Alginate‐Based Microcapsules with a Molecule Recognition Linker and Photosensitizer for the Combined Cancer Treatment

A reactive template method was used to fabricate alginate‐based hydrogel microcapsules. The uniform and well‐dispersed hydrogel capsules have a high drug loading capacity. After they are coated by a folate‐linked lipid mixture on the surface, the capsules possess higher cell uptake efficiency by the molecule recognition between folate and the folate‐receptor overexpressed by the cancer cells. Moreover, in this bioconjugate, the lipid could remarkably reduce the release rate of hydrophilic doxorubicin from the hydrogel microcapsules and encapsulate the hydrophobic photosensitizer hypocrellin B. The biointerfaced capsules could be used as drug carriers for combined treatment against cancer cell proliferation in vitro; this was much more effective than chemotherapy or photodynamic therapy alone.     

Synthesis of Cholesterylated Thiogalactosides for Gene Delivery

A series of cholesterylated thiogalactosides L₁ –L₆ the cell targeting ligands for gene delivery to hepatocytes, was synthesized. Related poly(ethylene glycol) chain was used as a bridge for the attachment of galactoside on one hydroxyl end, while the other hydroxyl end was linked with cholesterol. This design provided an effective entry for the synthesis of a poly(ethylene glycol) compound with the hepatocyte targeting.     

Human Calcitonin Delivered Orally by Means of Nanoparticles Composed of Novel Graft Copolymers

Abstract

The ability of nanoparticles having surface hydrophilic polymeric chains to enhance the oral absorption of human calcitonin was examined in rats. The oral relative bioavailability of calcitonin against its subcutaneous administration was 0.01% without nanoparticles, but increased significantly when it was administered with nanoparticles. Nanoparticles having cationic poly(vinylamine) (PVAm) chains on their surfaces had a relatively stronger enhancing effect than did other nanoparticles. When divinylbenzene was added to the nanoparticle preparation, PVAm nanoparticles with a crosslinked hydrophobic polystyrene core were synthesized. The addition of divinylbenzene resulted in nanoparticles with larger zeta potential through the efficient accumulation of hydrophilic PVAm chains on their surfaces; however, inadequate amounts decreased the zeta potential. Changes in the bioavailability proportional to the zeta potential indicated that the cationic moiety is indispensable for inducing the significant enhancement of calcitonin absorption. The chemical structure of nanoparticles could be optimized by introducing nonionic poly(N‐isopropylacrylamide) (PNIPAAm) or anionic poly(methacrylic acid) chains onto the PVAm nanoparticle surface to effectively further improve the absorption‐enhancing function of PVAm nanoparticles. Finally, the maximum bioavailability of 1.1% was achieved after oral administration of calcitonin with PVAm–PNIPAAm nanoparticles whose components, VAm macromonomer, N‐isopropylacrylamine (NIPAAm) macromonomer, and styrene were copolymerized in the molar ratio of 1.5:0.5:10.     

Atomic Force Microscopy,Transmission Electron Microscopy,and Photon Correlation Spectroscopy: Three Techniques for Rapid Characterization of Optimized Self-Nanoemulsiying Drug Delivery System of Glibenclamide,Carvedilol, and Lovastatin

This article looks at atomic force microscopy as an important aid to characterize the self-nanoemulsifying formulation of glibenclamide, lovastatin, and carvedilol in conjunction with other sophisticated technique, viz., transmission electron microscopy and photon correlation spectroscopy. Sizes obtained by processing the atomic force microscopy (AFM) image are comparable with those obtained from transmission electron microscope. Although in the present study, the mean particle size obtained from photon correlation spectroscopy does not correlate to the findings of atomic force microscopy and transmission electron microscopy, but the poly-disperse index values correlate well with the findings of AFM and transmission electron microscopy where uniform particle size was observed in aqueous dispersion of self-nanoemulsifying formulation of glibenclamide, lovastatin, and carvedilol.     

Structural Transitions of Self-Nanoemulsifying Drug Delivery System of Glibenclamide,Carvedilol, and Lovastatin upon Progressive Aqueous Dilution

The dynamics of morphological transition in amphiphillic systems such as self-nanoemulsifying drug delivery system (SNEDDS) has become an increasingly active field of research in colloidal science. The present contribution deals with the morphological transition of selected optimized SNEDDS formulations of glibenclamide, carvedilol, and lovastatin on progressive aqueous dilution using transmission electron microscopy. The study emphasizes the structural aspects of the systems and stresses the effect of aqueous dilution under which the systems transform from water-in-oil (L₂) phase into bicontinuous structure and, finally, in oil-in-water (L₁) nanodroplets.     

Hydrophobic Derivatives of Dextran Polysaccharide: Characterization and Properties

This study reports the synthesis and characterization of hydrophobic derivatives of dextran in which long alkyl chains substituted a proportion of the hydroxyl groups. These derivatives were characterized by ¹³C and ¹H NMR and infrared spectroscopy. Information about hydrophobic associations in aqueous solutions was obtained by fluorescence spectroscopy in the presence of pyrene and nabumetone probes. These results, in addition to the swelling‐index data of derivatives, showed that there are perspectives of using them as a starting point for models of drug delivery.     

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Two new prodrugs, bearing two and three 5‐fluorouracil (5‐FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5‐FU, they were intended to form complexes through H‐bonds to an organo‐bridged silane prior to hydrolysis‐condensation through sol–gel processes to construct acid‐responsive bridged silsesquioxanes (BS). Whereas 5‐FU itself and the prodrug bearing two 5‐FU units completely leached out from the corresponding materials, the prodrug bearing three 5‐FU units was successfully maintained in the resulting BS. Solid‐state NMR (²⁹Si and ¹³C) spectroscopy show that the organic fragments of the organo‐bridged silane are retained in the hybrid through covalent bonding and the ¹H NMR spectroscopic analysis provides evidence for the hydrogen‐bonding interactions between the prodrug bearing three 5‐FU units and the triazine‐based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and ¹³C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5‐FU thanks to a controlled and targeted drug delivery.     

Fluorescent Protein Capped Mesoporous Nanoparticles for Intracellular Drug Delivery and Imaging

A multifunctional system for intracellular drug delivery and simultaneous fluorescent imaging was constructed by using histidine‐tagged, cyan fluorescent protein (CFP)‐capped magnetic mesoporous silica nanoparticles (MMSNs). This protein‐capped multifunctional nanostructure is highly biocompatible and does not affect cell viability or proliferation. The CFP acts not only as a capping agent, but also as a fluorescent imaging agent. The nanoassembly was activated by histidine‐based replacement, leading to release of drug molecules encapsulated in the nanopores into the bulk solution. The fluorescent imaging functionality would allow noninvasive tracking of the nanoparticles in the body. By combining the drug delivery with cell‐imaging capability, these nanoparticles may provide valuable multifunctional nanoplatforms for biomedical applications.     

Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

We have developed core‐shell‐corona‐type polymeric micelles that can integrate multiple functions in one system, including the capability of accommodating hydrophobic dyes into core and hydrophilic drug into the shell, as well as pH‐triggered drug‐release. The neutral and hydrophilic corona sterically stabilizes the multifunctional polymeric micelles in aqueous solution. The mineralization of calcium phosphate (CaP) on the PAA domain not only enhances the diagnostic efficacy of organic dyes, but also works as a diffusion barrier for the controlled release.