PubMed · 13857601
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[DEXAMETHASONE].. https://pubmed.ncbi.nlm.nih.gov/13857601/
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We previously described the synthesis of starch-based microparticles that were shown to be bioactive (when combined with Bioactive Glass 45S5) and noncytotoxic. To further assess their potential for biomedical applications such as controlled release, three corticosteroids with a similar basic structure-dexamethasone (DEX), 16alpha-methylprednisonole (MP), and 16alpha-methylprednisolone acetate (MPA)-were used as models for the entrapment and release of bioactive agents. DEX, MP, and MPA were entrapped into starch-based microparticles at 10% wt/wt of the starch-based polymer and the loading efficiencies, as well as the release profiles, were evaluated. Differences were found for the loading efficiencies of the three corticosteroids, with DEX and MPA being the most successfully loaded (82 and 84%, respectively), followed by MP (51%). These differences might be explained based on the differential distribution of the molecules within the matrix of the microparticles. Furthermore, a differential burst release was observed in the first 24 h for all corticosteroids with DEX and MP being more pronounced (around 25%), whereas only 12% of MPA was released during the same time period. Whereas the water uptake profile can account for this first stage burst release, the subsequent slower release stage was mainly attributed to degradation of the microparticle network. Differences in the release profiles can be explained based on the structure of the molecule, because MPA, a more bulky and hydrophobic molecule, is released at a slower rate compared with DEX and MP. In this work, it is shown that these carriers were able to sustain a controlled release of the entrapped corticosteroids over 30 days, which confirms the potential of these systems to be used as carriers for the delivery of bioactive agents.
Individual glucocorticoid (GC) sensitivity was determined by measuring the effects of several clinically used GCs on transactivation of the GC-induced leucine zipper (GILZ) gene and on transrepression of the IL-2 gene using quantitative real-time PCR. A clear difference in relative potencies for transactivation and transrepression of the various GCs was observed, suggesting differential effects. To determine whether the in vitro outcomes could predict in vivo effects of GCs, 15 individuals underwent a 0.25-mg dexamethasone (DEX) suppression test (DST) while determining GILZ and IL-2 mRNA levels in their peripheral blood mononuclear cells incubated with hydrocortisone, DEX, budesonide, and prednisolone. No correlations were found between the DST and the two expression assays. However, significant correlations existed between hydrocortisone and DEX (r = 0.52; P = 0.046), hydrocortisone and budesonide (r = 0.48; P = 0.069), and hydrocortisone and prednisolone (r = 0.86; P = 0.007) regarding GILZ mRNA levels, and between hydrocortisone and DEX (r = 0.62; P = 0.014), hydrocortisone and budesonide (r = 0.71; P = 0.003), and hydrocortisone and prednisolone (r = 0.71; P = 0.047) regarding IL-2 mRNA levels. In conclusion, intra- and inter-individual variations in GC sensitivity were observed using two expression assays representing GC-mediated transactivation and transrepression. The two expression assays did not correlate with each other or with the results of the DST. This suggests that regulation of the hypothalamic-pituitary-adrenal axis is more complex. However, within an individual person, these two tests combined might predict what type and dosage of GC will be preferable in individual patients for its inhibitory clinical effects, together with relatively fewer transactivating effects related to adverse effects.
Layer-by-Layer (LbL) stepwise self-assembly of the polyelectrolytes poly(allylamine hydrochloride) and poly(styrenesulfonate) was used to create a macromolecular nanoshell around drug nanoparticles (approximately 150 nm in diameter). Dexamethasone, a steroid often used in conjugation with chemotherapy, was chosen as a model drug and was formulated into nanoparticles using a modified solvent-evaporation emulsification method. Measurement of the zeta potential (zeta-potential) after each polyelectrolyte layer was electrostatically added confirmed the successful addition of each layer. Additionally, data acquired from X-ray photon spectroscopy (XPS) indicated the presence of peaks representative of each physisorbed polyelectrolyte layer. Surface modification of the nanoshell was performed by covalently attaching poly(ethylene glycol) (PEG) with a molecular weight of 2000 to the outer surface of the nanoshell. Zeta potential measurements and XPS indicated the presence of PEG chains at the surface of the nanoshell. The polymeric nanoshell on the surface of the drug nanoparticle provides a template upon which surface modifications can be made to create a stealth or targeted drug delivery system.