Drug

As a matter of fact, the drug synthesis process could take years of trial and error to avoid any negative effects. For that, we designed our systems using natural proteins and cascades that the human body employs. We also created the protease with a switchable mechanism to control its activity and added a delivery system to control the release and targeting of the medicine for further safety.

As for loading our synthesised pharmaceuticals, several nanoparticles were chosen based on the drug target and safety considerations. Nano-carriers were chosen based on several criteria, including their ability to cross the blood-brain barrier, route of administration, biocompatibility, biodegradability, low toxicity and high stability, ease of handling and synthesis, low cost, particle size, encapsulation efficiency, and therapeutic effect on Alzheimer's models.

Four nano-carriers satisfied our requirements: PLGA, chitosan, RBCs, and mesoporous silica.

Chitosan

Chitosan is a thoroughly studied polymer with beneficial biological and chemical characteristics like mucoadhesion and ease of functionalization. Drugs can easily pass through the BBB owing to ionic interactions between chitosan-based nanocarriers (CsNCs) and endothelial cells. Since chitosan contains reactive amino and hydroxyl groups, alterations to its structure help to speed up this reaction even further.

Finally, in vivo and in vitro studies have shown that CsNCs have improved passage through the BBB by permanently binding ligands or molecules, such as antibodies or lipids.

PLGA NPs

Poly (lactic-co-glycolic acid) nanoparticles are biocompatible, non-toxic, and have several advantages over other nanomaterials. These advantages include improved drug solubility, protection against enzyme digestion, enhanced targeting, and improved cellular uptake. PLGA NPs offer many advantages for NDD treatments due to their incredible functionality and small size via various available administration routes, such as stereotaxic surgery, which bypasses the BBB and delivers the drugs directly to the target without peripheral drug inactivation, which is considered an invasive technique.

Other methods, such as enteral and parenteral, cross the BBB using different processes, with a first pass effect that reduces the drug concentration when using the enteral route. Another effective method is the intranasal routes, which exhibit an intraneuronal absorption by a direct nose to brain delivery of the NP platforms, which allow rapid and significant active substance passage into the systemic circulation without first-pass metabolism, avoiding drug degradation.

RBCNPs

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, as well as the long circulation time allowed by specific surface receptors that inhibit immune clearance. The incompatibility of different blood types may be a major issue. Specific surface antigens, like sugars, are necessary for the formation of each human blood group. This issue must be taken into account during administration.

Nanoparticles of mesoporous silica

The programmable diffusional release of drug molecules from the highly structured mesoporous structure results in a biogenic local concentration at the targeted site, lowering total dosage and preventing any acute or chronic problems. Furthermore, MSNs can successfully shield medications against premature release before they reach their intended target.

Optimization of Dose

We want to optimise the dosages based on the chosen nanocarrier since it is mostly determined by the encapsulation efficiency and release rate of the nanocarrier, and we will consider the stages of Alzheimer's because they differ in misfolded protein concentration and effect. We will also incorporate parameters such as the BBB rate penetration.

With all these factors, we succeeded in facing such challenges. Knowing that our drug is originally cloned in bacteria, we had mimicked these proteins' environment with that of the ones located in the human brain, furthermore, we meticulously designed our circuit to avoid their side effects, but also no inflammations will occur after degrading Tau and Beta amyloid aggregates. Moreover, our system is distinguished by its ability to be a switchable system, hence it has zero off-target effect in the absence of tau or beta amyloid aggregates.

Smart Watch

Scientifically based, the peptide fragment of beta amyloid degradation in blood is a biomarker for Alzheimer’s. For that we will use one of our binding peptide collections as a sensor for detection. There are a number of end-users that can be targeted to use the smart watch, especially people having family history with the disease as researches showed that they are more likely to develop the disease at earlier ages.

Likewise, people with more than one first-degree relative with Alzheimer’s are at an even higher risk. When diseases like Alzheimer’s and other dementias tend to run in families, either genetics (hereditary factors), environmental factors — or both — may increase the risk for AD, last but not least user’s who have tested positive for APOE4 [1] Risk-factor genetic test. The smartwatch will give those people a clear warning or signal acting as an immediate checkup, because this person could be susceptible to an early or late stage of the disease [2].

Furthermore, the software may be configured to deliver messages reminding users to maintain a healthy daily routine in order to assist them avoid Alzheimer’s. This smartwatch is designed for everyone, especially those with a history of sickness[3].

Software

In our dry-lab work, we experienced issues such as modeling trimerized proteins and mis-folded proteins, in addition to tedious work due to either filtering large number of protein models or narrowing down the target-binding peptides libraries, thus in order to relieve some of the filtering issues and lessen the workload, we created a user-friendly software that functions as a pipeline for our work. We standardized the codes so that the user could use them.

This will simplify the procedure for everyone who works with the area of Drug design. Our pipeline could be perfectly implemented in the process of discovering target binder for dysfunctionally-aggregated proteins hence, any kind of dementia, or proteins having the propensity to trimerize. Simply enter your amino acid sequence into the programme and select the job you want, such as assembly, modelling, QA, Docking, MD, and post MD analysis.

Nevertheless, you can check the user's guide for every single pipeline code. Moreover, we have introduced a function that allows you to upload your own libraries to be tested and ranked by our software.

In conclusion, our software allows the user to run jobs of our system tested on Alzheimer’s and leaves his options wide open to screen for other effective binding targets for different types of Dementia.