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Background Paclitaxel administration causes peripheral neuropathy. Auraptene is a natural bioactive monoterpene with anti-inflammatory and anti-neuropathic effects that is widely used.Objectives We aimed to study auraptene effects on paclitaxel-induced neuropathy.Materials and Methods This study was comprised of two steps of evaluation of the preventive and treatment effects of auraptene in mice. In the first step, mice were randomly allocated into three groups of six animals, including the negative control (NEG CTL): animals injected with paclitaxel (PTX) together with normal saline, PTX (paclitaxel 2 mg/kg given on days 1, 3, 5, and 7), and PREVENTION: PTX + auraptene 100 mg/kg on days 1, 3, 5, and 7. In the second step, animals were allocated into six groups of six: NEG CTL (normal saline), PTX (paclitaxel 10 mg/kg given on days 1, 3, 5, and 7), PTX AUR (PTX + auraptene 50, 75, and 100 mg/kg), and a positive control (PTX-treated animals receiving imipramine 10 mg/kg). Intraperitoneal injection of PTX 2 mg/kg on days 1, 3, 5, and 7 was used in order to induce neuropathy. In both steps of the study, a hot plate test was done on day 7 in order to determine the response to heat. After the scarification of animals, the interleukin-6 (IL-6) level in the sciatic nerve was assessed by western blotting.Results In the preventive group, auraptene could reduce hyperalgesia significantly. In the treatment step, the AUR 100 mg/kg compared to NEG CTL groups had significantly increased heat latency. The expression of IL-6 protein in the sciatic nerve was remarkably decreased in both the preventive and treatment groups compared to NEG CTL.Conclusion Taken together, our results confirmed that AUR could decrease paclitaxel-induced hyperalgesia in mice and IL-6 protein content in sciatic nerve samples.

Supramolecular carriers as a targeted drug delivery system have a significant role in managing the pharmacokinetics and pharmacodynamics of drugs. Therefore, in this project, we used cyclodextrin (CD) as a host molecule for tamoxifen (TMX) and methotrexate (MTX) to evaluate apoptosis mechanism and statistical patterns of release. The flow cytometry analysis showed that combination therapy by anticancer drugs was successful in apoptosis induction compared to free TMX and MTX. Also, real-time PCR and western blot analyses were performed to measure gene expression of Bak1, Bclx, and caspase-3 in estrogen and folate receptor-positive MCF-7 cell lines. All results confirmed that MNPs containing TMX and MTX can significantly increase Bak1/Bclx ratios plus the activity of caspase-3, while free MTX and free TMX showed no effects on triggering apoptosis after 24 h of exposure. According to results of pharmacokinetic studies onto TMX and MTX release, it is revealed that both models that consist of Sahlin-Peppas and Ritger-Peppas create the good fitting curves more than other statistical patterns at both low and high temperatures (37°C and 42°C). For this reason, activation parameters (ΔH‡, ΔS‡, and ΔG‡) were calculated to estimate the favorable model. The lower energy barrier indicates that the Sahlin-Peppas is the favorable model with both diffusion and relaxation process. Therefore, combination therapy by two anticancer drugs, TMX and MTX, utilizing cyclodextrin-based host–guest supramolecular magnetic nanoparticles (CD-MNPs) provided new results for induction of apoptosis and pharmacokinetic model.

Prediction of pharmacokinetics and drug targeting is a challenge in drug design. There are different types of software that can help to predict the pharmacokinetic profile of a drug. Quantitative structure-activity relationship (QSAR) modeling is used for drug design with less cost. Drug-excipient interactions are predicted by docking tools. Computerized drug target prediction and docking programs offer additional options to predict potential effects and adverse reactions of a given candidate as well as the best orientation of the compound on the receptor active site. Information on the absorption, distribution, metabolism and excretion of the drug in the body can enhance prediction of drug release and distribution in the blood and central nervous system (CNS). Computer- aided drug design and delivery can help to save the time and cost in the process of rational drug development.