This review describes block copolymer-based systems that are used in drug formulation development. The use of amphiphilic block copolymers to modify pharmacological performance of various classes of drugs attracts more and more attention. This is largely attributable to the high tendency of block copolymer-based drug formulations to self-assemble, as well as flexibility of block copolymer chemistry, which allows precise tailoring of the carrier to virtually any chemical entity. Combination of these features allows adjustment of block copolymer-based drug formulations to achieve the most beneficial balance in drug biological interactions with the systems that control its circulation in and removal from the body and its therapeutic activity. The following major aspects are considered: 1) physical properties of formulations and the methods used to adjust these properties towards the highest pharmacological performance of the product; 2) combinatorial methods for optimisation of block copolymer-based formulations; 3) biological response modifying properties of block copolymer-based formulations.
At the present, a high potential of epigallocatechin-3-gallate (EGCG) as a new preventive and therapeutic agent in oncology and several other indications is well established. EGCG exerts its antitumor activity through induction of cell cycle arrest and apoptosis, inhibition of tumor angiogenesis, migration, and metastasisdue to its ability to interact with multiple targets in cancer cell. Unfortunately, very low oral bioavailability of EGCG prevents its efficient development as novel medicine. In this work, we have developed a polymer based nano-formulation of EGCG that significantly improved its oral bioavailability by increasing systemic exposure of the compound by about8-fold. This formulation comprises a well-known inactive ingredient non-ionic blockcopolymer Pluronic F127 that has recently been successfully used to increase bioavailability of another promising phytonutrient, 3,3`-diindolylmethane. The pharmacokinetic parameters established in the present study revealed that AUC and C max of the new formulation dosed at 500 mg/kg were 578.5 ± 73.8 µg•h/mL and 49.3 ± 2.9 µg/mL, while in the case of control EGCG administered in the equivalent dose AUC and C max were 72.9 ± 14.7 µg•h/mL, and 10.7 ± 1.1 µg/mL.
This study was undertaken towards enabling PET imaging of polymerbased drug delivery. Iodinated doxorubicin conjugate (DOXIB) was characterised against un-conjugated DOX within and outside a polymer formulation in tumour cell lines and tumour bearing animal models. The results provide the basis for developing the feasibility of [ '241]-DOXIB PET to assess in vivo pharmacokinetics of drug formulation.Introduction: Targeted drug delivery designed to enhance therapeutic index of anti-cancer chemotherapy has been demonstrated as a promising approach to maximise drug delivery to tumours and reducing normal tissue toxicity. SP1049C is a formulation of a non-covalentley incorporated DOX into micelles of polyoxypropylene-polyoxyethylene (POP-POE). In vivo, marked increases in tumour drug concentration were observed with SP1049C compared to DOX alone supporting the view that the polymer had the potential for DOX targeting. At present there is no ,,proof of principle" that such polymers may improve tumour and tissue targeting of cytotoxic drugs in humans. This study was undertaken towards developing DOXIB for PET imaging. We have prepared DOXIB and characterised its biophysical properties compared to that of DOX within the SP1049C formulation (see abstract, J Hadfield et al). In this study we evaluated, in vitro and in vivo, drug uptake in the.presence and absence of SP1049C carrier. Methods: Drug uptake was determined by incubating free DOX or DOXIB alone or in the presence of SP1049C carrier, with human breast carcinoma MCF-7 cells and their MDR MCF-7 DOX subline. Cell fluorescence was analysed by flow cytometry. Pharmacokinetic measurements were carried out in a Lewis lung carcinoma model. DOX (PBS), DOX (SP1049C), DOXIB (PBS) and DOXIB (SP1049C) were injected i.v. and at various times after injection, animals were sacrificed, and blood and turnour tissue samples were collected. Plasina aliquots were extracted with acetonitrile and NaCl was added to release anthracycline in the organic phase. Following evaporation, the dried samples were reconstituted in the HPLC mobile phase. Tumour homogenates were similarly extracted, analysed and drug concentrations were determined.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.