Synchronizing In Silico, In Vitro, and In Vivo Studies for the Successful Nose to Brain Delivery of an Anticancer Molecule

Abstract

Sesamol is a sesame seed constituent with reported activity against many types of cancer. In this work, two types of nanocarriers, solid lipid nanoparticles (SLNs) and polymeric nanoparticles (PNs), were exploited to improve sesamol efficiency against the glioma cancer cell line. The ability of the proposed systems for efficient brain targeting intranasally was also inspected. By the aid of two docking programs, the virtual loading pattern inside these nanocarriers was matched to the real experimental results. Interactions involved in sesamol–carrier binding were also assessed, followed by a discussion of how different scoring functions account for these interactions. The study is an extension of the computer-assisted drug formulation design series, which represents a promising initiative for an upcoming industrial innovation. The results proved the power of combined in silico tools in predicting members with the highest sesamol payload suitable for delivering a sufficient dose to the brain. Among nine carriers, glyceryl monostearate (GMS) and polycaprolactone (PCL) scored the highest sesamol payload practically and computationally. The EE % was 66.09 ± 0.92 and 61.73 ± 0.47 corresponding to a ΔG (binding energy) of −8.85 ± 0.16 and −5.04 ± 0.11, respectively. Dynamic light scattering evidenced the formation of 215.1 ± 7.2 nm and 414.25 ± 1.6 nm nanoparticles, respectively. Both formulations demonstrated an efficient cytotoxic effect and brain-targeting ability compared to the sesamol solution. This was evidenced by low IC50 (38.50 ± 10.37 μM and 27.81 ± 2.76 μM) and high drug targeting efficiency (7.64 ± 1.89-fold and 13.72 ± 4.1-fold) and direct transport percentages (86.12 ± 3.89 and 92.198 ± 2.09) for GMS-SLNs and PCL-PNs, respectively. The results also showed how different formulations, having different compositions and characteristics, could affect the cytotoxic and targeting ability.

Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

“…Sesamol, a potential candidate for the treatment of glial cancer, was incorporated into SLNs for nose-to-brain delivery [ 114 ]. SLNs (IN) had a shorter T max,brain (10 min versus 30 min) and a higher C max,brain (13.2-fold) than the free drug (IV).…”

Design, development, in-vitro and in-vivo evaluation of polylactic acid-based multifunctional nanofibrous patches for efficient healing of diabetic wounds

“…Many polymers have been approved by FDA for various biomedical applications including: (i) drug delivery such as anticancer, immunotherapy 24 , 41 – 45 , etc., (ii) tissue engineering 21 , 29 , 46 and (iii) wound healing 21 , 29 owing to their facile formulations, biocompatibility, biodegradability, etc. Many polymers have been used in fabricating NFs either natural-based such as chitosan, gelatin and collagen, or synthetic such as polyvinyl alcohol, polycaprolactone and others.…”

Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid–Polymer Hybrid Nanocarriers

“…Although there was no clear mechanism demonstrating the nose-to-brain delivery pathway, many studies investigated the high nasal mucosa permeability as well as the olfactory and trigeminal nerve pathways, which were the most suggested approaches for nose-to-brain delivery [ 8 , 9 , 10 , 11 ]. Furthermore, it is proven that the IN administration of different nanocarriers improves the bioavailability of different CNS drugs by circumventing the BBB and protecting the payloads from degradation [ 12 , 13 , 14 , 15 , 16 ].…”