Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs.Delivery of drugs through the skin has been an attractive as well as a challenging area for research. Advances in modern technologies are resulting in a larger number of drugs being delivered transdermally including conventional hydrophobic small molecule drugs, hydrophilic drugs and macromolecules. Transdermal systems are a desirable form of drug delivery because of the obvious advantages over other routes of delivery. Transdermal delivery provides convenient and pain-free self-administration for patients. It eliminates frequent dosing administration and plasma level peaks and valleys associated with oral dosing and injections to maintain a constant drug concentration, and a drug with a short halflife can be delivered easily. All this leads to enhanced patient compliance, especially when long-term treatment is required, as in chronic pain treatment and smoking cessation therapy. Avoidance of hepatic first-pass metabolism and the GI tract for poorly bioavailable drugs is another advantage of transdermal delivery. Elimination of this first-pass effect allows the amount of drug administered to be lower, and hence safer in hepato-compromised patients, resulting in the reduction of adverse effects. Transdermal systems are generally inexpensive when compared with other therapies on a monthly cost basis, as patches are designed to deliver drugs from 1 to 7 days. The other advantage of transdermal delivery is that multiple dosing, on-demand or variable-rate delivery of drugs, is possible with the latest programmable systems, adding more benefits to the conventional patch dosage forms. The general acceptability of transdermal products by patients is very high, which is also evident from the increasing market for transdermal products. The transdermal drug delivery market, worth $12.7 billion dollars in 2005, is expected to reach $32 billion in 2015 [1].
The objectives of these studies were to investigate and compare solid lipid nanoparticles (SLNs) of two anthracyclines, idarubicin (IDA) and doxorubicin (DOX), against Pgp-mediated multiple drug resistance (MDR.) in-vitro and in-vivo using different human and murine cancer cell models. IDA and DOX SLNs were developed from warm microemulsion precursors comprising emulsifying wax as the oil phase, and polyoxyl 20-stearyl ether (Brij 78) and D-alpha-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) as the surfactants. Anionic ion-pairing agents, sodium taurodeoxycholate (STDC) and sodium tetradecyl sulfate (STS), were used to neutralize the charges of the cationic anthracyclines and enhance entrapment of the drugs in the SLN. The in-vitro cytotoxicity results showed that the IC50 value of DOX NPs was 9-fold lower than that of free DOX solution in resistant P388/ADR cell line. In contrast, free IDA had comparable IC50 values as IDA NPs in Pgp-overexpressing P388/ADR and HCT-15 cells. In the in-vivo P388/ADR leukemia mouse model, the median survival time of DOX NPs was significantly greater than that of free DOX, and controls. In contrast, free IDA was equally as effective as IDA NPs in P388 and Pgp-overexpressing HCT-15 mouse tumor models. The cell uptake of IDA formulated as free IDA and IDA NPs was comparable in Pgp-overexpressing cells. In conclusion, DOX NPs could overcome Pgp-mediated MDR both in-vitro in P388/ADR leukemia cells and in-vivo in the murine leukemia mouse model. The present study suggests that our SLNs may offer potential to deliver anticancer drugs for the treatment of Pgp-mediated MDR in leukemia; however, selection of target drug may be very important.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.