betadex and Macular-Degeneration

Drug administration by effective nano-carriers is an emerging and growing technology in the field of bio-medicine and particularly Age -related macular degeneration (AMD). This developed nanomaterials based methods with drug administration maximizes the biocompatibility and systemically increases drug delivery profile for the drugs. Herein, we described the effective drug molecules delivery profiles by the hydrothermally synthesized graphene quantum dots (GQDs) encapsulated with supramolecular β-cyclodextrin (β-CD) as a drug delivery system for AMD. The drug release profiles were analysed and plotted by two different types of drugs ((Bevacizumab (Bev) and Ranibizumab (Ran))) and compounds displayed an initial burst delivery percentage of 55.7 ± 1.6% and 52.2 ± 2.6, respectively, within 15 min. After 1 h, 94.2% (Ran) and 93.1% (Bev) of loaded drug molecules were released from the β-CD encapsulated GQDs in sustained manner. The biocompatibility of the synthesized carriers was investigated quantitatively and qualitatively with the mouse Fibroblast L929 cell line. The biological cell analysis observed by calculated cell count and green fluorescence visualization has been clearly confirmed the samples are non-toxic and highly compatible to the cells with more than 90% cell viability after 5 days cell culture. The observed material properties and biological results demonstrated that the suitability of the developed nano-carriers for the drug delivery system in the AMD.

Topics: Animals; beta-Cyclodextrins; Bevacizumab; Cell Line; Drug Carriers; Fibroblasts; Graphite; Luminescence; Macular Degeneration; Mice; Quantum Dots; Ranibizumab

In the retinal pigment epithelium of patients with age-related macular degeneration (AMD), excess N-retinylidene-N-retinylethanolamine (A2E), a dimer of all-trans-retinal, accumulats to induce inflammatory cytokine secretion and phototoxic effects. Therefore, the reduction of intracellular A2E is a promising approach for the prevention and treatment of AMD. In this study, acid-labile β-cyclodextrin (β-CD)-threaded polyrotaxanes (PRXs) were synthesized and investigated their effects on the removal of A2E accumulated in retinal pigment epithelium cells (ARPE-19) in comparison to nonlabile PRXs and 2-hydroxypropyl β-CD (HP-β-CD) were examined. GC-MS and HPLC studies strongly suggest that the acid-labile PRXs dissociated into their constituent molecules in cells by lysosomal acidification and threaded β-CDs were considered to be released from the PRXs. The released β-CDs formed an inclusion complex with A2E, which promoted the excretion of A2E. Indeed, the acid-labile PRXs effectively reduced intracellular A2E level at approximately a 10-fold lower concentration than HP-β-CD. Accompanied with A2E removal, the toxicity and phototoxicity of A2E were attenuated by treatment with acid-labile PRXs. Because the nonlabile PRX failed to reduce intracellular A2E level and attenuate phototoxicity, intracellular release of threaded β-CDs from the acid-labile PRX might contribute to reducing intracellular A2E. We conclude that acid-labile PRXs are promising candidates for the treatment of macular diseases through the removal of toxic metabolites.

Topics: Acids; beta-Cyclodextrins; Cell Line; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Humans; Hydrogen-Ion Concentration; Macular Degeneration; Photosensitivity Disorders; Retinal Pigment Epithelium; Retinoids; Rotaxanes

The aim of this study was to prepare and characterize the naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles (Nag-CD/CS-NPs) and evaluate their potential for the topical ophthalmic delivery. Naringenin was first complexed with sulfobutylether-β-cyclodextrin (SBE-β-CD), which can significantly enhance the solubility of poorly soluble drugs. Then, nanoparticles were prepared by ionic gelation of chitosan with SBE-β-CD, and their in vitro and vivo properties were investigated, respectively. The resulting nanoparticles showed an average size of 446.4±112.8nm and zeta potential of +22.5±4.91mV with predominant spherical in shape. The FT-IR and DSC confirmed the formation of Nag-CD/CS-NPs. The in vitro release study indicated that Nag-CD/CS-NPs achieved moderate sustained-release effect, and the in vivo study revealed that the prepared nanoparticles was nonirritating to rabbit's eye and had better ability to prolong the residence time than the naringenin suspension, which can significantly increase naringenin bioavailability in the aqueous humor. In conclusion, the developed CD/CS nanoparticles offer a potential alternative for the ocular administration of poorly soluble drugs.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Chitosan; Drug Carriers; Drug Liberation; Female; Flavanones; Macular Degeneration; Male; Nanoparticles; Particle Size; Rabbits; Solubility