Poloxamer

About: Poloxamer is a research topic. Over the lifetime, 1477 publications have been published within this topic receiving 53944 citations.

Biodegradable block copolymers as injectable drug-delivery systems

Abstract: Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 degrees C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.

Micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers in aqueous solutions: Thermodynamics of copolymer association

Abstract: The critical micellization temperature (cmt) and critical micellization concentration (cmc) values of 12 Pluronic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, covering a wide range of molecular weights (2,900--14,600) and PPO/PEO ratios (0.19--1.79), were determined employing a dye solubilization method. A closed association model was found to describe adequately the copolymer micellization process for the majority of the Pluronics and used to obtain the standard free energies ([Delta]G[degree]), enthalpies ([Delta]H[degree]), and entropies ([Delta]S[degree]) of micellization. It was determined that the micellization process is entropy-driven and has an endothermic micellization enthalpy. The hydrophobic part of the Pluronics, PPO, was responsible for the micellization, apparently due to diminishing hydrogen bonding between water and PPO with increasing temperature. The cmc dependence on temperature and size of headgroup (PEO) of Pluronics follows a similar trend with lower molecular weight C[sub i]E[sub j] nonionic surfactants, the effect of temperature being more pronounced with the Pluronics. The PEO-PPO-PEO block copolymers were compared to PPO-PEO-PPO block and PEO-PPO random copolymers, in an attempt to probe the effect of molecular architecture in the formation of micelles. No micelles were observed in aqueous PPO-PEO-PPO block copolymer solutions with increasing temperature, up to the cloud point.

A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics

Abstract: Poloxamer 407 copolymer (ethylene oxide and propylene oxide blocks) shows thermoreversible properties, which is of the utmost interest in optimising drug formulation (fluid state at room temperature facilitating administration and gel state above sol-gel transition temperature at body temperature promoting prolonged release of pharmacological agents). Pharmaceutical evaluation consists in determining the rheological behaviour (flow curve or oscillatory studies), sol-gel transition temperature, in vitro drug release using either synthetic or physiological membrane and (bio)adhesion characteristics. Poloxamer 407 formulations led to enhanced solubilisation of poorly water-soluble drugs and prolonged release profile for many galenic applications (e.g., oral, rectal, topical, ophthalmic, nasal and injectable preparations) but did not clearly show any relevant advantages when used alone. Combination with other excipients like Poloxamer 188 or mucoadhesive polymers promotes Poloxamer 407 action by optimising sol-gel transition temperature or increasing bioadhesive properties. Inclusion of liposomes or micro(nano)particles in Poloxamer 407 formulations offers interesting prospects, as well. Besides these promising data, Poloxamer 407 has been held responsible for lipidic profile alteration and possible renal toxicity, which compromises its development for parenteral applications. In addition, new findings have demonstrated immuno-modulation and cytotoxicity-promoting properties of Poloxamer 407 revealing significant pharmacological interest and, hence, human trials are in progress to specify these potential applications.