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Abstract: Synthetic chemotherapeutics have played a crucial role in minimizing mostly palliative symptoms associated with cancer; however, they have also created other problems such as system toxicity due to a lack of specificity. This has led to the development of polymer-drug conjugates amongst other novel drug delivery systems. Most of the formulations designed using delivery systems consist of synthetic drugs and face issues such as drug resistance, which has already rendered drugs such as antibiotics ineffective. This is further exacerbated by toxicity due to the long-term use. Given these problems and the fact that conjugation of synthetic compounds to polymers has been relatively slow with no formulation on the market after a decade of extensive studies, the focus has shifted to using this platform with medicinal plant extracts to improve solubility, specificity and increase drug release of medicinal and herbal bioactives. In recent years, various plant extracts such as flavonoids, tannins and terpenoids have been studied extensively using this approach. The success of formulations developed using novel drug-delivery systems is highly dependent on the tumour microenvironment especially on the enhanced permeability and retention effect. As a result, the compromised lymphatic network and ‘leaky’ vasculature exhibited by tumour cells act as a guiding principle in the delivery of these formulations. This review focuses on the state of the polymer-drug conjugates and their exploration with natural compounds, the progress and difficulties thus far, and future directions concerning cancer treatment.

Phosphorus removal from effluents is vital to avoid eutrophication. The subject study presents the development and performance of poly(phenylenediamine) isometric adsorbents produced through oxidation using (NH4)2S2O8 and K2Cr2O7 oxidants. K2Cr2O7 synthesized polymers showed better adsorption capacities. The presence of Cr Lewis acid on the surface endorsed phosphate interaction through inner-sphere complex mechanism. The maximum adsorption capacities for K2Cr2O7 synthesized polymers were 143, 217 and 69.0 mg/L for poly(o-phenylenediamine), poly(m-phenylenediamine) and poly(p-phenylenediamine) adsorbents, respectively. The superior performance of poly(m-phenylenediamine) was associated with minimal symmetrical arrangement, hence it was more amorphous as indicated by XRD patterns. Kinetic model fitted pseudo-second-order and isotherm favoured Langmuir. Adsorption process was also controlled by pore diffusion and external mass transfer in the sorbent. Poly(m-phenylenediamine) displayed high affinity in the presence of competing anions and was amenable to recycling.

A series of 25 new benzothiazole–urea–quinoline hybrid compounds were synthesized successfully via a three-step synthetic sequence involving an amidation coupling reaction as a critical step. The structures of the synthesized compounds were confirmed by routine spectroscopic tools (1H and 13C NMR and IR) and by mass spectrometry (HRMS). In vitro evaluation of these hybrid compounds for their antitubercular inhibitory activity against the Mycobacterium tuberculosis H37Rv pMSp12::GPF bioreporter strain was undertaken. Of the 25 tested compounds, 17 exhibited promising anti-TB activities of less than 62.5 µM (MIC90). Specifically, 13 compounds (6b, 6g, 6i–j, 6l, 6o–p, 6r–t, and 6x–y) showed promising activity with MIC90 values in the range of 1–10 µM, while compound 6u, being the most active, exhibited sub-micromolar activity (0.968 µM) in the CAS assay. In addition, minimal cytotoxicity against the HepG2 cell line (cell viability above 75%) in 11 of the 17 compounds, at their respective MIC90 concentrations, was observed, with 6u exhibiting 100% cell viability. The hybridization of the quinoline, urea, and benzothiazole scaffolds demonstrated a synergistic relationship because the activities of resultant hybrids were vastly improved compared to the individual entities. In silico ADME predictions showed that the majority of these compounds have drug-like properties and are less likely to potentially cause cardiotoxicity (QPlogHERG > −5). The results obtained in this study indicate that the majority of the synthesized compounds could serve as valuable starting points for future optimizations as new antimycobacterial agents.

Chitosan has become an established platform biopolymer with applications in biomedical engineering, nanomedicine, and the development of new materials with improved solubility, antimicrobial activity, and low toxicity. In this study, a series of chitosan derivatives were synthesized by conjugating various perfluorocarbon chains to chitosan via Schiff base formation or nucleophilic substitution, followed by quaternization with glycidyl trimethylammonium chloride to confer non-pH-dependent permanent positive charges. Synthesized fluorinated N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride polymers were characterized and investigated for their antibacterial efficacies against multidrug-resistant bacteria including clinical isolates. The polymers showed activity against both Gram-positive and Gram-negative bacteria (MIC = 64-512 μg/mL) but with greater potency against the former. They displayed rapid bactericidal properties, based on the MBC/MIC ratio, which were further confirmed by the time-kill kinetic assays. Given the properties presented here, fluorinated quaternary chitosan derivatives can serve as great candidates to be investigated as environmentally more benign, nontherapeutic antimicrobial agents that could serve as alternatives to the heavy reliance on antibiotics, which are currently in a very precarious state due to increasing occurrence of drug resistance.

Applications of essential oils as chemotherapeutics are limited because these aromatic oils are generally volatile, insoluble in aqueous media and easily degraded to non-active constituents when subjected to thermal-oxidative processes. The particles from gas-saturated solution (PGSS) technology allows for non-destructive processing of volatile oils into micronized formulations under high pressure and moderate temperature using supercritical carbon dioxide (scCO2). In this study, essential oil from lime (Citrus aurantifolia) with proven antidiabetic activity was processed with polyethylene glycol (PEG) and lauric acid (LA) using scCO2 in a high pressure reactor for 2 h at 120 bar and 45 °C. The polymer-oil mixtures were co-precipitated and micronized through a 500 μm nozzle. PGSS processing of C. aurantifolia oil with PEG and LA yielded roughly spherical microparticles with sizes ∼ 2 μm. Inclusion of the LA and encapsulation of the limonene-rich oil into the PEG particles were confirmed using FTIR and GC/MS respectively. Melting point and heat of fusion of the PEG/LA microparticles were lower when compared with particles produced with PEG only, resulting in higher oil loading capacity and yield. The scCO2-assisted polymeric encapsulation of the volatile oil reduced rapid vaporization and incorporation of LA with the PEG-oil formulation extended the mean release time in simulated physiological solutions. Free radical scavenging and alpha-amylase inhibitory activities of the lime oil were also preserved following encapsulation in the PEG/LA microparticles. In summary, production of PEG/LA microparticles with high yield and loading capacity of bioactive lime essential oil was achieved using the scCO2 encapsulation technology.

The recent upsurge in the number and magnitude of outbreaks of infectious diseases in Nigeria has been managed effectively and efficiently by the Nigeria Centre for Disease Control (NCDC) in an increasingly epidemiology guided approach led by a skilled workforce within the one health collaborative agenda.1–4 The increasing number of the outbreaks of re-emerging infectious diseases could not have been unconnected to the effect of global warming with its resultant effect in the changing population activities and interaction with nature.5–7 Nigeria could not have effectively contained these emerging public health challenges had she not taken steps in developing her public health infrastructure, the laboratory capabilities and manpower development. Since 2008, the Nigeria Field Epidemiology Laboratory Training Program (NFELTP), a collaborative effort by NCDC, Federal Ministry of Health, Federal Ministry of Agriculture and Rural Development, African Field Epidemiology Network (AFENET) with financial and technical support from the US Centers for Disease Control and Prevention (CDC) has been building epidemiology capacity for disease prevention and control. Field epidemiology, the art and practice of epidemiology in the field, has been adopted as an effective tool and practice in preventing, detecting and controlling emerging public health threats and crisis. Field epidemiology provides the scientific evidence for public health actions.

Platinum-based drugs are potent anticancer drugs and are effective for the treatment of various cancers. However, they are limited pharmacologically due to toxic side effects, drug resistance and p...

The Medical Research Council (Self-Initiated Research) and National Research Foundation, South Africa.

Malaria is an acute disease that is caused by the protozoan Plasmodium parasites. Drug resistance is the major problem that is hindering the control of this disease. In order to overcome drug resistance to commonly used antimalarials, nanocarriers which are biocompatible, non-toxic, and are able to deliver drugs to the target site were designed. Polyaspartamide-drug conjugates containing antimalarials that inhibit dihydrofolate reductase were prepared and characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA), Scanning electron microscope (SEM), Energy-dispersive X-ray analysis (EDX), particle size analysis, as well as in vitro antiplasmodial analysis and drug release studies at physiological pH values. NMR and FTIR results confirmed the successful incorporation of the drugs onto the conjugates. SEM images of the conjugates showed predominant spherical and cluster of globular morphologies. In vitro release mechanisms of the drugs from the conjugates were slow and sustained. Conjugates containing 4-aminosalicylic acid and pyrimethamine were found to be the most active against the asexual stage of the parasite with an IC50 value of 332.37 ± 6.46 nM. Conjugate containing 4-aminoquinoline derivative, pyrimethamine and primaquine exhibited moderate antimalarial activity with an IC50 value of 4.71 ± 0.70 nM.

Water pollution due to industrial processes has necessitated and spurred robust research into the development of adsorbent materials for remediation. Polyphenylenediamines (PPD) have attracted significant attention because of their dual cationic and redox properties. They are able to reduce Cr(VI) to Cr(III) in solution. Interrogation of the chemical processes involved in the Cr(VI) adsorption on para-PPD was primarily by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy. It was confirmed that the underlying oxidation of the amino groups to imines during the reduction of Cr(VI) to Cr(III) was irreversible. This process occurred at both acidic and alkaline conditions. Reduction was accompanied by Cr(III) chelation on the adsorbent surface. Further, regeneration with dilute aqueous NaOH and HCl extended the polymer's adsorptive capacity beyond exhaustion of its redox potentials.

Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p &lt, 0.001, IC50 of 1.35 ± 0.11 µM) compared to BA (IC50 of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment.

Malaria is a serious infectious parasitic disease that is also one of the world’s deadliest. It has been treatable for centuries, but due to drug resistance, it continues to exert an enormous toll on human lives and economies. Although the current combination of powerful antimalarial drugs has been pivotal to reducing mortality, modern pharmacological technologies can further reduce the risk of resistance from the malaria parasite before total eradication is achieved. In this chapter, we describe various nanobiotechnology systems that have been developed for the delivery of pharmaceuticals for the treatment of diseases like cancer, HIV/AIDS, and leishmaniasis, but have only been cursorily investigated for malaria. We discuss them under two broad technology platforms: encapsulation and polymer conjugation.

Sugarcane bagasse is the major solid waste product of the sugarcane industry. As a plant-derived biomass, it is an attractive environmentally friendly alternative to petroleum-based materials. Being a non-food agriculture product, its use as a raw material is more widely accepted. Sugarcane bagasse is comprised mainly of cellulose, hemicellulose and lignin. The aim of this study was to develop a low-cost anion exchange adsorbent from sugarcane bagasse for the removal of phosphates in aqueous solution. The adsorbent was developed by crosslinking chitosan with cellulose that was extracted from sugarcane bagasse. To obtain cellulose for covalent linkage with chitosan, the bagasse was pretreated with dilute sodium hydroxide and sulphuric acid solutions followed by bleaching with hydrogen peroxide. After this process, the material was modified using chitosan functionalized with epichlorohydrin to obtain the modified bagasse (SCB-CS). SCB-CS was characterized using Fourier transform infrared spectroscopy (FTIR) analysis that indicated the successful reduction in the content of lignin and hemicellulose. The grafting of chitosan derivatives within the matrix of cellulose was confirmed by intense peaks at 1651 cm−1 and 1589 cm−1 observed on the modified SCB-CS. SCB-CS was evaluated for its ability to remove phosphates from synthetic waste water and 61.51% removal and an adsorption capacity of 52.33 mg/g, where the initial concentration was 28.36 mg/L at an adsorbent dosage of 0.1 g was achieved.

Betulinic acid (BA) is a naturally occurring plant pentacyclic triterpenoid with activity against cancer and infectious diseases like malaria and AIDS. Its pharmacological activity is limited by low aqueous solubility and bioavailability. Attempts have been made to improve the solubility of BA by conjugation to the water-soluble polymer polyethylene glycol (PEG) but with very limited physico-chemical characterizations. This work presents physico-chemical characterizations of a PEG-BA conjugate using 1H NMR spectroscopy, electron microscopy, DLS and XRD. The NMR data showed successful conjugation through the formation of an amide bond with a 5% drug loading although the appearance of some chemical shift signals were solvent-dependent. TEM images showed a spherical morphology of the conjugate with average diameter of 59.58±4.47 nm.

Phosphorus is a micronutrient but when it exists in abundance, it can have detrimental environmental impact. Bentonite (Bent) modified with Fe, Co and Ni salts were synthesized and evaluated for ad...

Antibiotic resistance is increasing at such an alarming rate that it is now one of the greatest global health challenges. Undesirable toxic side-effects of the drugs lead to high rates of non-completion of treatment regimens which in turn leads to the development of drug resistance. We report on the development of delivery systems that enable antibiotics to be toxic against bacterial cells while sparing human cells. The broad-spectrum fluoroquinolone antibiotic moxifloxacin (Mox) was successfully conjugated to poly(ethylene glycol) (PEG) which was further encapsulated into the hydrophobic poly(e-caprolactone) (PCL) nanoparticles (NPs) with high efficiency, average particle size of 241.8 ± 4 nm and negative zeta potential. Toxicity against erythrocytes and MDBK cell lines and drug release in human plasma were evaluated. Hemocompatibility and reduced cytotoxicity of the PEG–Mox and PCL(PEG–Mox) NPs were demonstrated in comparison to free Mox. Antimicrobial activity was assessed against drug sensitive and resistant: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The antibacterial activity of Mox was largely maintained after conjugation. Our data shows that the toxicity of Mox can be effectively attenuated while, in the case of PEG–Mox, retaining significant antibacterial activity. At the conditions employed in this study for antimicrobial activity the encapsulated conjugate (PCL(PEG–Mox) NPs) did not demonstrate, conclusively, significant antibacterial activity. These systems do, however, hold promise if further developed for improved treatment of bacterial infections.

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in the global north. South Africa, as a major emerging economy, has made extensive investments in nanotechnology and bioinformatics and has the expertise and resources in vaccine development and manufacturing. This has been built at a national level through decades of investment. In this perspective article, we provide a synopsis of the investments made in nanotechnology and highlight how these could support innovation, research, and development for vaccines for this disease. We also discuss the application of bioinformatics tools to support rapid and cost-effective vaccine development and make recommendations for future research and development in this area to support future health challenges.

The contamination of the water supply with high levels of heavy metals from various human and industrial activities continues to present a major environmental problem. Heavy metals such as hexavalent chromium (Cr(VI)) are of particular concern since they pose serious health and environmental risks. Many polymeric materials with remarkable anion adsorbing properties have been developed and reported in the literature. However, there is still need to reduce the cost and/or improve the performance of these materials for environmental remediation. We report here the synthesis, characterization and application of a poly(para-phenylenediamine) (poly- p PD) organoclay-based composite for removal of Cr(VI) complexes from wastewater. Adsorption capacity of the composite was evaluated at different sample pH, contact time, adsorbent dose and initial concentration. The poly- p PD-based organoclay adsorbent with p PD and poly- p PD-organoclay, respectively. Using XPS, it was proven that the adsorbent also reduces Cr(VI) to Cr (III). The prepared poly- p PD-organoclay showed reuse over seven times but still retaining 80% of the recovery for Cr(VI). The composite also performed excellently in batch application to real industrial wastewater containing high levels of Cr(VI) ions and competing anions such as nitrates and sulfates.

Eucalyptol is the natural cyclic ether which constitutes the bulk of terpenoids found in essential oils of Eucalyptus spp. and is used in aromatherapy for treatment of migraine, sinusitis, asthma and stress. It acts by inhibiting arachidonic acid metabolism and cytokine production. Chemical instability and volatility of eucalyptol restrict its therapeutic application and necessitate the need to develop an appropriate delivery system to achieve extended release and enhance its bioactivity. However, the synthesis method of the delivery system must be suitable to prevent loss or inactivation of the drug during processing. In this study, supercritical carbon dioxide (scCO2) was explored as an alternative solvent for encapsulation and co-precipitation of eucalyptol with polyethylene glycol (PEG) and/or polycaprolactone (PCL) using the particles from gas-saturated solution (PGSS) process. Polymers and eucalyptol were pre-mixed and then processed in a PGSS autoclave at 45 °C and 80 bar for 1 h. The mixture in scCO2 was micronized and characterized. The presence of eucalyptol in the precipitated particles was confirmed by infrared spectroscopy, gas chromatography and mass spectrometry. The weight ratios of PEG–PCL blends significantly influenced loading capacity and encapsulation efficiency with 77% of eucalyptol encapsulated in a 4 : 1 composite blend of PEG–PCL. The particle size distribution of the PGSS-micronized particles ranged from 30 to 260 μm. ScCO2 assisted microencapsulation in PEG and PCL reduced loss of the volatile drug during a two-hour vaporization study and addition of PCL extended the mean release time in simulated physiological fluids. Free radical scavenging and lipoxygenase inhibitory activities of eucalyptol formulated in the PGSS-micronized particles was sustained. Findings from this study showed that the scCO2-assisted micronization can be used for encapsulation of volatile drugs in polymeric microparticles without affecting bioactivity of the drug.

One of the advantages of dihydropyrimidinones (DHPMs) is the molecular diversity that could be achieved through their synthesis from a three-component reaction by varying the starting reaction materials. Differences in substituted functional groups could lead to varying reactivities and thermal stability amongst the analogues. In this study, two different classes of DHPMs were synthesized and the effects of the various substituents on the DHPM ring were investigated. The compounds were structurally characterized using single-crystal X-ray diffractometry, 1H, 13C, COSY, HSQC and HMBC NMR techniques, FT-IR and High Resolution Mass Spectrometry (HRMS). N1 methylation of the DHPM was found to increase the thermal stability of the series of DHPMs investigated, which is an added advantage in thermal reactions. The nature of the alkyl substituent of the ester group at position 5 of the DHPM was also found to affect the ease of the nucleophilic substitution reaction during the functionalization of the DHPMs. A complementary DFT study aided in understanding the above results as well as to compare the general stability of the range of compounds.

A library of new hydropyrimidinone/thione compounds was synthesized via the classical Biginelli reaction using hydrated cerium(III) chloride as the catalyst. The presence of a trifluoromethyl or methyl group in the diketone starting material has been established to selectively control the outcome of the Biginelli reaction where one of the two possible pyrimidinone/thione compounds is formed. The results showed that the electronic effects of substituents of the diketone directly affect the product formation. The synthesized compounds were fully characterized using 1H, 13C, and two dimensional NMR (2D NMR) spectroscopy, single crystal X-ray diffractometry, FT-IR, and ESI-HDMS techniques. We also report on the uncommon one-bond correlations which were observed in the HMBC spectra and the interesting long-range heteronuclear coupling of fluorine to hydrogen and carbon.

Malaria is one of the oldest infectious diseases that afflict humans and its history extends back for millennia. It was once prevalent throughout the globe but today it is mainly endemic to tropical regions like sub-Saharan Africa and South-east Asia. Ironically, treatment for malaria has existed for centuries yet it still exerts an enormous death toll. This contradiction is attributed in part to the rapid development of resistance by the malaria parasite to chemotherapeutic drugs. In turn, resistance has been fuelled by poor patient compliance to the relatively toxic antimalarial drugs. While drug toxicity and poor pharmacological potentials have been addressed or ameliorated with various nanomedicine drug delivery systems in diseases like cancer, no clinically significant success story has been reported for malaria. There have been several reviews on the application of nanomedicine technologies, especially drug encapsulation, to malaria treatment. Here we extend the scope of the collation of the nanomedicine research literature to polymer therapeutics technology. We first discuss the history of the disease and how a flurry of scientific breakthroughs in the latter part of the nineteenth century provided scientific understanding of the disease. This is followed by a review of the disease biology and the major antimalarial chemotherapy. The achievements of nanomedicine in cancer and other infectious diseases are discussed to draw parallels with malaria. A review of the current state of the research into malaria nanomedicines, both encapsulation and polymer therapeutics polymer-drug conjugation technologies, is covered and we conclude with a consideration of the opportunities and challenges offered by both technologies.

The objective of present study was to develop an optimized polymeric nanoparticle system for the antiretroviral drug tenofovir. A modified nanoprecipitation method was used to prepare Eudragit RS PO nanoparticles of the drug. The effect of amount of polymer, surfactant concentration, and sonication time on particle size, particle distribution, encapsulation efficiency (EE), and zeta potential were assessed and optimized utilizing a three-factor, three-level Box-Behnken Design (BBD) of experiment. Fifteen formulations of nanoparticles were prepared as per BBD and evaluated for particle size, polydispersity index (PDI), EE, and zeta potential. The results showed that the measured mean particle sizes were in the range of 233 to 499 nm, PDI ranged from 0.094 to 0.153, average zeta potential ranged from −19.9 to −45.8 mV, and EE ranged between 98 and 99%. The optimized formulation was characterized forin vitrodrug release and structural characterization. The mean particle size of this formulation was 233 nm with a PDI of 0.0107. It had a high EE of 98% and average zeta potential of −35 mV, an indication of particle stability. The FTIR showed some noncovalent interactions between the drug and polymer but a sustained release was observedin vitrofor up to 80 hours.

Modified chitosan was prepared by chemical derivatisation using caproyl and palmitoyl fatty acid chains. The performance of the materials on the removal of phosphates in aqueous solutions was evaluated through a series of batch adsorption experiments. The phosphate adsorption studies showed enhanced adsorption efficiencies for caproyl chitosan (63%) and for palmitoyl chitosan (71%) in aqueous solutions containing phosphate at a pH of 6.2. The pristine and modified chitosans showed increases in the removal efficiency at an optimal solution pH of 4. The adsorption kinetics studies performed on palmitoyl-chitosan indicated that a contact time of approximately 30 minutes is required to reach equilibrium at solution concentrations ranging from 10-20 mg/l. Co-existing anions such as nitrates and sulphates do affect the phosphate removal efficiency of modified chitosans in aqueous solutions. This study demonstrates that modified chitosans has the potential of being used as a rigid and degradable material for water treatment.

Most of the currently used antimalarial drugs suffer from drug resistance, poor bioavailability and biodegradability, drug toxicity and poor water solubility. To overcome some of the aforementioned limitations, combination therapy involving the combination of two or more antimalarials is currently used. Malaria is also treated by combining selected antibiotics with antimalarials resulting in good treatment outcomes. In this research, the aforementioned approach was employed by developing polymer-drug conjugates incorporated with antimalarials and antibiotics for a synergistic effect. The successful incorporation of antimalarials and antibiotics onto the polyaspartamide-based conjugates was confirmed by 1H NMR, FTIR and SEM. The XRD spectrums displayed the amorphous nature of the conjugates and indicated the absence of free drugs. The antiplasmodial evaluation of the conjugates further revealed their antimalarial activity against the asexual stage of the parasite with a % inhibition in the range of 35.6–99.9 at 1 μM, and 55.4–100.8 at 5 μM which was either comparable or better than the free drugs. The incorporation of the antibiotics together with the antimalarials into the polymer revealed a synergistic effect indicating that antibiotics act as a potentiating agent. However, more research is needed to confirm these findings.

Tuberculosis (TB) ranks the second leading cause of death from an infectious disease worldwide. However, treatment of TB is affected by poor patient compliance due to the requirement for daily drug administration, for lengthy periods of time, often with severe drug-induced side effects. Nanomedicines have the potential to improve treatment outcomes by providing therapies with reduced drug doses, administered less frequently, under shortened treatment durations.In this article, we present the pathophysiology of the disease, focusing on pulmonary TB and the characteristics of drugs used in treatment and discuss the application of nanomedicines within this scope. We also discuss new formulation approaches for TB nanomedicines and directions for future research.Nanomedicines have the potential to improve TB treatment outcomes. New approaches such as nanoparticle systems able to impact the immune response of macrophages and deliver drug intracellularly, as well as the use of polymer-drug conjugates for drug delivery, are likely to play an important role in TB nanomedicines in future. However, further research is required before TB nanomedicines can be translated to the clinic.

Cell wall mycolic acids (MA) from Mycobacterium tuberculosis (M.tb) are CD1b presented antigens that can be used to detect antibodies as surrogate markers of active TB, even in HIV coinfected patients. The use of the complex mixtures of natural MA is complicated by an apparent antibody cross-reactivity with cholesterol. Here firstly we report three recombinant monoclonal scFv antibody fragments in the chicken germ-line antibody repertoire, which demonstrate the possibilities for cross-reactivity: the first recognized both cholesterol and mycolic acids, the second mycolic acids but not cholesterol, and the third cholesterol but not mycolic acids. Secondly, MA structure is experimentally interrogated to try to understand the cross-reactivity. Unique synthetic mycolic acids representative of the three main functional classes show varying antigenicity against human TB patient sera, depending on the functional groups present and on their stereochemistry. Oxygenated (methoxy- and keto-) mycolic acid was found to be more antigenic than alpha-mycolic acids. Synthetic methoxy-mycolic acids were the most antigenic, one containing a trans-cyclopropane apparently being somewhat more antigenic than the natural mixture. Trans-cyclopropane-containing keto- and hydroxy-mycolic acids were also found to be the most antigenic among each of these classes. However, none of the individual synthetic mycolic acids significantly and reproducibly distinguished the pooled serum of TB positive patients from that of TB negative patients better than the natural mixture of MA. This argues against the potential to improve the specificity of serodiagnosis of TB with a defined single synthetic mycolic acid antigen from this set, although sensitivity may be facilitated by using a synthetic methoxy-mycolic acid.

The emergence of new pathogenic strains together with continuous rise of antimicrobial resistance and the death of new antibiotics in the clinical pipeline raise an urgent call for the development of potent antimicrobial agents. There has been growing interest in the use of new agents, such as antimicrobial polymers, as alternatives for therapy and disinfection. Cationic chitosan derivatives, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chlorides (HTCC), have been widely studied as potent antibacterial agents. However, their systemic structure-activity relationship (SAR), activity toward drug resistant bacteria and fungi, and mode of action are very rare. Herein, we investigated antibacterial efficacies of the HTCC polymer derivatives against multidrug resistant bacteria, including clinical isolates. The polymers were found to be active against a variety of bacterial pathogens (MIC = 32−128 μg/mL). Interestingly, these polymeric materials were active against Streptococcus Gram-positive bacteria, which are a predominant cause of hospital-acquired infections (HAIs).

Chitosan (CS) is a semi-synthetic polysaccharide derived from the most abundant naturally occurring polymer, chitin. It has found applications in fields as diverse as health, cosmetics, agriculture, environmental remediation etc. While biodegradability is important for non-toxic polymer-based material, stable and mechanically resilient chitosan is needed for harsh environmental applications. We synthesized a nano-chitosan derivative (LA-CS-Suc) with comparable thermal stability as the parent polymer. Synthesis involved chemically linking an organic acid to CS via carbodiimide chemistry. LA-CS-Suc was characterized by FT-IR, TGA, DSC and DLS. Cellular toxicity was also carried out. Successful conjugation was confirmed by FT-IR spectroscopy. Thermal stability was comparable to parent polymer. LA-CS-Suc had particle sizes ranging from 215 to 320 nm and they showed no cellular toxicity.

Patient serum antibodies to mycolic acids have the potential to be surrogate markers of active tuberculosis (TB) when they can be distinguished from the ubiquitously present cross-reactive antibodies to cholesterol. Mycolic acids are known to interact more strongly with antibodies present in the serum of patients with active TB than in patients with latent TB or no TB. Examples of single stereoisomers of mycolic acids with chain lengths corresponding to major homologues of those present in Mycobacterium tuberculosis have now been synthesised with a sulfur substituent on the terminal position of the α-chain; initial studies have established that one of these binds to a gold electrode surface, offering the potential to develop second generation sensors for diagnostic patient antibody detection.

A new method for the stereoselective synthesis of the (R,R)-β-hydroxy-α-alkyl fatty acid fragment of mycolic acids, via an asymmetric anti-aldol reaction is reported. The ‘mycolic acid motif’ fragment was prepared in three steps and >98% ee.

The publisher regrets that the author list of the above paper which appeared in Chemistry and Physics of Lipids, vol. 163, pp. 800–808 contained errors. The correct author list is published above. The publisher would like to apologise for any inconvenience this may have caused to the authors of this article and readers of the journal.