132877-29-3Relevant academic research and scientific papers
Supramolecular diversity through click chemistry: Switching from nanomicelles to 1D-nanotubes and tridimensional hydrogels
Assali, Mohyeddin,Cid, Juan-Jose,Fernandez, Inmaculada,Khiar, Noureddine
, p. 4250 - 4261 (2013)
The size and shape of nanoparticles are of prominent importance for their biological activities and for their application as smart drug delivery systems. Thus, synthetic designs allowing divergent synthesis of nanoscale materials with controlled size, morphology, and surface chemistry are currently highly desirable, but they remain a major challenge. Herein, we report a simple method for the creation of supramolecular diversity from structurally related diacetylenic-based glycolipids. We have found that neoglycolipids with an amide function between the hydrophilic and hydrophobic part of the amphiphile afford tridimensional micelles, while those having a triazole self-organize into 1D-nanotubes. Additionally, at higher concentrations, the clicked amphiphiles form hydrogels through three-dimensional networks of bundled nanotubes. Photopolymerization of the obtained nanomaterials leads to the formation of conjugated polydiacetylene backbone of alternating enyne groups, which rigidify glyconanomaterial structures enhancing their physical stability. The obtained nanostructures were extensively characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) techniques, enabling the confirmation of the formation of tubular structures in water for all triazolo-substituted neoglycolipids and micellar structures for the glycolipid containing an amide group. This fact refutes the so-called isosteric character of 1,2,3-triazole and amide groups, at least, at the supramolecular level and point out to the possibility of using the CuAAC between azides and alkynes to create supramolecular diversity at the nanoscale. The functionality of the gel was, moreover, evaluated as a nanocontainer for the incarceration and controlled release of the antitumoral topotecan.
The acidic microclimate in poly(lactide-co-glycolide) microspheres stabilizes camptothecins
Shenderova, Anna,Burke, Thomas G.,Schwendeman, Steven P.
, p. 241 - 248 (2007/10/03)
Purpose. The camptothecin (CPT) analogue, 10-hydroxycamptothecin (10- HCPT) has been shown previously to remain in its acid-stable (and active) lactone form when encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres (1). The purpose of this study was to determine the principal mechanism(s) of 10-HCPT stabilization. Methods. CPTs were encapsulated in PLGA 50:50 microspheres by standard solvent evaporation techniques. Microspheres were eroded in pH 7.4 buffer at 37°C. The ratio of encapsulated lactone to carboxylate was determined by HPLC as a function of time, initial form of drug encapsulated, fraction of co-encapsulated Mg(OH)2, CPT lipophilicity, and drug loading. Two techniques were developed to assess the microclimate pH, including: i) measurement of H+ content of the dissolved microspheres in an 80:20 acetonitrile/H2O mixture and ii) confocal microscopy of an encapsulated pH-sensitive dye, fluorescein. Results. The encapsulated carboxylate converted rapidly to the lactone after exposure to the release media, indicating the lactone is favored at equilibrium in the microspheres. Upon co-encapsulation of Mg(OH)2, the trend was reversed, i.e., the lactone rapidly converted to the carboxylate form. Measurement of - log(hydronium ion activity) (pa(H)/*) of dissolved microspheres with pH- electrode and pH mapping with fluorescein revealed the presence of an acidic microclimate. From the measurements of H+ and water contents of particles hydrated for 3 days, a microclimate pH was estimated to be in the neighborhood of 1.8. The co-encapsulation of Mg(OH)2 could both increase the pa(H)/* reading and neutralize pH in various regions of the microsphere interior. Varying the drug lipophilicity and loading revealed that the precipitation of the lactone could also stabilize CPT. Conclusions. PLGA microspheres prepared by the standard solvent evaporation techniques develop an acidic microclimate that stabilizes the lactone form of CPTs. This microclimate may be neutralized by co-encapsulating a base such as Mg(OH)2, as suggested by previous work with poly(ortho esters) (2).
