New environmental sensitive system for colon-specific delivery of peptidic drugs.
Nano and micro preparative technologies for the realization of pharmaceutical carriers represent an actual strategy for reaching the therapeutic success of drugs, particularly in the case of peptidic drugs. Vancomycin is here entrapped in carriers composed by a swellable, mucoadhesive and biodegradable albumin core, coated with fatty acids able to improve a colon-specific release. Bovine serum albumin nanospheres (core) were prepared from protein solutions using a coacervation method followed by thermal cross-linking at different temperature, or from protein solutions at different pHs using a coacervation method followed by thermal cross-linking at 75 degrees C. Solid nanospheres were collected by freeze-drying, loaded by soaking from solutions of vancomycin and subsequently coated with myristic, palmitic or stearic acid by spray-drying technique obtaining microcapsules. Nanosphere dimensions and polydispersity, drug loading capacity, swelling ability and mucoadhesion properties were evaluated, as well as in vitro release behaviour. The results indicated that nanospheres present an adequate loading capacity, a great swelling tendency and good mucoadhesion ability. Moreover, albumin cores showed a pH-dependent release according to the structure of thermally denaturated protein in different experimental conditions, while microcapsules showed a pH-dependent release according to the different fatty acids solubility in acidic and alkaline media.
Luppi
Barbara
B
Department of Pharmaceutical Sciences, University of Bologna, Via S. Donato 19/2, Bologna, Italy. barbara.luppi@unibo.it
Bigucci
Federica
F
Cerchiara
Teresa
T
Mandrioli
Roberto
R
Di Pietra
Anna Maria
AM
Zecchi
Vittorio
V
D000418:Albumins / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D004777:Environment; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D008027:Light; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage*; D011489:Protein Denaturation; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry; D014961:X-Ray Diffraction
D000418:Albumins; D000900:Anti-Bacterial Agents; D002214:Capsules; D003432:Cross-Linking Reagents; D010455:Peptides; D014640:Vancomycin