Pharmacokinetic Properties and Applications as Drug Carriers

As far as dendrimers' pharmacokinetics are concerned, the biodistribution of [14C] labeled PAMAM dendrimers after intravenous injection was determined for generation 3, 5, and 7 PAMAM dendrimers.42 At each generation, the biodistribution characteristics were different. Generation 3 dendrimers showed the highest accumulation in kidney (15% of dose/g tissue over 48 h); however, generation 5 and 7 dendrimers preferentially accumulated in the pancreas (peak level 32% dose/g tissue at 24 h and 20% of dose/g tissue at 2 h, respectively). In addition, generation 7 dendrimers showed extremely high urinary excretion with values of 46 and 74% of dose/g tissue at 2 and 4 h, respectively. These results suggested that the biodistribution of a dendrimer depended on the generation because physicochemical properties were determined by the generation. Other reports described the biodistribution of [3H]-labeled neutral and positively charged generation 5 PAMAM dendrimers in a tumor-bearing mouse model.43 Both neutral and positively charged dendrimers showed a similar biodistribution trend 1 h after intravenous injection; the highest level was found in the lungs, kidney, and liver (positive, 28-6.1% of dose/g tissue; neutral, 5.3-2.9% of dose/g tissue) followed by the tumor, spleen, and pancreas (positive, 3.3-2.6% of dose/g, tissue; neutral 3.4-0.92% of dose/g tissue). Differences between neutral and positively charged dendrimers were observed for accumulation in the lung. A high lung accumulation of cationic dendrimer was found compared with conventional cationic liposomes, and this may be explained by the stacking to the capillary vessels of the lung. Moreover, [14C]-labeling of the dendrimer results in partial neutralization of the dendrimer. Therefore, different biodistribution properties were observed in the lung and liver accumulation between [14C]-and [3H]-labeled dendrimers. These results suggest that the biodistribution properties of radio-labeled dendrimers have to be examined carefully, taking into consideration the surface charge caused by the radio-labeling. As far as tumor accumulation is concerned, this may be explained by the EPR effect.

Drug delivery applications of dendrimers have been studied by Szoka and co-workers.44 The biodistribution of doxorubicin covalently bound via a hydrazone linkage with a polyester dendritic scaffold based on 2,2-bis(hydroxymethyl)propanoic acid was examined. After intravenous injection, doxorubicin was extracted from the tumor and organs. Compared with free doxorubicin, the serum half-life was significantly increased. Therefore, this dendrimer would be a promising drug carrier for cancer therapy.

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment