Polypseudorotaxanes of Pegylated α-Cyclodextrin/Polyamidoamine Dendrimer Conjugate with Cyclodextrins as a Sustained Release System for DNA

Nonviral gene delivery suffers from a number of limitations including short transgene expression times and low transfection efficiency. In this study, we examined whether polypseudorotaxanes (PPRXs) of polyethylene glycol (PEG, molecular weight: 2,000)-grafted α-cyclodextrin (α-CyD)/ polyamidoamine dendrimer conjugate (PEG-α-CDE) with CyDs have the potential for the novel sustained release systems for plasmid DNA (pDNA). The PEG-α-CDE/pDNA complex formed PPRXs with α-CyD and γ-CyD solutions, but not with β-CyD solution. In the PEG-α-CDE/CyDs PPRX systems, 20.6 mol of α-CyD and 11.8 mol of γ-CyD were involved in the PPRXs formation with one PEG chain by α-CyD and γ-CyD, respectively, consistent with in the PEG-dendrimer/CyDs systems. PEG-α-CDE/pDNA/α-CyD PPRX and PEG-α-CDE/pDNA/γ-CyD PPRX formed hexagonal and tetragonal columnar channels in the crystalline phase, respectively. In addition, the CyDs PPRX provided the sustained release of pDNA from PEG-α-CDE complex with pDNA at least 72 h in vitro. The release of pDNA from CyDs PPRX retarded as the volume of dissolution medium decreased. Furthermore, the PEG-α-CDE/γ-CyD PPRX system showed sustained transfection efficiency after intramuscular injection to mice at least for 14 days. These results suggest that the PEG-α-CDE/CyD PPRX systems are useful for novel sustained DNA release systems

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products

Relationship between Bone Mineral Density and Body Composition Estimated by Dual-Energy X-ray Absorptiometry : Comparison between Groups Aged 20-39 and 40-59 Years

Bone mineral density (BMD) is affected by lean body mass and body weight to various degrees in the course of aging. The attempt of this study is to determine the optimal time to begin prevention of osteoporosis. In this study, female hospital employees aged 20-59 years were divided into 2 age groups, 20-39 years and 40-59 years based on age at peak BMD, and the relations of total BMD, subtotal BMD and lumbar spine BMD to lean body mass and body weight were examined in both groups. Subtotal BMD was calculated by subtracting head BMD from total BMD along with whole body measurement. While persistent positive correlations were found among all factors in the 20-39-year-old group, subtotal BMD and lumbar spine BMD were positively correlated to lean body mass in the 40-59-year-old group. Thus, lean body mass and body weight appeared to exert a profound influence on subtotal BMD in those aged 20-39 years, but lean body mass in those aged 40-59 years. Lean body mass appears to provide the best prediction of subsequent development of osteoporosis