Maria D. Moya-Ortega

Cyclodextrin-based nanogels for pharmaceutical and biomedical applications

Hydrophilic nanogels combine the advantages of hydrogels with certain advantages that are inherent in their nanoscale size. Similar to macrogels, nanogels can contain and protect drugs and regulate their release by incorporating high-affinity functional groups, stimuli-responsive conformations and biodegradable bonds into the polymer network. Similar to nanoparticles, nanogels can easily be administered in liquid form for parenteral drug delivery. The nanoscale size of nanogels gives them a high specific surface area that is available for further bioconjugation of active targeting agents. Biodistribution and drug release can be modulated through size adjustments. The incorporation of hydrophilic cyclodextrin (CD) moieties into the polymeric network of the nanogels provides them with a drug loading and release mechanism that is based on the formation of inclusion complexes without decreasing the hydrophilicity of the network. The covalent attachment of CD molecules to the chemically crosslinked networks may enable the CDs to display fully their ability to form complexes, while simultaneously preventing drug release upon media dilution. The preparation, characterization and advantages for pharmaceutical and biomedical applications of CD-based nanogels are reviewed in this article.

Dexamethasone eye drops containing γ-cyclodextrin-based nanogels.

Sustained release aqueous eye drops of dexamethasone, based on cyclodextrin (CD) nanogels, were designed and tested in vivo. γCD units were cross-linked in the form of nanogels by means of an emulsification/solvent evaporation process. The composition of the nanogels was optimized with regard to drug loading and release rate. The eye drops consisted of an aqueous solution of dexamethasone in 2-hydroxypropyl-γ-cyclodextrin (HPγCD) medium containing γCD nanogels. The nanogel eye drops (containing 25 mg dexamethasone per ml) were tested in rabbits and compared to the commercially available product Maxidex(®) (suspension with 1 mg dexamethasone per ml). One drop administration of the nanogel eye drops resulted in nearly constant dexamethasone concentration for at least 6h in the tear fluid (mean concentration±SD=295±59 μg/ml) whereas the concentration after administration of Maxidex(®) fell rapidly from 9.72±3.45 μg/ml 1 h after application to 3.76±3.26 μg/ml 3 h after application. The maximum dexamethasone concentration in the aqueous humor (2 h after application) was 136±24 mg/ml after application of the nanogel eye drops, and only 44.4±7.8 μg/ml after application of Maxidex(®). The dexamethasone nanogel eye drops were well tolerated with no macroscopic signs of irritation, redness or other toxic effects.

Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

The objective of the present study was to shed some light on pharmacokinetics of cyclodextrins (CDs) and drugs after oral and parenteral administration of inclusion complexes.

Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid.

We have developed nanoparticle γ‐cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.

Dorzolamide cyclodextrin nanoparticle suspension eye drops and trusopt in rabbit

PURPOSEnDorzolamide nanoparticle γ-cyclodextrin eye drops may prolong the effect of dorzolamide on intraocular pressure. We test whether the nanoparticle drops have an irritating or toxic effect on the eye in an in vivo rabbit model.nnnMETHODSnEighteen pigmented rabbits were divided into 4 groups receiving dorzolamide nanoparticle γ-cyclodextrin eye drops×1/day or×2/day, Trusopt® (dorzolamide HCl)×3/day, and untreated controls that received no drops. The rabbits received treatment for 1 month. After sacrifice, 33 eyes and 25 Harderian glands were evaluated for histopathology in a masked way.nnnRESULTSnMild inflammation was seen in 19/31 eyes and 13/23 Harderian glands. The difference in inflammation (n=eyes/n=glands)between the γ-cyclodextrin nanoparticle eye drops×1/day (n=5/5),×2/day (n=5/3), Trusopt (n=7/4), or untreated control (n=2/0) groups was nonsignificant in both eyes and glands (P=0.87 and P=0.92) Acute inflammation was seen in 1 Harderian gland that received γ-cyclodextrin nanoparticle eye drops×2/day. The difference in conjunctival injection between the groups was nonsignificant (P=0.30).nnnCONCLUSIONSnDorzolamide γ-cyclodextrin nanoparticle eye drops are no more locally toxic or irritating to the eye than Trusopt.