Sijongesonke Peter

Neurological-related diseases are among the most debilitating and difficult to manage. Many possible pharmacological treatments for neurological diseases struggle to cross the blood–brain barrier (BBB) to achieve concentrations that can produce a therapeutic benefit. This is primarily because of the existence of the BBB, which poses significant hurdles for both therapeutic and diagnostic efforts by restricting the entry of most medications. Nasal-to-brain drug transportation has surfaced as an encouraging approach to tackle the difficulties linked with conventional drug administration techniques for neurological disorders. In response, innovative methods for improving drug delivery focus on breaking down the BBB via physical techniques, including optical and photothermal therapy, electrical stimulation, and acoustic or mechanical stimulation. Nanocarriers represent a promising approach for facilitating nasal systemic and brain delivery of active compounds. Hence, the achievement of therapeutically relevant concentrations of exogenous molecules within the body is significantly contingent upon the nanocarriers’ capability to surpass biological barriers. Polymers in nanocarrier formulations can result in significantly enhanced nose-to-brain drug delivery by protecting drugs from premature biodegradation, increasing permeability, improving mucoadhesion, and targeting specific cells in the brain. Polymeric nanocarriers are frequently functionalized with cell-penetrating peptides to further improve the specificity of the loaded therapeutic molecules. This review focuses on the use of nanocarrier-based therapeutic agents to enhance the efficacy of nose-to-brain delivery systems.

Background/Objectives: Cancer and bacterial cases are increasing. Hence, new drugs to treat these diseases are paramount. Ferrocene-based hybrid compounds were synthesizedas potential cancer and bacteria therapeutics. Methods: The synthesized compounds were characterized via FTIR, NMR, and LC-MS and evaluated against different cancer cells and bacterial strains. Moreover, computational studies of these compounds were conducted using several silico tools. Results: Among the synthesized compounds, hybrid 10 was the most promising compound, displaying promising anticancer activity with IC₅₀ values between 42.42 and 45.37 and 50.64 and 73.37 µg/mL against HeLa and CHO cancer cells, respectively, with a selective index greater than one on HeLa cancer cells. Compounds 22–26 displayed promising antibacterial activity with a MIC value of 7.8125 µg/mL against most bacterial strains in vitro. The in silico results revealed that this compound has strong binding affinities for 4qtb, 3eqm, and 2w3l cervical cancer proteins, exhibiting binding energies of −7.3, −8.7, and 7.4 kcal/mol, respectively. Furthermore, hybrid 10 showed promising pharmacokinetics and drug-like properties, including high GI absorption, moderate water solubility, favoring the oral administration route, nontoxicity, and is a P-gp substrate. Conclusions: The findings obtained in this study illustrate that hybrid compounds are potential therapeutics that need to be explored. The compounds also contained functionalities relevant for incorporating into nanocarriers to improve their biological activities further. Therefore, further studies are recommended for the most effective compounds to reinforce these findings.

There are different types of cancer treatments, including surgery, radiotherapy, and chemotherapy. However, the complexity of cancer has resulted in treatment challenges to medicinal scientists and a socio-economic burden to the public health system globally. The pharmacological limitations associated with the current conventional anticancer drugs include lack of specificity, poor bioavailability, toxicity, drug resistance, and poor delivery mechanisms, which make cancer treatment challenging. Thus, the number of cancer cases is escalating rapidly, especially breast and prostate cancer in women and men, respectively. The application of nanoformulations is gaining momentum for treating different cancer types. However, they also exhibit challenges that must be addressed for effective cancer treatment. Nanoliposomes are nanoformulations that are widely explored for cancer treatment with interesting therapeutic outcomes. They have been functionalized with PEG to further improve their therapeutic outcomes. Hence, this review provides an update on PEGylated nanoliposomes loaded with anticancer drugs for the treatment of breast and prostate cancer, focusing on pre-clinical studies published in the last decade (2015 to 2024) to reflect the recent advancements made in the design of PEGylation nanoliposomes. Highlights of the clinically and commercially available PEGylation nanoliposomes are also presented in this review.

Cancer is ranked among lethal diseases globally, and the increasing number of cancer cases and deaths results from limited access to effective therapeutics. The use of plant-based medicine has been gaining interest from several researchers. Carvacrol and its isomeric compound, thymol, are plant-based extracts that possess several biological activities, such as antimalarial, anticancer, antifungal, and antibacterial. However, their efficacy is compromised by their poor bioavailability. Thus, medicinal scientists have explored the synthesis of hybrid compounds containing their pharmacophores to enhance their therapeutic efficacy and improve their bioavailability. Hence, this review is a comprehensive report on hybrid compounds containing carvacrol and its isomer, thymol, with potent anticancer and antibacterial agents reported between 2020 and 2024. Furthermore, their structural activity relationship (SAR) and recommended future strategies to further enhance their therapeutic effects will be discussed.

Background:: The concept of utilizing drug repurposing/repositioning in the development of hybrid molecules is an important strategy in drug discovery. Fluoroquinolones, a class of antibiotics, have been reported to exhibit anticancer activities. Although anticancer drug development is achieving some positive outcomes, there is still a need to develop new and effective anticancer drugs. Some limitations associated with most of the available anticancer drugs are drug resistance and toxicity, poor bio-distribution, poor solubility, and lack of specificity, which hamper their therapeutic outcomes. Objectives:: Fluoroquinolones, a known class of antibiotics, have been explored by hybridizing them with other pharmacophores and evaluating their anticancer activity in silico and in vitro. Hence, this review provides an update on new anticancer drugs development containing fluoroquinolones moiety, Ciprofloxacin and Norfloxacin between 2020 and 2023, their structural relationship activity, and the future strategies to develop potent chemotherapeutic agents. Methods:: Fluoroquinolones were mostly hybridized via the N-4 of the piperazine ring on position C-7 with known pharmacophores characterized, followed by biological studies to evaluate their anticancer activity. Results:: The hybrid molecules displayed promising and interesting anticancer activities. Factors such as the nature of the linker, the presence of electron-withdrawing groups, nature, and position of the substituents influenced the anticancer activity of the synthesized compounds Conclusion:: The hybrids were selective towards some cancer cells. However, further in vivo studies are needed to fully understand their mode of action

Increasing cases of cancer have been a primary concern in recent decades. Developing new chemotherapeutics is challenging and has been faced with limitations, such as multidrug resistance, poor specificity, selectivity, and toxicity. The aforementioned factors contribute to treatment failure. Hybrid compounds have features that can overcome the limitations mentioned above. Chlorambucil, an anticancer drug that is used to treat prostate and breast cancer, suffers from poor aqueous solubility and specificity, a short half-life, and severe side effects, including anaemia and bone marrow suppression. It compromises the immune system, resulting in treatment failure. Hence, its combination with other pharmacophores has been reported to result in effective anticancer agents with fewer side effects and high therapeutic outcomes. Furthermore, this review gives an update (2010 to date) on the developments of chlorambucil hybrid compounds with anticancer activity, and the structure-activity relationship (SAR), and also highlights future strategies for developing novel anticancer agents.

Among the factors that delay the wound healing process in chronic wounds, bacterial infections are a common cause of acute wounds becoming chronic. Various therapeutic agents, such as antibiotics, metallic nanoparticles, and essential oils have been employed to treat infected wounds and also prevent the wounds from bacterial invasion. Essential oils are promising therapeutic agents with excellent wound healing, anti-inflammatory and antimicrobial activities, and good soothing effects. Some essential oils become chemically unstable when exposed to light, heat, oxygen, and moisture. The stability and biological activity of essential oil can be preserved via loading into hydrogels. The polymer-based hydrogels loaded with bioactive agents are regarded as ideal wound dressings with unique features, such as controlled and sustained drug release mechanisms, good antibacterial activity, non-toxicity, excellent cytocompatibility, good porosity, moderate water vapour transmission rate, etc. This review addresses the pre-clinical outcomes of hydrogels loaded with essential oils in the treatment of infected wounds.

The scarcity of novel and effective therapeutics for the treatment of cancer is a pressing and alarming issue that needs to be prioritized. The number of cancer cases and deaths are increasing at a rapid rate worldwide. Doxorubicin, an anticancer agent, is currently used to treat several types of cancer. It disrupts myriad processes such as histone eviction, ceramide overproduction, DNA-adduct formation, reactive oxygen species generation, Ca²⁺, and iron hemostasis regulation. However, its use is limited by factors such as drug resistance, toxicity, and congestive heart failure reported in some patients. The combination of doxorubicin with other chemotherapeutic agents has been reported as an effective treatment option for cancer with few side effects. Thus, the hybridization of doxorubicin and other chemotherapeutic drugs is regarded as a promising approach that can lead to effective anticancer agents. This review gives an update on hybrid compounds containing the scaffolds of doxorubicin and its derivatives with potent chemotherapeutic effects.

Diabetic wounds are severe injuries that are common in patients that suffer from diabetes. Most of the presently employed wound dressing scaffolds are inappropriate for treating diabetic wounds. Improper treatment of diabetic wounds usually results in amputations. The shortcomings that are related to the currently used wound dressings include poor antimicrobial properties, inability to provide moisture, weak mechanical features, poor biodegradability, and biocompatibility, etc. To overcome the poor mechanical properties, polymer-based wound dressings have been designed from the combination of biopolymers (natural polymers) (e.g., chitosan, alginate, cellulose, chitin, gelatin, etc.) and synthetic polymers (e.g., poly (vinyl alcohol), poly (lactic-co-glycolic acid), polylactide, poly-glycolic acid, polyurethanes, etc.) to produce effective hybrid scaffolds for wound management. The loading of bioactive agents or drugs into polymer-based wound dressings can result in improved therapeutic outcomes such as good antibacterial or antioxidant activity when used in the treatment of diabetic wounds. Based on the outstanding performance of polymer-based wound dressings on diabetic wounds in the pre-clinical experiments, the in vivo and in vitro therapeutic results of the wound dressing materials on the diabetic wound are hereby reviewed.