The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. The assessment of ex vivo permeation during the pharmaceutical development process helps in understanding the product quality and performance of a transdermal delivery system. Generally, excised human skin relevant to the application site or animal skin is recommended for ex vivo permeation studies. However, the limited availability of the human skin and ethical issues surrounding the use of animal skin rendered these models less attractive in the permeation study. In the last three decades, enormous efforts have been put into developing artificial membranes and 3D cultured human skin models as surrogates to the human skin. This manuscript provides an insight on the European Medicines Agency (EMA) guidelines for permeation studies and the parameters affected when using Franz diffusion cells in the permeation study. The need and possibilities for skin alternatives, such as artificially cultured human skin models, parallel artificial membrane permeability assays (PAMPA), and artificial membranes for penetration and permeation studies, are comprehensively discussed.

Chemotherapeutic drugs are primarily administered to cancer patients via oral or parenteral routes. The use of transdermal drug delivery could potentially be a better alternative to decrease the dose frequency and severity of adverse or toxic effects associated with oral or parenteral administration of chemotherapeutic drugs. The transdermal delivery of drugs has shown to be advantageous for the treatment of highly localized tumors in certain types of breast and skin cancers. In addition, the transdermal route can be used to deliver low-dose chemotherapeutics in a sustained manner. The transdermal route can also be utilized for vaccine design in cancer management, for example, vaccines against cervical cancer. However, the design of transdermal formulations may be challenging in terms of the conjugation chemistry of the molecules and the sustained and reproducible delivery of therapeutically efficacious doses. In this review, we discuss the nano-carrier systems, such as nanoparticles, liposomes, etc., used in recent literature to deliver chemotherapeutic agents. The advantages of transdermal route over oral and parenteral routes for popular chemotherapeutic drugs are summarized. Furthermore, we also discuss a possible in silico approach, Formulating for Efficacy™, to design transdermal formulations that would probably be economical, robust, and more efficacious.

Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug–loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin–loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells.

Antibiotic-resistant bacteria may result in serious infections which are difficult to treat. In addition, the poor antibiotic pipeline has contributed to the crisis. Recently, a complex of furosemide and silver (Ag-FSE) has been reported as a potential antibacterial agent. However, its poor aqueous solubility is limiting its activity. The purpose of this study was to encapsulate Ag-FSE into chitosan nanoparticles (CSNPs) and evaluate antibacterial efficacy. Ag-FSE CSNPs were prepared using an ionic gelation technique. The particle size, polydispersity index, and zeta potential of Ag-FSE CSNPs were 197.1 ± 3.88 nm 0.234 ± 0.018 and 36.7 ± 1.78 mV, respectively. Encapsulation efficiency was 66.72 ± 4.14%. In vitro antibacterial activity results showed that there was 3- and 6-fold enhanced activity with Ag-FSE CSNPs against E. coli and S. aureus, respectively. Results also confirmed that Ag-FSE CSNPs showed ~44% release within 4 h at pH 5.5 and 6.5. Moreover, release from the CSNPs was sustained with a cumulative release of ~75% over a period of 24 h. In conclusion, encapsulation of Ag-FSE into CSNPs resulted in significant improvement of antibacterial efficacy with a sustained and pH-sensitive release. Therefore, Ag-FSE CSNPs can be considered as a potential novel antibacterial agent against bacterial infections.

A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC₅₀ values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC₅₀ of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

In men, prostate cancer (PC) is the most frequently diagnosed cancer, causing an estimated 375,000 deaths globally. Currently, existing therapies for the treatment of PC, notably metastatic cases, have limited efficacy due to drug resistance and problematic adverse effects. Therefore, it is imperative to discover and develop novel drugs for treating PC that are efficacious and do not produce intolerable adverse or toxic effects. Condensed quinolines are naturally occurring anticancer compounds. In this study, we determined the in vitro efficacy of IND-2 (4-chloro-2-methylpyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinolone) in the PC lines, PC-3 and DU-145. IND-2 significantly inhibited the proliferation of PC-3 and DU-145, with IC₅₀ values of 3 µM and 3.5 µM, respectively. The incubation of PC-3 cells with 5 and 10 µM of IND-2 caused the loss of the mitochondrial membrane potential in PC-3 cells. Furthermore, IND-2, at 5 µM, increased the expression of cleaved caspase-3, cleaved caspase-7 and cleaved poly (ADP-ribose) polymerase (PARP). The incubation of PC-3 cells with 5 µM of IND-2 significantly decreased the expression of the apoptotic protein, B-cell lymphoma 2 (Bcl-2). Furthermore, 5 and 10 µM of IND-2 produced morphological changes in PC-3 cells characteristic of apoptosis. Interestingly, IND-2 (2.5, 5 and 10 µM) also induced mitotic catastrophe in PC-3 cells, characterized by the accumulation of multinuclei. The incubation of DU-145 cells with 1.25 and 5 μM of IND-2 significantly increased the levels of reactive oxygen species (ROS). Finally, IND-2, at 10 μM, inhibited the catalytic activity of topoisomerase IIα. Overall, our findings suggest that IND-2 could be a potential lead compound for the development of more efficacious compounds for the treatment of PC.