TY - JOUR
T1 - Modified doxorubicin for improved encapsulation in PVA polymeric micelles
AU - Orienti, Isabella
AU - Zuccari, G.
AU - Fini, A.
AU - Rabasco, A. M.
AU - Carosio, R.
AU - Raffaghello, L.
AU - Montaldo, P. G.
PY - 2005/1
Y1 - 2005/1
N2 - Polyvinylalcohol, partially substituted with lipophilic acyl chains, generates polymeric micelles in aqueous phase, containing a hydrophobic core able to encapsulate lipophilic drugs. Two types of polymers were obtained by conjugation of polyvinylakohol with oleoyl or linoleoyl chains as pendant groups. The polymers, at a substitution degree of ∼1%, are soluble in water and form polymeric micelles whose size increases with polymer concentration. Doxorubicin was hydrophobized, by linking an oleoyl chain via amide bond, to make the drug more similar to the substituted polymers and promote its encapsulation into the inner core of the micelles. The properties of the drug-polymer systems were evaluated in solution by dynamic light scattering technique and correlated to the physicochemical characteristics of the drug and the substituted polymers. Solubilization tests revealed that the similarity of the chain, in both the polymer and the drug, promotes better drug encapsulation in the oleoyl than linoleoyl derivative. The drug-polymer systems are stable in phosphate buffer saline (pH 7.4) at 37°C, and the release of the drug is activated by the presence of the proteolytic enzyme pronase-E. The enzyme activated drug release and the size of the polymeric micelles, compatible with the pore dimensions of the tumor vessels, make these systems interesting for targeting lipophilic drugs to solid tumors, where the proteolytic enzyme concentration strongly raises with respect to the other body compartments.
AB - Polyvinylalcohol, partially substituted with lipophilic acyl chains, generates polymeric micelles in aqueous phase, containing a hydrophobic core able to encapsulate lipophilic drugs. Two types of polymers were obtained by conjugation of polyvinylakohol with oleoyl or linoleoyl chains as pendant groups. The polymers, at a substitution degree of ∼1%, are soluble in water and form polymeric micelles whose size increases with polymer concentration. Doxorubicin was hydrophobized, by linking an oleoyl chain via amide bond, to make the drug more similar to the substituted polymers and promote its encapsulation into the inner core of the micelles. The properties of the drug-polymer systems were evaluated in solution by dynamic light scattering technique and correlated to the physicochemical characteristics of the drug and the substituted polymers. Solubilization tests revealed that the similarity of the chain, in both the polymer and the drug, promotes better drug encapsulation in the oleoyl than linoleoyl derivative. The drug-polymer systems are stable in phosphate buffer saline (pH 7.4) at 37°C, and the release of the drug is activated by the presence of the proteolytic enzyme pronase-E. The enzyme activated drug release and the size of the polymeric micelles, compatible with the pore dimensions of the tumor vessels, make these systems interesting for targeting lipophilic drugs to solid tumors, where the proteolytic enzyme concentration strongly raises with respect to the other body compartments.
KW - Doxorubicin-Oleate
KW - Drug Encapsulation
KW - Dynamic Light Scattering
KW - Polymeric Micelles
KW - Polyvinylalcohol-Co-Vinyloleate and Co-Vinyllinoleate
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U2 - 10.1080/10717540590889574
DO - 10.1080/10717540590889574
M3 - Article
C2 - 15801716
AN - SCOPUS:11244299449
VL - 12
SP - 15
EP - 20
JO - Drug Delivery
JF - Drug Delivery
SN - 1071-7544
IS - 1
ER -