title: Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery.
abstract: Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1-4) on the base of their anti-neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and ζ-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions, and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena S.r.l., via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Vignaroli
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Calandro
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena S.r.l., via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena S.r.l., via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Coniglio
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena S.r.l., via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Iovenitti
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Tavanti
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica and Istituto Toscano Tumori, Core Research Laboratory, Via Fiorentina 1, 53100, Siena, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Colecchia
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Dreassi
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Valoti
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Benedetto VX 3, 16132, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica and Istituto Toscano Tumori, Core Research Laboratory, Via Fiorentina 1, 53100, Siena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiariello
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena S.r.l., via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Siena, Italy.|Biotechnology College of Science and Technology, Temple University, Biolife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D008081:Liposomes; D011720:Pyrazoles; D011743:Pyrimidines; C000606692:pyrazolylpyrimidine