House. The journal publishes majorly in the area(s): Drug delivery & Drug carrier. It has an ISSN identifier of 0743-4863. Over the lifetime, 465 publications have been published receiving 36324 citations. The journal is also known as: C.R.C. critical reviews in therapeutic drug carrier systems & Chemical Rubber Company critical reviews in therapeutic drug carrier systems.


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TL;DR: This review will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery, including a review of current activities in the field of liposomes, and challenging issues of targeting and triggering will be discussed in detail.
Abstract: In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.

768 citations

Journal Article
TL;DR: PEG-modified cytokines have been constructed and one of the conjugates, PEG- modified granulocyte-macrophage colony-stimulating factor, showed dissociation of two biological properties, which may open new horizons to the application of PEGylation technology.
Abstract: Poly(ethylene glycol) (PEG) is a water soluble polymer that when covalently linked to proteins, alters their properties in ways that extend their potential uses. PEG-modified conjugates are being exploited in many different fields. The improved pharmacological performance of PEG-proteins when compared with their unmodified counterparts prompted the development of this type of conjugate as a therapeutic agent. Enzyme deficiencies for which therapy with the native enzyme was inefficient (due to rapid clearance and/or immunological reactions) can now be treated with equivalent PEG-enzymes. PEG-adenosine deaminase has already obtained FDA approval. PEG-modified cytokines have been constructed and, interestingly, one of the conjugates, PEG-modified granulocyte-macrophage colony-stimulating factor, showed dissociation of two biological properties. This novel observation may open new horizons to the application of PEGylation technology. The biotechnology industry has also found PEG-proteins very useful because PEG-enzymes can act as catalysts in organic solvents, thereby opening the possibility of producing desired stereoisomers, as opposed to the racemic mixture usually obtained in classical organic synthesis. Covalent attachment of PEG to proteins requires activation of the hydroxyl terminal group of the polymer with a suitable leaving group that can be displaced by nucleophilic attack of the epsilon-amino terminal of lysine residues (other nucleophilic groups can also interact). Several chemical groups have been exploited to activate PEG, thereby giving rise to a variety of PEG-proteins. Some of these varieties retain part of the activating group as a coupling moiety between PEG and protein and others provide a direct linkage. For each particular application, different coupling methods provide distinct advantages.(ABSTRACT TRUNCATED AT 250 WORDS)

718 citations

Journal Article
TL;DR: Predicting a priori the alteration of pharmaceutical properties caused by the three degradation routes is difficult, and must be determined on a case-by-case basis for each protein.
Abstract: The biochemical literature has been surveyed to present an overview of the three most common protein degradation pathways: protein aggregation, deamidation, and oxidation. The mechanisms for each of these degradation routes are discussed with particular attention given to the effect of formulation conditions such as pH, ionic strength, temperature, and buffer composition. Strategies to reduce protein degradation are also discussed. These strategies are based on an understanding of the degradation mechanisms and the effect of changes in the storage conditions and formulation components on the degradation. The effects of each of the degradation routes on pharmaceutically relevant properties such as biological activity, metabolic half-life, and immunogenicity are summarized. Predicting a priori the alteration of pharmaceutical properties caused by the three degradation routes is difficult, and must be determined on a case-by-case basis for each protein. The difficulty in predicting the effect of degradation and analyzing the temperature dependence of reaction rates in proteins results in longer development times for protein formulations than for small molecule formulations. Although the use of accelerated stability to predict protein shelf life is difficult, conditions are discussed whereby the Arrhenius equation can be used to shorten formulation development time.

708 citations

Journal ArticleDOI
TL;DR: The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants.
Abstract: Nanoparticles represent drug delivery systems suitable for most administration routes. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA), Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively investigated because of their biocompatibility and biodegradability. Nanoparticles act as potential carries for several classes of drugs such as anticancer agents, antihypertensive agents, immunomodulators, and hormones; and macromolecules such as nucleic acids, proteins, peptides, and antibodies. The options available for preparation have increased with advances in traditional methods, and many novel techniques for preparation of drug-loaded nanoparticles are being developed and refined. The various methods used for preparation of nanoparticles with their advantages and limitations have been discussed. The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants. Nanoparticles can be designed for the site-specific delivery of drugs. The targeting capability of nanoparticles is influenced by particle size, surface charge, surface modification, and hydrophobicity. Finally, the performance of nanoparticles in vivo is influenced by morphological characteristics, surface chemistry, and molecular weight. Careful design of these delivery systems with respect to target and route of administration may solve some of the problems faced by new classes of active molecules.

699 citations

Journal Article
TL;DR: Results of recent studies are brought together which describe how liposomal stability and clearance in vivo are controlled by the architecture of the vesicles themselves which in turn, via interaction with humoral factors, controls the fate in terms of tissue distribution of the carrier and its contents.
Abstract: Of fundamental importance in the design of a therapeutic drug carrier system is a thorough understanding of the factors which control its fate in the living animal. The use of liposomes as a carrier system able to improve the therapeutic efficacy of a wide range of drugs, requires manipulation of its physical characteristics, thereby influencing in vivo behavior. This review brings together findings of recent studies which describe how liposomal stability and clearance in vivo are controlled by the architecture of the vesicles themselves which in turn, via interaction with humoral factors, controls the fate in terms of tissue distribution of the carrier and its contents. Based on these studies, a rationale for liposome design aimed at in vivo drug delivery is discussed.

587 citations

Performance
Metrics
No. of papers from the Journal in previous years
YearPapers
202322
202224
20216
202011
201913
201812