PEGylation, successful approach to drug delivery.
TL;DR: Polyethylene glycol-drug conjugates have several advantages: a prolonged residence in body, a decreased degradation by metabolic enzymes and a reduction or elimination of protein immunogenicity.
About: This article is published in Drug Discovery Today.The article was published on 2005-11-01. It has received 2138 citations till now. The article focuses on the topics: PEGylation & Drug delivery.
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TL;DR: This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use and demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles.
3,189 citations
TL;DR: PEG is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery and alternative polymers will be evaluated.
Abstract: Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.
2,815 citations
TL;DR: The bioorthogonal chemical reactions developed to date are described and how they can be used to study biomolecules.
Abstract: The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.
2,537 citations
TL;DR: The in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure.
Abstract: In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.
2,251 citations
TL;DR: In this paper, the potential of lignocellulosic biomass as an alternative platform to fossil resources has been analyzed and a critical review provides insights into the potential for LBS.
1,763 citations
References
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TL;DR: The basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor.
5,955 citations
TL;DR: Although the use of PP inhibitors shows that there is significant basal PP activity in cells, it has become apparent that the activities of PPs are regulated in a sophisticated manner by a combination of targeting and regulatory subunits and by specific inhibitors.
2,863 citations
TL;DR: The modified bovine serum albumins showed substantial changes in properties, such as solubility, electrophoretic mobility in acrylamide gel, ion exchange chromatography, and sedimentation, as compared with the unmodified protein.
1,349 citations
TL;DR: Methoxypolyethylene glycols and catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections and no evidence of tissue or organ damage was seen.
1,261 citations
TL;DR: Treatment of patients who have acromegaly with pegvisomant with a growth hormone–receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
Abstract: Background Patients with acromegaly are treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone–receptor antagonist that blocks the action of growth hormone. Methods We conducted a 12-week, randomized, double-blind study of three different daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. Results The mean (±SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0±16.8 percent in the placebo group, 26.7± 27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1±26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5±21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score for total symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P«0.05). The incidence of adverse effects was similar in all groups. Conclusions On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone–receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. (N Engl J Med 2000;342:1171-7.)
757 citations