L-lysine Citramide Research Articles

Uptake and Intracellular Distribution of 4-Aminofluorescein-Labelled Poly(L-Lysine Citramide Imide) in K562 Cells

4-Aminofluorescein (F1-NH2) was conjugated with various macromolecular carriers of the poly(L-lysine citramide)-type which were hydrophobised by ethyl (C2), heptyl (C7), and dodecyl (CI2) alky] groups attached to the pendent carboxyl of the lysine moieties present in repeating units. The dye was used to label the carriers and monitor their intracellular fate after introduction within the incubation medium of K562 cells. The labelled hydrophobised carriers formed multimolecular compacted aggregates stabilised by the balance of attractive hydrophobic interactions and repulsive electrostatic forces in the aqueous culture medium. The apparent molecular weights and the sizes of these aggregates were determined by Size Exclusion Chromatography (SEC) and by light scattering respectively. Comparison was made of the cell distribution of free and conjugated F1-NH2 in the cell cytoplasm and nucleus by using fluorescence microscopy and laser microspectrofluorometry. It was shown that cell uptakes resulted from adsorptive pinocytosis and depended on hydrophobicity and aggregation of the conjugates. The influence of physical entrapment of free-Fl-NH2 within the hydrophobic microdomains formed by aggregates F1-NH2 conjugates was also discussed.

Covalent Binding of Mannosyl Ligand via 6-O Position and Glycolic Arm to Target a PLCA-Type Degradable Drug Carrier toward Macrophages

Mononuclear phagocytes play a central role in the defense against important pathologies. Attempts were made to target drugs toward this cell type by using specific interactions between a mannose ligand and the lectin-type specific receptor present on the macrophage membrane. Basically, the use of a mannosyl radical as a homing device raised several problems: necessity to keep unmodified the part of the molecule which gives rise to lectin recognition, complex protection-deprotection chemistry, and blockage of the aldehyde function to preclude any side reaction. A new method was used to bind α-D-methylmannopy-ranoside, a commercially available precursor, through its primary hydroxyl group to the hydrosoluble bioresorbable drug carrier poly(L-lysine citramide imide). The method consisted of a few steps that did not require special protection of secondary hydroxyl groups. In the resulting conjugate, the pyranose structure of the sugar was retained. In vivo recognition of the conjugate by the lectin of mononuclear phagocytes was preserved.

Poly (L-Lysine Citramide), a Water-Soluble Bioresorbable Carrier for Drug Delivery: Aqueous Solution Properties of Hydrophobized Derivatives

Poly(L-lysine citramide) (PLCA), a novel biocompatible and bioresorbable water-soluble polymer, was designed as a macromolecular prodrug carrier coupling drugs to hydrophilic carriers generally leads to hydrophobization of the precursor macromolecules which then form micelle-like water-dispersed aggregates or are completely insoluble. To study these phenomena, hydrophobization of PLCA was investigated. Alkyl groups (C7 and C12) were covalently attached to the lysine of the polymer which was prepared by either step-growth polymerization or selective hydrolysis of alkylated derivatives. Hydrophobized macromolecules formed nanosized multimolecular aggregates in aqueous media. The size of these aggregates was influenced by concentration, ionic strength, degree of ionization, alkyl substitution and alkyl group length.