The exfoliation effects of MMC, doxorubicin and gemcitabine allow for good tissue penetration of these drugs with no additional effect from CNP treatment of bladders. The observed exfoliation effect of these amine-containing drugs probably arises from a cationic interaction with the mucus and urothelium cell layer in a manner similar to that previously reported for CNPs. These studies suggest that the lack of long-term clinical efficacy of these drugs may not arise from poor intravesical drug penetration but may result from a rapid diffusion of the drugs into the deeper vascularised muscular region with rapid drug clearance. The enhanced uptake of PTX or DTX following co-administration with MMC, doxorubicin or gemcitabine probably arises from the removal of the urothelial barrier by exfoliation allowing for improved taxane partitioning into superficial layers. These effects may allow for dual drug intravesical strategies offering greatly improved taxane uptake and potential additive drug effects for improved efficacy.

The use of cationic polyglycerols with higher levels of amine termination allows for an enhanced uptake of DTX into bladder tissues as compared to commercial (Taxotere) formulations. These increased drug levels probably arise from exfoliation processes resulting in a temporary elimination of the urothelial permeability barrier and increased drug penetration into the tissue.

Epigallocatechin gallate (EGCG) and tannic acid (TA) are known to increase the aqueous solubility and cellular uptake of the hydrophobic drugs docetaxel, paclitaxel, amphotericin B, and curcumin. In this study the practical application of gallate-based solubilization phenomena for the uptake of these drugs into dermal and bladder tissue and of lidocaine for wound healing application was studied. The penetration of all these drugs into pig skin or docetaxel into pig bladder using EGCG or TA formulations was measured. Overall, EGCG and TA particulate or propylene glycol paste formulations of drugs allowed for greatly increased levels of drug uptake into skin as compared to control formulations. EGCG/propylene glycol pastes allowed for rapid lidocaine uptake into skin. EGCG and TA formulations of docetaxel allowed for approximately 10 fold increases in bladder tissue uptake of docetaxel over tween based solutions. Morphologically, both EGCG and TA caused a mild, dose dependent exfoliation of the bladder wall. Both EGCG and TA formed injectable viscous pastes with propylene glycol which solidified in water and degraded and released lidocaine over 2e35 days. These data support the use of EGCG and TA based formulations of certain drugs for improved dermal, bladder and wound applications.

No abstract