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Gemcitabine is widely used for anticancer therapy. However, its short blood circulation time and poor stability greatly impair its application. To solve this problem, we prepared a poly (L-glutamic acid)-g-methoxy poly (ethylene glycol)-gemcitabine conjugate (L-Gem) with a 14.3 wt% drug-loading content. L-Gem showed concentration- and time-dependent cytotoxicity towards 4T1, LLC, MIA PaCa-2 and A2780 in vitro. Pharmacokinetic and biodistribution studies indicated that L-Gem had remarkably enhanced blood stability, prolonged blood circulation time and greatly improved selective tumor distribution compared with free gemcitabine. The area under the concentration-time curve from zero to infinity [AUC] of L-Gem in plasma was 43-fold higher than that of free gemcitabine. The AUC of the inactive metabolite, 2́-deoxy-2́, 2́-difluorouridine in the L-Gem group was ∼20% of that observed in the free gemcitabine group. The drug tumor accumulation ratio in the L-Gem group relative to the free gemcitabine group was 9.9 at 36 h, while the tumor AUC ratio was 15.8. Testing on Balb/C mice bearing the 4T1 tumor further demonstrated that L-Gem had significantly higher anticancer efficacy than free gemcitabine in vivo. These findings indicated that L-Gem has great potential for cancer treatment.
This article was published in the following journal.
Name: International journal of pharmaceutics
Herein we demonstrate the formation of stereocomplex prodrugs of oligo(L-lactic acid)-gemcitabine (o(LLA)-GEM) and oligo(D-lactic acid)-gemcitabine (o(DLA)-GEM) for stable incorporation in poly(ethyle...
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A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.
A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins.
The addition of a tail of polyadenylic acid (POLY A) to the 3' end of mRNA (RNA, MESSENGER). Polyadenylation involves recognizing the processing site signal, (AAUAAA), and cleaving of the mRNA to create a 3' OH terminal end to which poly A polymerase (POLYNUCLEOTIDE ADENYLYLTRANSFERASE) adds 60-200 adenylate residues. The 3' end processing of some messenger RNAs, such as histone mRNA, is carried out by a different process that does not include the addition of poly A as described here.
A poly(ADP-ribose) polymerase that contains two ZINC FINGERS in its N-terminal DNA-binding region. It modifies NUCLEAR PROTEINS involved in chromatin architecture and BASE EXCISION REPAIR with POLY ADENOSINE DIPHOSPHATE RIBOSE.
A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...