Abstract
Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer's disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300 nm and 0.33 nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour.
| Original language | English |
|---|---|
| Pages (from-to) | 559-565 |
| Number of pages | 7 |
| Journal | European Journal of Pharmaceutical Sciences |
| Volume | 44 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 20 2011 |
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Keywords
- Albumin nanospheres
- Beta cyclodextrin
- Hydroxypropyl beta cyclodextrin
- Nasal administration
- Sulphobutylether beta cyclodextrin
- Tacrine hydrochloride
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine. / Luppi, Barbara; Bigucci, Federica; Corace, Giuseppe; Delucca, Alice; Cerchiara, Teresa; Sorrenti, Milena; Catenacci, Laura; Di Pietra, Anna Maria; Zecchi, Vittorio.
In: European Journal of Pharmaceutical Sciences, Vol. 44, No. 4, 20.11.2011, p. 559-565.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine
AU - Luppi, Barbara
AU - Bigucci, Federica
AU - Corace, Giuseppe
AU - Delucca, Alice
AU - Cerchiara, Teresa
AU - Sorrenti, Milena
AU - Catenacci, Laura
AU - Di Pietra, Anna Maria
AU - Zecchi, Vittorio
PY - 2011/11/20
Y1 - 2011/11/20
N2 - Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer's disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300 nm and 0.33 nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour.
AB - Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer's disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300 nm and 0.33 nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour.
KW - Albumin nanospheres
KW - Beta cyclodextrin
KW - Hydroxypropyl beta cyclodextrin
KW - Nasal administration
KW - Sulphobutylether beta cyclodextrin
KW - Tacrine hydrochloride
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UR - http://www.scopus.com/inward/citedby.url?scp=80455134830&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2011.10.002
DO - 10.1016/j.ejps.2011.10.002
M3 - Article
VL - 44
SP - 559
EP - 565
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
IS - 4
ER -