MARC 主機 00000nam  2200361   4500 
001    AAI3170725 
005    20061103104853.5 
008    061103s2005                        eng d 
020    9780542068737 
035    (UnM)AAI3170725 
040    UnM|cUnM 
100 1  Devarakonda, Bharathi 
245 10 Poly(amidoamine) (PAMAM) dendrimers as solubility and 
       permeation enhancers 
300    220 p 
500    Source: Dissertation Abstracts International, Volume: 66-
       04, Section: B, page: 2079 
500    Major Professor:  Melgardt M. de Villiers 
502    Thesis (Ph.D.)--University of Louisiana at Monroe, 2005 
520    The aim of this study was to synthesize and investigate 
       the solubilization and permeation enhancing potential of 
       PAMAM dendrimers with different generation sizes and 
       functional groups. Dendrimers are highly branched and 
       reactive three-dimensional macromolecules with all bonds 
       emanating from a central core. Since their introduction in
       the mid 1980's, this novel class of polymeric materials 
       has attracted considerable attention because of their 
       unique structures and properties. Compared with 
       traditional linear polymers, dendrimers have more 
       accurately controlled structures, with a globular shape, a
       single molecular weight, and a large number of 
       controllable peripheral surface functionalities 
520    Many families of dendrimers with various core molecules 
       and building monomers have been synthesized and are 
       commercially available now. But, the family of dendrimers 
       most investigated for drug delivery is the PAMAM 
       dendrimers. PAMAM dendrimers are biocompatible, non-
       immunogenic, water-soluble and possess terminal-modifiable
       amine functional groups for binding various targeting or 
       guest molecules. The internal cavities of PAMAM dendrimers
       can host metals or guest molecules because of the unique 
       functional architecture, which contains tertiary amines 
       and amide linkages 
520    In the present study, the solubilization potential of 
       PAMAM dendrimers was investigated using four practically 
       water insoluble drugs (niclosamide, nifedipine, furosemide,
       and paclitaxel) as model drugs. Further, the 
       solubilization potential of the dendrimers was compared 
       with that of traditionally used supramolecular compounds, 
       i.e. cyclodextrins. The permeation enhancement potential 
       of the dendrimers was investigated after oral and topical 
       administration of drug-dendrimer complexes, and on the 
       permeability of paclitaxel across cancerous cells 
520    Results showed that PAMAM dendrimers have the potential to
       significantly increase the aqueous solubility of these 
       model drugs. In addition, significantly higher solubility 
       of the drugs was observed in the presence of the 
       dendrimers than in the presence of cyclodextrins. Also in 
       vitro permeation studies using dendrimers as permeation/
       penetration enhancers showed that PAMAM dendrimers have 
       the potential to significantly increase the permeability 
       of drugs for oral and topical delivery and cellular entry 
       of drugs across cancerous cells. Significant differences 
       in the solubilization and permeation enhancement 
       properties were observed between the PAMAM dendrimers with
       different generation sizes and surface functional groups 
       (amine terminated versus ester terminated dendrimers) 
590    School code: 1352 
590    DDC 
650  4 Chemistry, Pharmaceutical 
650  4 Health Sciences, Pharmacy 
690    0491 
690    0572 
710 20 University of Louisiana at Monroe 
773 0  |tDissertation Abstracts International|g66-04B 
856 40 |u