Chitosan-Based Scaffolds Incorporated with Silver Nanoparticles for the Treatment of Infected Wounds.

Bacterial infections are major problems in wound care due to their impact on the retarded process of wound healing, leading to chronic wounds. Most of the presently utilized wound dressing products exhibit poor antimicrobial properties. Wound dressings formulated from chitosan have been reported to be effective for treating infected wounds, resulting from the antibacterial properties of chitosan. The antibacterial properties of chitosan-based wound dressings can be further enhanced by incorporating metallic nanoparticles into them, such as silver, zinc, titanium, etc. The incorporation of silver nanoparticles into chitosan-based wound dressings has been widely explored in the design of antimicrobial wound dressings. The incorporation of silver nanoparticles into chitosan-based wound dressings promotes accelerated wound-healing processes due to enhanced antimicrobial activity. The accelerated wound healing by these metal-based nanoparticles is via the regulation of re-epithelialization and inflammation without affecting the viability of normal cells. However, there have been few reports that evaluate these wound dressings in infectious animal models to prove their efficacy. The in vivo toxicity of silver nanoparticles still needs to be addressed, revealing the need for further preclinical and clinical trials. The fabrication of wound dressings incorporated with silver nanoparticles has not been fully explored, especially for wounds requiring immediate treatment. The possible interactions between silver nanoparticles and chitosan scaffolds that result in synergistic effects still need to be understood and studied. This review provides a comprehensive report on the preclinical outcomes of chitosan wound dressing materials loaded with silver nanoparticles for managing infected wounds.

Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties.

BACKGROUND: There is a critical need for the discovery of novel and effective antibacterial or anticancer molecules. OBJECTIVES: Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%. METHODS: Their molecular structures were successfully confirmed using different spectroscopic methods including 1H/13C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method. RESULT: Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 µg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC50 value of 43.64 g/mL. CONCLUSION: The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required.

Nanotherapeutics for the delivery of antifungal drugs.

The treatment of fungal infections is challenging with high death rates reported among immunocompromised patients. The currently available antifungals suffer from poor bioavailability and solubility, pharmacokinetics, and drug resistance, with limited cellular uptake. The clinical pipeline of new antifungals is dry. The incorporation of antifungal drugs into polymer-based nanocarriers to form nanotherapeutics is a promising approach to enhance the therapeutic outcomes of the available antifungal drugs. This review summarizes different polymer-based nanotherapeutics strategies that have been explored for the delivery of antifungals, resulting in enhanced therapeutic outcomes, such as improved pharmacokinetics, targeted/sustained delivery, prolonged drug circulation, retention of the drugs at the localized site of action, and overcoming drug resistance when compared with the free antifungal drugs.

Some fungi are more powerful than the drugs that should destroy them. These drugs are known as antifungal drugs. Some of these drugs do not dissolve well in water, some make the people sicker, and very small amounts reach the fungi inside the body after giving the drugs to sick people. To help make these drugs destroy the fungi in the body, they are put into very small molecules ­ known as polymers. However, how they work is not well known. This review discusses different polymer molecules, and what research has shown so far about how effective they are at delivering drugs to fight fungal infections.

Chlorambucil-Bearing Hybrid Molecules in the Development of Potential Anticancer Agents.

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.

Carboxymethyl cellulose/poloxamer gels enriched with essential oil and Ag nanoparticles: promising wound dressings.

Aim: Essential oils are promising antibacterial and wound-healing agents that should be explored for the design of wound dressings. Materials & methods: Topical gels prepared from a combination of carboxymethyl cellulose and poloxamer were incorporated with tea tree and lavender oil together with Ag nanoparticles. In vitro release, cytotoxicity, antibacterial, and wound healing studies were performed. Results: The gels displayed good spreadability with viscosity in the range of 210-1200 cP. The gels displayed promising antibacterial activity against selected Gram-positive and Gram-negative bacteria used in the study. The % cell viability of the gels was more than 90.83%. Conclusion: The topical gels displayed excellent wound closure in vitro revealing that they are potential wound dressings for bacteria-infected wounds.

What is this article about? This article reports the efficacy of carboxymethyl cellulose-based topical gels loaded with a combination of essential oils and silver nanoparticles as potential wound dressings for bacterial-infected wounds. What were the results? The topical gels induced a faster rate of closure than the untreated cells in 96 h. The gel formulations did not induce any significant cytotoxic effect. They were effective against Gram-negative and Gram-positive bacteria used in the study. What do the results of the study mean? The topical gels displayed promising healing effects in vitro revealing that they are potential wound dressings for treating bacteria-infected wounds.

Polymer drug conjugates containing memantine, tacrine and cinnamic acid: promising nanotherapeutics for the treatment of Alzheimer's disease.

AIM: To prepare polymer-drug conjugates containing a combination of memantine, tacrine, and E)-N-(3-aminopropyl)cinnamide, promising therapeutics for the treatment of neurodegenerative disorders. METHODS: The conjugates were characterised by 1HNMR, particle size analysis, SEM, LC-MS, TEM/EDX, and XRD, followed by in vitro anti-acetylcholinesterase and drug release studies. RESULTS: 1H NMR analysis revealed successful drug conjugation with drug mass percentages in the range of 1.3-6.0% w/w. The drug release from the conjugates was sustained for 10 h in the range of 20-36%. The conjugates' capability to inhibit acetylcholinesterase (AChE) activity was significant with IC50 values in the range of 13-44.4 µm which was more effective than tacrine (IC50 =1698.8 µm). The docking studies further confirmed that the conjugation of the drugs into the polymer improved their anti-acetylcholinesterase activity. CONCLUSION: The drug release profile, particle sizes, and in vitro studies revealed that the conjugates are promising therapeutics for treating neurodegenerative disorders.

Gellan Gum in Wound Dressing Scaffolds.

Several factors, such as bacterial infections, underlying conditions, malnutrition, obesity, ageing, and smoking are the most common issues that cause a delayed process of wound healing. Developing wound dressings that promote an accelerated wound healing process and skin regeneration is crucial. The properties of wound dressings that make them suitable for the acceleration of the wound healing process include good antibacterial efficacy, excellent biocompatibility, and non-toxicity, the ability to provide a moist environment, stimulating cell migration and adhesion, and providing gaseous permeation. Biopolymers have demonstrated features appropriate for the development of effective wound dressing scaffolds. Gellan gum is one of the biopolymers that has attracted great attention in biomedical applications. The wound dressing materials fabricated from gellan gum possess outstanding properties when compared to traditional dressings, such as good biocompatibility, biodegradability, non-toxicity, renewability, and stable nature. This biopolymer has been broadly employed for the development of wound dressing scaffolds in different forms. This review discusses the physicochemical and biological properties of gellan gum-based scaffolds in the management of wounds.

Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy.

Colorectal cancer is a common cancer in both men and women. Numerous studies on the therapeutic effectiveness of nanoparticles against colorectal cancer have been reported. Platinum treatments as well as other medications comprising of nanoparticles have been utilized. Drug resistance restricts the use of platinum medicines, despite their considerable efficacy against a variety of cancers. This review reports clinically licensed platinum medicines (cisplatin, carboplatin, and oxaliplatin) combined with various nanoparticles that have been evaluated for their therapeutic efficacy in the treatment of colorectal cancer, including their mechanism of action, resistance, and limitations.

Polymer-Based Hydrogels Enriched with Essential Oils: A Promising Approach for the Treatment of Infected Wounds.

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.

Hybrid-Based Wound Dressings: Combination of Synthetic and Biopolymers.

Most commercialized wound dressings are polymer-based. Synthetic and natural polymers have been utilized widely for the development of wound dressings. However, the use of natural polymers is limited by their poor mechanical properties, resulting in their combination with synthetic polymers and other materials to enhance their mechanical properties. Natural polymers are mostly affordable, biocompatible, and biodegradable with promising antimicrobial activity. They have been further tailored into unique hybrid wound dressings when combined with synthetic polymers and selected biomaterials. Some important features required in an ideal wound dressing include the capability to prevent bacteria invasion, reduce odor, absorb exudates, be comfortable, facilitate easy application and removal as well as frequent changing, prevent further skin tear and irritation when applied or removed, and provide a moist environment and soothing effect, be permeable to gases, etc. The efficacy of polymers in the design of wound dressings cannot be overemphasized. This review article reports the efficacy of wound dressings prepared from a combination of synthetic and natural polymers.

Dissolvable wound dressing loaded with silver nanoparticles together with ampicillin and ciprofloxacin.

Aim: The current study is focused on the development of water-soluble wound dressings, which are potential dressings for the treatment of burn wounds. Materials & methods: Sodium alginate-based dissolvable wound dressings were prepared and loaded with silver nanoparticles and various antibiotics (ampicillin and ciprofloxacin) followed by characterization and in vitro antibacterial studies. Results & conclusions: The prepared sodium alginate-based dissolvable wound dressing exhibited good porosity, water uptake and moisture content, promising antibacterial activity, high absorption capacity of simulated wound exudates, excellent water vapor transmission rate in the range of 2000 to 5000 g/m2 day-1, sustained drug-release profiles and water solubility. The wound dressings were active against Proteus mirabilis, Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Klebsiella aeruginosa strains of bacteria. The results obtained revealed the wound dressing as potential wound dressings for burn wounds and sensitive skin.

Doxorubicin-Based Hybrid Compounds as Potential Anticancer Agents: A Review.

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.

Recent Advances in the Therapeutic Efficacy of Artesunate.

Artesunate, a semisynthetic artemisinin derivative, is well-known and used as the first-line drug for treating malaria. Apart from treating malaria, artesunate has also been found to have biological activity against a variety of cancers and viruses. It also exhibits antidiabetic, anti-inflammatory, anti-atherosclerosis, immunosuppressive activities, etc. During its administration, artesunate can be loaded in liposomes, alone or in combination with other therapeutic agents. Administration routes include intragastrical, intravenous, oral, and parenteral. The biological activity of artesunate is based on its ability to regulate some biological pathways. This manuscript reports a critical review of the recent advances in the therapeutic efficacy of artesunate.

Collagen-Based Nanofibers for Skin Regeneration and Wound Dressing Applications.

Skin regeneration after an injury is very vital, but this process can be impeded by several factors. Regenerative medicine is a developing biomedical field with the potential to decrease the need for an organ transplant. Wound management is challenging, particularly for chronic injuries, despite the availability of various types of wound dressing scaffolds in the market. Some of the wound dressings that are in clinical practice have various drawbacks such as poor antibacterial and antioxidant efficacy, poor mechanical properties, inability to absorb excess wound exudates, require frequent change of dressing and fails to offer a suitable moist environment to accelerate the wound healing process. Collagen is a biopolymer and a major constituent of the extracellular matrix (ECM), making it an interesting polymer for the development of wound dressings. Collagen-based nanofibers have demonstrated interesting properties that are advantageous both in the arena of skin regeneration and wound dressings, such as low antigenicity, good biocompatibility, hemostatic properties, capability to promote cellular proliferation and adhesion, and non-toxicity. Hence, this review will discuss the outcomes of collagen-based nanofibers reported from the series of preclinical trials of skin regeneration and wound healing.

Fabrication of Hybrid Nanofibers from Biopolymers and Poly (Vinyl Alcohol)/Poly (ε-Caprolactone) for Wound Dressing Applications.

The management of chronic wounds is challenging. The factors that impede wound healing include malnutrition, diseases (such as diabetes, cancer), and bacterial infection. Most of the presently utilized wound dressing materials suffer from severe limitations, including poor antibacterial and mechanical properties. Wound dressings formulated from the combination of biopolymers and synthetic polymers (i.e., poly (vinyl alcohol) or poly (ε-caprolactone) display interesting properties, including good biocompatibility, improved biodegradation, good mechanical properties and antimicrobial effects, promote tissue regeneration, etc. Formulation of these wound dressings via electrospinning technique is cost-effective, useful for uniform and continuous nanofibers with controllable pore structure, high porosity, excellent swelling capacity, good gaseous exchange, excellent cellular adhesion, and show a good capability to provide moisture and warmth environment for the accelerated wound healing process. Based on the above-mentioned outstanding properties of nanofibers and the unique properties of hybrid wound dressings prepared from poly (vinyl alcohol) and poly (ε-caprolactone), this review reports the in vitro and in vivo outcomes of the reported hybrid nanofibers.

Electrospun Nanofibers/Nanofibrous Scaffolds Loaded with Silver Nanoparticles as Effective Antibacterial Wound Dressing Materials.

The treatment of wounds is expensive and challenging. Most of the available wound dressings are not effective and suffer from limitations such as poor antimicrobial activity, toxicity, inability to provide suitable moisture to the wound and poor mechanical performance. The use of inappropriate wound dressings can result in a delayed wound healing process. Nanosize range scaffolds have triggered great attention because of their attractive properties, which include their capability to deliver bioactive agents, high surface area, improved mechanical properties, mimic the extracellular matrix (ECM), and high porosity. Nanofibrous materials can be further encapsulated/loaded with metal-based nanoparticles to enhance their therapeutic outcomes in wound healing applications. The widely studied metal-based nanoparticles, silver nanoparticles exhibit good properties such as outstanding antibacterial activity, display antioxidant, and anti-inflammatory properties, support cell growth, making it an essential bioactive agent in wound dressings. This review article reports the biological (in vivo and in vitro) and mechanical outcomes of nanofibrous scaffolds loaded with silver nanoparticles on wound healing.

The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment.

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo.

Chitosan and Cellulose-Based Hydrogels for Wound Management.

Wound management remains a challenge worldwide, although there are several developed wound dressing materials for the management of acute and chronic wounds. The wound dressings that are currently used include hydrogels, films, wafers, nanofibers, foams, topical formulations, transdermal patches, sponges, and bandages. Hydrogels exhibit unique features which make them suitable wound dressings such as providing a moist environment for wound healing, exhibiting high moisture content, or creating a barrier against bacterial infections, and are suitable for the management of exuding and granulating wounds. Biopolymers have been utilized for their development due to their non-toxic, biodegradable, and biocompatible properties. Hydrogels have been prepared from biopolymers such as cellulose and chitosan by crosslinking with selected synthetic polymers resulting in improved mechanical, biological, and physicochemical properties. They were useful by accelerating wound re-epithelialization and also mimic skin structure, inducing skin regeneration. Loading antibacterial agents into them prevented bacterial invasion of wounds. This review article is focused on hydrogels formulated from two biopolymers-chitosan and cellulose-for improved wound management.

Polymer-Based Materials Loaded with Curcumin for Wound Healing Applications.

Some of the currently used wound dressings have interesting features such as excellent porosity, good water-absorbing capacity, moderate water vapor transmission rate, high drug loading efficiency, and good capability to provide a moist environment, but they are limited in terms of antimicrobial properties. Their inability to protect the wound from microbial invasion results in wound exposure to microbial infections, resulting in a delayed wound healing process. Furthermore, some wound dressings are loaded with synthetic antibiotics that can cause adverse side effects on the patients. Natural-based compounds exhibit unique features such as good biocompatibility, reduced toxicity, etc. Curcumin, one such natural-based compound, has demonstrated several biological activities such as anticancer, antibacterial and antioxidant properties. Its good antibacterial and antioxidant activity make it beneficial for the treatment of wounds. Several researchers have developed different types of polymer-based wound dressings which were loaded with curcumin. These wound dressings displayed excellent features such as good biocompatibility, induction of skin regeneration, accelerated wound healing processes and excellent antioxidant and antibacterial activity. This review will be focused on the in vitro and in vivo therapeutic outcomes of wound dressings loaded with curcumin.

The Efficacy of Cholesterol-Based Carriers in Drug Delivery.

Several researchers have reported the use of cholesterol-based carriers in drug delivery. The presence of cholesterol in cell membranes and its wide distribution in the body has led to it being used in preparing carriers for the delivery of a variety of therapeutic agents such as anticancer, antimalarials and antivirals. These cholesterol-based carriers were designed as micelles, nanoparticles, copolymers, liposomes, etc. and their routes of administration include oral, intravenous and transdermal. The biocompatibility, good bioavailability and biological activity of cholesterol-based carriers make them potent prodrugs. Several in vitro and in vivo studies revealed cholesterol-based carriers potentials in delivering bioactive agents. In this manuscript, a critical review of the efficacy of cholesterol-based carriers is reported.