Liposomes as MR contrast agents: Pros and cons

Abstract

Liposomes are generally thought of as being useful for entrapping drugs within their internal aqueous space. When used with MR contrast agents, this has the drawback that water flux across the membrane bilayer is limiting to contrast enhancement. This can be partially overcome by making the liposomes very small, such that surface area is relatively great compared to internal volume, thereby facilitating water exchange. Alternatively the membranes can be designed to be permeable to water but this may render the vesicles unstable in serum. Another approach is to incorporate the contrast agents into the lipid bilayer. By designing novel complexes of manganese with the ligands incorporated onto dual acyl chains, we have achieved R1 and R2 values of over 20/mmol sec-1 or more than five times higher than Gd-DTPA. Hepatic metastasis detection is significantly improved in rats at doses of only 10 mumol/kg manganese. Membrane-bound manganese complexes function as highly effective liver imaging agents and merit further study for development as agents to undergo human clinical trials.

MR imaging of biodegradable polymeric microparticles: A potential method of monitoring local drug delivery

“…The bioadhesive properties of the microparticles prevent them from being easily voided, and allow any encapsulated drug to be situated near diseased cells and have increased bioavailability locally. Furthermore, the overall stability of these polymeric microparticles in vivo is an advantage over other delivery vehicles, such as liposomes, that may be more easily metabolized in vivo (17). The Nile Red dye used in these experiments can be considered as a substitute model for other hydrophobic therapeutic compounds that may be encapsulated with Gd-DTPA in the microparticles simultaneously.…”

Enhanced tumor MR imaging with gadolinium‐loaded polychelating polymer‐containing tumor‐targeted liposomes

“…A disadvantage of this approach is the leakage of low-molecular-weight compounds from the vesicles in vivo. Alternatively, liposomal contrast agents were prepared using membraneincorporated reporter metal-loaded chelating agents such as Gd-DTPA-stearylamine (DTPA-SA), Gd-DTPAphosphatidyl ethanolamine (DTPA-PE), and amphiphilic acylated paramagnetic complexes of Mn and Gd (3)(4)(5). All these agents act by increasing longitudinal relaxation rates R1 of surrounding water protons, resulting in an increase of tissue signal intensity.…”

Predicted Drug Concentration Distribution Using a Validated Finite Element Model in Locally Advanced Breast Cancer

“…Prior MRI-based reports have focused on obtaining images in the RES (9)(10)(11)(12)(13)(14), which tends to concentrate liposomes following intravenous administration. When metal ions are retained inside liposomes, MR signal intensity is relatively unaffected (13,15), Shortening of T 1( for example, depends on interaction between metal ions and water (16). Because water cannot easily cross the lipid membrane except with specialized lipid formulations designed to be relatively unstable (15,16), signal intensity changes are low (13).…”

“…When metal ions are retained inside liposomes, MR signal intensity is relatively unaffected (13,15), Shortening of T 1( for example, depends on interaction between metal ions and water (16). Because water cannot easily cross the lipid membrane except with specialized lipid formulations designed to be relatively unstable (15,16), signal intensity changes are low (13). An alternative has been to attach paramagnetic metals to the outer liposome surface (13,15).…”

“…Because water cannot easily cross the lipid membrane except with specialized lipid formulations designed to be relatively unstable (15,16), signal intensity changes are low (13). An alternative has been to attach paramagnetic metals to the outer liposome surface (13,15). These surface attached contrast agents have shown 1\ shortening essentially equivalent to that of free ions.…”