betadex and caprolactone

A pillar[5]arene-based nonionic polyrotaxane (PR) with star-poly(ε-caprolactone) ( S-PCL) as the axle, pillar[5]arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with β-cyclodextrin end-capped pH-stimulated poly(acrylic acid) (CD-PAA) via a host-guest interaction to form the supramolecular pseudoblock polymer PR-PAA. This supramolecular pseudoblock polymer could self-assemble in aqueous solution to produce PR-PAA-based supramolecular vesicular nanoparticles (PR-SVNPs), which present significantly enhanced drug loading capacity (DLC, 45.6%) of DOX, much higher than those of superamphiphiles (PCL-PAA, 17.1%). Such a high DLC of PR-SVNPs can be most probably attributed to the greatly decreased crystallinity of PCL in PR. Moreover, the loaded drugs could be selectively released in an acidic microenvironment-responsive manner. Compared to free DOX, the DOX-loaded PR-SVNPs (DOX@PR-SVNPs) shows much enhanced cellular uptake and cytotoxicity against the SMMC-7721. More importantly, thanks to the enhanced permeability and retention (EPR) effect, DOX@PR-SVNPs exhibits appealing features such as extremely low toxicity, highly efficient intratumoral accumulation and substantial antitumor efficacy in vivo.

Topics: Acrylic Resins; Adamantane; Animals; Antineoplastic Agents; beta-Cyclodextrins; Caproates; Cell Line, Tumor; Doxorubicin; Lactones; Mice; Mice, Inbred BALB C; Nanoconjugates; Rotaxanes; Surface-Active Agents

In the last decades, nano-oncologicals bearing a polyethylene glycol (PEG) coating are being emerging as biomimetic devices able to drive their drug cargo to solid tumors through passive mechanisms. To improve selectivity toward cancer cells, nanocarriers decorated with the small ligand folate have been widely investigated. Nevertheless, a great challenge remains the effective exposition of folate on nanoparticles (NPs), which is a key prerequisite to ensure the correct binding to receptor and the following endocytic uptake. On these premises, in this study we propose a novel strategy to produce core-shell folate-targeted NPs based on diblock copolymers of poly(ε-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-β-cyclodextrin (HPβCD). PCL4300-PEG2000 and PCL4300-PEG2000-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HPβCD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HPβCD demonstrated a highly extended conformation of PEG chains in the shell, an enhanced interaction with a specific antibody against folate and a higher uptake in cells overexpressing folate receptor. Overall, these results suggest that proper manipulation of PEG shell conformation through HPβCD can represent a novel non-covalent strategy to modify shell features.

Topics: A549 Cells; beta-Cyclodextrins; Calorimetry; Caproates; Cell Line, Tumor; Drug Carriers; Endocytosis; Folate Receptors, GPI-Anchored; Folic Acid; Humans; Lactones; Nanoparticles; Particle Size; Polyesters; Polyethylene Glycols; Proton Magnetic Resonance Spectroscopy

A novel amphiphilic star-shaped inorganic-organic hybrid copolymer polyhedral oligomeric silsesquioxane-poly(ɛ-caprolactone)-β-cyclodextrin (POSS-PCL-β-CD) was synthesized by ring-opening polymerization (ROP) and click chemistry. The amphiphilic copolymer can self-assemble into hybrid micelles with hydrophobic POSS-PCL chain encapsulating Fe3O4 nanoparticles as the core and β-CD as the shell after mixing with Fe3O4 nanoparticles in solvent and dialysis against water. The chemical structure of POSS-PCL-β-CD was characterized by (1)H NMR and the morphology of the magnetic hybrid micelles was characterized by TEM and DLS. Due to the host-guest interaction of β-CD with bisphenol A (BPA), POSS-PCL-β-CD/Fe3O4 hybrid micelles present good adsorption capacity in removal of BPA from aqueous solution. Magnetic measurement reveals that POSS-PCL-β-CD/Fe3O4 hybrid micelles still exhibit magnetism for separation by an external magnetic field, indicating that these magnetic hybrid micelles may have potential application in the field of environmental protection.

Topics: Benzhydryl Compounds; beta-Cyclodextrins; Caproates; Ferric Compounds; Lactones; Magnetic Phenomena; Metal Nanoparticles; Micelles; Phenols; Polyesters; Water

The synthesis of cyclodextrin-centred star polymers via thiol-ene addition of per-6-thio-β-cyclodextrin (CD-(SH)(7)) with vinyl terminated polymers is described. The obtained thiol-ene product was employed as an initiator for ring opening polymerization (ROP) of ε-caprolactone (ε-CL).

Topics: beta-Cyclodextrins; Caproates; Cellulose; Cyclodextrins; Lactones; Polymerization; Sulfhydryl Compounds

The encapsulation of a Brucella ovis extract (HS) in microparticles has been proved effective against experimental infections in mice. This work describes different strategies to increase the HS loading and prepare large batches as necessary to test this vaccine in ovine. The mixture of HS with beta-cyclodextrin was optimized in order to increase the HS loading in microparticles. On the other hand, TROMS ('Total Recirculation One-Machine System') led microparticles with a more homogeneous size than the laboratory or standard procedure. Moreover, the initial burst release of HS from the standard microparticles was higher than for the TROMS ones. In fact, standard microparticles displayed a higher amount of adsorbed HS. On the contrary, both preparative methods were found effective to preserve the integrity and anti-genicity of the loaded HS. In summary, beta-CD can be used to increase the loading of large hydrophobic materials and TROMS is a valid large production of antigen-loaded microparticles.

Topics: Antigens, Bacterial; Bacterial Outer Membrane Proteins; beta-Cyclodextrins; Brucella ovis; Brucella Vaccine; Brucellosis; Caproates; Chemical Phenomena; Chemistry, Physical; Drug Delivery Systems; Lactones; Microspheres; Particle Size; Technology, Pharmaceutical