Malignant gliomas are one of the deadliest forms of brain cancer and despite advancements in treatment, patient prognosis remains poor, with an average survival of 15 months. Treatment using conventional chemotherapy does not deliver the required drug dose to the tumour site, owing to insufficient blood brain barrier (BBB) penetration, especially by hydrophilic drugs. Additionally, low molecular weight drugs cannot achieve specific accumulation in cancerous tissues and are characterized by a short circulation half-life. Nanoparticles can be designed to cross the BBB and deliver their drugs within the brain, thus improving their effectiveness for treatment when compared to administration of the free drug. The efficacy of nanoparticles can be enhanced by surface PEGylation to allow more specificity towards tumour receptors. This review will provide an overview of the different therapeutic strategies for the treatment of malignant gliomas, risk factors entailing them as well as the latest developments for brain drug delivery. It will also address the potential of polymeric nanoparticles in the treatment of malignant gliomas, including the importance of their coating and functionalization on their ability to cross the BBB and the chemistry underlying that.

Background: The Box–Behnken design of experiments (BBD) is a statistical modelling technique that allows the determination of the significant factors in developing nanoparticles (NPs) using a limited number of runs. It also allows the prediction of the best levels of variables to obtain the desired characteristics (size, charge, and encapsulation efficiency) of the NPs. The aim of this study was to examine the effect of the independent variables (amount of polymer and drug, and surfactant concentration) and their interaction on the characteristics of the irinotecan hydrochloride (IRH)-loaded polycaprolactone (PCL) NPs and to determine the most optimum conditions for producing the desired NPs. Methods: The development of the NPs was carried out by a double emulsion solvent evaporation technique with yield enhancement. The NPs data were fitted in Minitab software to obtain the best fit model. Results: By using BBD, the most optimum conditions for producing the smallest size, highest magnitude of charge, and highest EE% of PCL NPs were predicted to be achieved by using 61.02 mg PCL, 9 mg IRH, and 4.82% PVA, which would yield 203.01 nm, −15.81 mV, and 82.35% EE. Conclusion: The analysis by BBD highlighted that the model was a good fit to the data, confirming the suitability of the design of the experiments.

Background: High-grade gliomas (HGGs) are highly malignant tumors with a poor survival rate. The inability of free drugs to cross the blood–brain barrier and their off-target accumulation result in dose-limiting side effects. This study aimed at enhancing the encapsulation efficiency (EE) of irinotecan hydrochloride trihydrate (IRH) within polycaprolactone (PCL) nanoparticles with optimized size and charge. Materials and Methods: IRH-loaded PCL nanoparticles were formulated using either the single emulsion (O/W, W/O and O/O) or double emulsion (W/O/O and W/O/W) solvent evaporation techniques. The nanoparticles were characterized for their size, zeta potential and EE, with the optimized nanoparticles being characterized for their drug release and cytotoxicity. Results: The amorphization of PCL and the addition of electrolytes to the aqueous phases of the W/O/W emulsion produced spherical nanoparticles with a mean diameter of 202.1 ± 2.0 nm and an EE of 65.0%. The IRH-loaded nanoparticles exhibited zero-order release and were cytotoxic against primary HGG cells. Conclusion: The amorphization of PCL improves its EE of hydrophilic drugs, while the addition of electrolytes to the aqueous phases of the W/O/W emulsion enhances their EE further. IRH-loaded PCL nanoparticles have the potential to deliver cytotoxic levels of IRH over a sustained period of time, enhancing the cell death of HGGs.

Background/Objectives: Despite the advantages of polycaprolactone (PCL) for drug delivery, it still lacks effective approaches to enhance its encapsulation of drugs. Blending PCL with less hydrophobic polymers can tailor physicochemical properties to overcome these limitations. This study, for the first time, integrates two beneficial approaches—polymer blending and Box–Behnken design (BBD) optimisation—to develop PCL-based blend nanoparticles (NPs) with enhanced encapsulation efficiency (EE), controlled particle size, and improved stability through surface charge modulation. Methods: Drug-loaded blend NPs were developed using a double emulsion method, with different polymer ratios. A BBD model was employed to investigate the influential factors that control the size, charge, and EE. Results: Blending PCL with a less hydrophobic polymer significantly improved EE, achieving 60.96% under optimal conditions. The BBD model successfully predicted conditions for obtaining NPs with optimum size, negative charge, and enhanced drug encapsulation. The drug amount was identified as the most influential factor for EE, while polymer amounts significantly impacted size and charge. Conclusions: Careful control of polymer ratios, drug amount, and surfactant levels was shown to significantly influence particle size, surface charge, and EE, with the balanced 50:50 PCL:PLGA blend achieving optimal physicochemical performance. Using the BBD, the study identified the predicted optimal formulation consisting of 162 mg polymer blend, 8.37 mg drug, and 8% surfactant, which is expected to yield NPs with a size of 283.06 nm, zeta potential of −31.54 mV, and EE of 70%. The application of BBD allowed systematic evaluation of the factors and their interactions, providing robust predictive models.

Background: Glioblastoma is an aggressive brain tumour with limited therapeutic options due to poor drug delivery, biological barriers, and systemic toxicity. SN38, the active metabolite of irinotecan hydrochloride (IRH), is a potent topoisomerase I inhibitor; however, its clinical application is hindered by poor chemical stability and dose-limiting toxicity. In this study, two complementary nanoparticle platforms were developed to improve camptothecin-based therapy in glioma-relevant cellular models. Methodology: SN38-loaded poly(ε-caprolactone) (PCL) nanoparticles (F22) were designed as a passive delivery system, while folate-functionalised polyethylene glycol–PCL (PEG–PCL) nanoparticles loaded with IRH (F23) were developed as an active targeting strategy. Physicochemical characterisation confirmed successful drug encapsulation and folate functionalisation. Both systems were evaluated in primary high-grade glioma (HGG) and endothelial cell models for cellular interaction, cytotoxicity, apoptosis, and inflammatory responses. Results: F22 induced concentration-dependent alterations in cellular granularity and significant cytotoxicity compared with controls, but also produced substantial endothelial toxicity. In contrast, F23 demonstrated altered cellular interaction behaviour, accompanied by improved tumour-associated selectivity and reduced endothelial cytotoxicity at lower concentrations. These observations may reflect enhanced cellular uptake associated with folate functionalisation. Confocal microscopy confirmed intracellular localisation of F23 in perinuclear regions. Importantly, F23 was associated with lower IL-6 secretion compared to free drug and non-targeted nanoparticles, suggesting reduced inflammatory activation and improved biocompatibility. Conclusion: Overall, passive PCL nanoparticles improved delivery efficiency of SN38, while folate-functionalised PEG–PCL systems provided a more favourable balance between efficacy, selectivity, and inflammatory compatibility. These findings highlight the importance of PEGylation and ligand-mediated surface engineering in glioma-directed nanomedicine.

One of the most common hospital-acquired infections is a wound infection. Bacterial infection of wounds is a critical problem, and healing of wound infections remains important concern for surgeons. The problem has been exaggerated because of the uncontrolled and quickly spreading resistance to the existing antimicrobial agents. To overcome bacterial resistance to antibiotics, a variety of alternatives have been suggested. Medicinal plants extracted through various methods, as well as their nano-formulations, have emerged as promising sources for novel antimicrobial agents. This study evaluates the antibacterial efficacy of Myristica fragrans (Nutmeg) seed extracts against multidrug-resistant pathogenic bacteria isolated from infected wounds. A total of 50 wound swab samples were collected from patients who were admitted to hospitals in Baghdad. Different biochemical tests were used to identify the isolated bacteria. An antibiotic susceptibility test was also done. M. fragrans seeds' ethanolic and aqueous crude extracts were prepared. The antibacterial activity of the extracts was investigated using the agar well diffusion method. Eight genera of bacterial agents were isolated and identified: Escherichia coli (58.3%), Acinetobacter baumannii (4.2%), Klebsiella pneumoniae (8.3%), Pseudomonas aeruginosa (20.8%), Enterobacter (8.3%), Staphylococcus aureus (80%), Staphylococcus epidermidis (11.5%), and Streptococcus sp. (7.7%). Antibiotic susceptibility test showed that the isolated bacteria were multidrug-resistant. The results revealed potential activity of M. fragrance seeds extracts against the isolated bacteria. Hot ethanolic extract showed antibacterial activity in all concentrations (2 mg/ml, 4 mg/ml, and 8 mg/ml). The highest inhibition zone was 17.00±2.000, 14.67±0.77, and 14.33±1.5 mm at a concentration of 8 mg/ml against A. baumannii, P. aeruginosa, and E. coli, respectively. Followed by K. pneumoniae, Enterobacter sp., and S. aureus, the zone of inhibition was 13.67±1.528 mm and 12.67±1155 mm, respectively. Hot aqueous extract also showed activity. The highest inhibition zone at a concentration of 8 mg/ml was against Enterobacter sp. (15.00±0.000 mm), followed by A. baumannii (14.67±0.577mm), K. pneumoniae (14.33±0.577 mm), P. aeruginosa (13.67±0.577 mm), E. coli (13.00±1.000 mm), and S. aureus (12.00±0.000mm). M. fragrans seed extracts showed antibacterial activity against both gram-positive and gram-negative multidrug-resistant pathogenic bacteria. Based on this work findings, M. fragrans extracts have a broad spectrum of antibacterial activity.