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5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47 +/- 11 and 67 +/- 12 microg 5-FU mg(-1) microspheres and the percentage of entrapment efficiency was between 52 +/- 12 and 74 +/- 13. Microspheres were of small size (average diameter: 0.9 +/- 0.4-1.4 +/- 0.8 microm microspheres without drug; 1.1 +/- 0.5-1.7 +/- 0.9 microm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger Tg. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of Tg of the polymer of the microspheres. The presence of 5-FU did not modify the Tg values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28-129 h) was in the order PLA > PLGA 75/25 > PLGA 50/50. A burst effect (17-20%) was observed during the first hour and then a period of constant release rate (3.52 +/- 0.82-1.46 +/- 0.26 microg 5-FU h(-1) per milligram of microspheres) up to 8 or 13 h, depending on the polymer, was obtained.

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BACKGROUND: Poly(N‐isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by inverse microemulsion to be used for the controlled release of anti‐tumour drugs. Different methods were used to obtain drug‐loaded xerogels, and their effect on drug release was studied, and evaluated using mathematical modelling. RESULTS: Nanoparticulate hydrogels, with a z‐average diameter of 170 nm, were loaded with 5‐fluorouracil (5‐FU), methotrexate (MTX) or mitomycin C (MMC) by using spray drying (SD) and freeze drying (FD). Xerogels obtained by SD consisted of individual and independent particles, whereas particles established interactions in xerogels obtained by FD. Total drug release took place at 6 and 7 h from 5‐FU‐loaded and MMC‐loaded xerogels prepared by SD, whereas MTX was expelled from the xerogels formed using the SD process. Drug release was slower from xerogels prepared by FD: 5‐FU at 32 h, MMC at 120 h and MTX at 240 h. The Higuchi model most aptly fits the dissolution data. Non‐Fickian and Fickian release behaviour can be attributed to SD and FD formulations, respectively. CONCLUSION: The amount of drug loaded, the morphology of xerogels as well as the drug release characteristics not only depend on the drug but also mainly on the process used to obtain the drug‐loaded PNIPA xerogels. Copyright © 2008 Society of Chemical Industry

Folate-targeted poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] nanohydrogel (F-SubMG) was loaded with 5-fluorouracil (5-FU) to obtain low (16.3 ± 1.9 μg 5-FU/mg F-SubMG) and high (46.8 ± 3.8 μg 5-FU/mg F-SubMG) load 5-FU-loaded F-SubMGs. The complete in vitro drug release took place in 8 h. The cytotoxicity of unloaded F-SubMGs in MCF7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 μM 5-FU by 5-FU-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was higher in HeLa cells because they are folate receptor positive. After subcutaneous administration (28 mg 5-FU/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin. Histological studies indicated that the OPEN ACCESSPolymers 2011, 3 1108 F-SubMGs were surrounded by connective tissue, without any signs of rejections, even 60 days after injection. Pharmacokinetic study showed an increase in MRT (mean residence time) of 5-FU when the drug was administered by drug-loaded F-SubMGs.

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