In vitrostudies on 5-florouracil-loaded DTPA-PE containing nanosized pegylated liposomes for diagnosis and treatment of tumor

Abstract

Theranostic liposomes carry both the therapeutic active ingredients and the contrast agent into one delivery system. Codelivery of imaging contrast agent and chemotherapeutic drugs can provide real-time validation of the targeting strategy, resulting in an another step forward for individual-based therapy. The aim of this study was the incorporation of different drugs used in the diagnosis and treatment of tumors into one delivery system to develop nanosized, polyethylene glycol (PEG)-coated, different charged theranostic liposomes. Different charged liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or Phospholipon(®) 90G (PL 90G; Phospholipid GmbH, Cologne, Germany), cholesterol, poly(ethylene glycol)2000/phosphatidyl ethanolamine (PEG(2000)-PE), stearylamine (SA) or dicetyl phosphate (DCP), and diethylenetriamine pentaacetate/PE (DTPA-PE) as bilayer ingredients and 5-florouracil (5-FU) as active substance were prepared by the film technique. Characterization, 5-FU in vitro release, cytotoxicity, and physical stability studies were performed. Particle size of all liposomes was 100-150 nm. Difference was not noted between encapsulation efficiency (EE%) of neutral DPPC and PL 90G liposomes containing 5-FU. EE% of charged DPPC liposomes was higher than that of charged PL 90G liposomes. PL 90G containing liposomes had a higher phospholipid amount than the same formulation of DPPC liposomes. DPPC containing different charged liposomes were selected for cytotoxicity studies. Different charged DPPC liposomes had the same antitumoral activity with the free 5-FU solution on MCF-7 cell lines. Liposome dispersions were more stable from the point of particle-size change and 5-FU leakage during storage at refrigerated temperature. The results of this study are very encouraging for the development of theranostic liposome formulations as a targeted delivery system for drugs, such as 5-FU, used both in therapy and imaging.

Dynamic, Nonsink Method for the Simultaneous Determination of Drug Permeability and Binding Coefficients in Liposomes

“…Meanwhile, the nanoparticles remain concentrated within the small volume compartment and separated from the reservoir by a semipermeable membrane. 4 , 8 , 9 , 15 − 18 Unfortunately, a large reservoir volume does not ensure sink conditions within the dialysis chamber itself. Depending on the nanoparticle release kinetics and the extent of drug binding to the nanoparticle, transport across the dialysis membrane may become rate-limiting.…”

“…Dynamic dialysis uses a large reservoir in an attempt to provide the sink conditions necessary to drive drug release to completion. Meanwhile, the nanoparticles remain concentrated within the small volume compartment and separated from the reservoir by a semipermeable membrane. ,,,− Unfortunately, a large reservoir volume does not ensure sink conditions within the dialysis chamber itself. Depending on the nanoparticle release kinetics and the extent of drug binding to the nanoparticle, transport across the dialysis membrane may become rate-limiting. , Corrections for drug binding to the nanoparticles and the barrier properties of the dialysis membrane are therefore crucial when employing dynamic dialysis for predictive modeling. ,,, In some cases, incomplete release has been observed even though approximate sink conditions (based on overall drug concentration gradients) were maintained due to factors such as pH differences or drug binding phenomena.…”

68Ga‐labeled, imatinib encapsulated, theranostic liposomes: Formulation, characterization, and in vitro evaluation of anticancer activity

“…In addition, liposomes could be directly radiolabeled with 68 Ga by the addition of DTPA-PE at the preparation phase of liposomes (Varani et al, 2022). Although lower amount of DTPA-PE (0.1%-7% mol lipid −1 ) was added to the liposome formulation in the literature, that formulations were radiolabeled with Tc 99m or In 111 unlike this study (Liko et al, 2013;Silindir et al, 2013;Whiteman et al, 2001). To obtain stabile 68 G8 radiolabeled liposomes, the concentration of DTPA-PE was chosen as 10% mol lipid −1 .…”