17 research outputs found
Synthetic Polymers as Drug-Delivery Vehicles in Medicine
Cancerous diseases present a formidable health problem worldwide. While the
chemotherapy of cancer, in conjunction with other treatment modalities, has reached a
significant level of maturity, efficacious use of such agents is still restricted by numerous
pharmacological deficiencies, such as poor water solubility, short serum circulation
lifetimes, and low bioavailability resulting from lack of affinity to cancer tissue and
inadequate mechanisms of cell entry. More critically still, most drugs suffer from toxic
side effects and a risk of drug resistance. The class of platinum anticancer drugs,
although outstandingly potent, is particularly notorious in that respect. Among the
countless methods developed in recent years in an effort to overcome these deficiencies,
the technology of polymer-drug conjugation stands out as a particularly advanced
treatment modality. The strategy involves the bioreversible binding, conjugating, of a
medicinal agent to a water-soluble macromolecular carrier. Following pharmacokinetic
pathways distinctly different from those of the common, nonpolymeric drugs, the
conjugate so obtained will act as a prodrug providing safe transport of the bioactive
agent to and into the affected, that is, cancerous cell for its ultimate cell-killing activity. The
present treatise will acquaint us with the pharmacological fundamentals of this drug
delivery approach, applied here specifically to the metalorganic platinum-type drug
systems and the organometallic ferrocene drug model. We will see just how this
technology leads to conjugates distinctly superior in antiproliferative activity to cisplatin,
a clinically used antitumor agent used here as a standard. Polymer-drug conjugation
involving metal-based and other medicinal agents has unquestionably matured to a
practical tool to the pharmaceutical scientist, and all indications point to an illustrious
career for this nascent drug delivery approach in the fight against cancer and other
human maladies
Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid
The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N′,N′-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH
< 7, the new carrier-drug conjugates that were obtained are well water-soluble
Dicyclopentadienyltitanium(IV) pyridine-2,6-dicarboxylate complexes : Synthesis and structural characterization as pentacoordinate titanocene derivatives
Reaction of (C5H5)2Ti(CH3)2 or (CH3)4C2(C5H4)2Ti(CH3)2 with pyridine-2,6-dicarboxylic acid (dipicolinic acid) yields titanocene dipicolinate derivatives. The molecular structure of (C5H5)2Ti dipicolinate is that of an axially symmetric, pentacoordinate titanocene derivative with two carboxyl oxygen atoms and the pyridine nitrogen atom as ligating atoms. Two identical chelate bite angles of only 71° make the dipicolinate ligand particularly suited to form a remarkably stable titanocene derivative with unprecedented pentacoordintae geometry