The blood-brain barrier: Physiology and strategies for drug delivery.

Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood-brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors. 

/pdf/overcoming-the-blood-brain-barrier-for-the-therapy-of-3p99aigd.pdf

Overcoming the blood–brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches

Natural products derived from plants, as well as their bioactive compounds, have been extensively studied in recent years for their therapeutic potential in a variety of neurodegenerative diseases (NDs), including Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease. These diseases are characterized by progressive dysfunction and loss of neuronal structure and function. There has been little progress in designing efficient treatments, despite impressive breakthroughs in our understanding of NDs. In the prevention and therapy of NDs, the use of natural products may provide great potential opportunities; however, many clinical issues have emerged regarding their use, primarily based on the lack of scientific support or proof of their effectiveness and patient safety. Since neurodegeneration is associated with a myriad of pathological processes, targeting multi-mechanisms of action and neuroprotection approaches that include preventing cell death and restoring the function of damaged neurons should be employed. In the treatment of NDs, including AD and PD, natural products have emerged as potential neuroprotective agents. This current review will highlight the therapeutic potential of numerous natural products and their bioactive compounds thatexert neuroprotective effects on the pathologies of NDs.

Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges.

DFT, NBO, HOMO-LUMO, NCI, stability, Fukui function and hole – Electron analyses of tolcapone

Prodrugs are inactive precursors of an active drug designed to be bioconverted (activated) post administration with the main aim of improving the pharmacokinetic properties of the parent drug. Prod...

https://www.tandfonline.com/doi/pdf/10.1080/17425247.2019.1553954

The prodrug approach in the era of drug design.

Background: Parkinson’s disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals. Results: A promising ester prodrug for intranasal delivery has been developed. LD methyl ester is currently in Phase III clinical trials. A series of amide prodrugs were synthesized with better stability than ester prodrugs. Both amide and dimeric amide prodrugs offer enhanced blood brain barrier (BBB) penetration and better pharmacokinetics. Attaching LD to sugars has been used to exploit glucose transport mechanisms into the brain. Conclusions: Till now, no DA prodrug has reached the pharmaceutical market, nevertheless, the future of utilizing prodrugs for the treatment of PD seems to be bright. For instance, LD ester prodrugs have demonstrated an adequate intranasal delivery of LD, thus enabling the absorption of therapeutic agents to the brain. Most of the amide, cyclic, peptidyl or chemical delivery systems of DA prodrugs demonstrated enhanced pharmacokinetic properties.

/pdf/dopamine-and-levodopa-prodrugs-for-the-treatment-of-snql1x4ygu.pdf

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease.

Adenosine triphosphate (ATP) is critical for all life from the simplest to the most complex. All organisms from the microscopic to humans utilize ATP as the source for their primary energy currency. This manuscript describes a novel method to calculate the number of ATP molecules generated from the consumption of any sugar (having 3-7 carbons). This calculation method based on the oxidation states of the sugar’s carbons. The time needed to calculate the number of ATP molecules by this method is less than 2 minutes whereas that required by the current (regular) method is many hours and even days in some cases. In addition, the current method requires drawing all biochemical processes that the sugar undergoes upon its cellular respiration (oxidation) while our method described herein does not.

A Novel Mathematical Equation For Calculating The Number of ATP Molecules Generated From Sugars In Cells

Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies

Plasma Protein Binding Refinement of the Extended Clearance Classification System: Subclasses for Predicting Hepatic Uptake or Renal Clearance for Classes 1B and 3B

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Papers

Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease.

A Novel Mathematical Equation For Calculating The Number of ATP Molecules Generated From Sugars In Cells

Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies

Plasma Protein Binding Refinement of the Extended Clearance Classification System: Subclasses for Predicting Hepatic Uptake or Renal Clearance for Classes 1B and 3B