Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of −10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX

Formulation and optimization of ivermectin nanocrystals for enhanced topical delivery

The increasing resistance to antiparasitic drugs and limited availability of new agents highlight the need to improve the efficacy of existing treatments. Ivermectin (IVM) is commonly used for parasite treatment in humans and animals, however its efficacy is not optimal and the emergence of IVM-resistant parasites presents a challenge. In this context, the physico-chemical characteristics of IVM were modified by nanocrystallization to improve its equilibrium water-solubility and skin penetration, potentially improving its therapeutic effectiveness when applied topically. IVM-nanocrystals (IVM-NC) were prepared using microfluidization technique. The impact of several process/formulation variables on IVM-NC characteristics were studied using D-optimal statistical design. The optimized formulation was further lyophilized and evaluated using several in vitro and ex vivo tests. The optimal IVM-NC produced monodisperse particles with average diameter of 186 nm and polydispersity index of 0.4. In vitro results showed an impressive 730-fold increase in the equilibrium solubility and substantial 24-fold increase in dissolution rate. Ex vivo permeation study using pig's ear skin demonstrated 3-fold increase in dermal deposition of IVM-NC. Additionally, lyophilized IVM-NC was integrated into topical cream, and the resulting drug release profile was superior compared to that of the marketed product. Overall, IVM-NC presents a promising approach to improving the effectiveness of topically applied IVM in treating local parasitic infections

Ultrasound-Triggered Liposomes Encapsulating Quantum Dots as Safe Fluorescent Markers for Colorectal Cancer

Quantum dots (QDs) are a promising tool to detect and monitor tumors. However, their small size allows them to accumulate in large quantities inside the healthy cells (in addition to the tumor cells), which increases their toxicity. In this study, we synthesized stealth liposomes encapsulating hydrophilic graphene quantum dots and triggered their release with ultrasound with the goal of developing a safer and well-controlled modality to deliver fluorescent markers to tumors. Our results confirmed the successful encapsulation of the QDs inside the core of the liposomes and showed no effect on the size or stability of the prepared liposomes. Our results also showed that low-frequency ultrasound is an effective method to release QDs encapsulated inside the liposomes in a spatially and temporally controlled manner to ensure the effective delivery of QDs to tumors while reducing their systemic toxicity

Hyperthermia of Magnetically Soft-Soft Core-Shell Ferrite Nanoparticles

Magnetically soft-soft MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized through a seed-mediated method using the organometallic decomposition of metal acetyl acetonates. Two sets of core-shell nanoparticles (S1 and S2) of similar core sizes of 5.0 nm and different shell thicknesses (4.1 nm for S1 and 5.7 nm for S2) were obtained by changing the number of nucleating sites. Magnetic measurements were conducted on the nanoparticles at low and room temperatures to study the shell thickness and temperature dependence of the magnetic properties. Interestingly, both core-shell nanoparticles showed similar saturation magnetization, revealing the ineffective role of the shell thickness. In addition, the coercivity in both samples displayed similar temperature dependencies and magnitudes. Signatures of spin glass (SG) like behavior were observed from the field-cooled temperature-dependent magnetization measurements. It was suggested to be due to interface spin freezing. We observed a slight and non-monotonic temperature-dependent exchange bias in both samples with slightly higher values for S2. The effective magnetic anisotropy constant was calculated to be slightly larger in S2 than that in S1. The magnetothermal efficiency of the chitosan-coated nanoparticles was determined by measuring the specific absorption rate (SAR) under an alternating magnetic field (AMF) at 200–350 G field strengths and frequencies (495.25–167.30 kHz). The S2 nanoparticles displayed larger SAR values than the S1 nanoparticles at all field parameters. A maximum SAR value of 356.5 W/g was obtained for S2 at 495.25 kHz and 350 G for the 1 mg/mL nanoparticle concentration of ferrogel. We attributed this behavior to the larger interface SG regions in S2, which mediated the interaction between the core and shell and thus provided indirect exchange coupling between the core and shell phases. The SAR values of the core-shell nanoparticles roughly agreed with the predictions of the linear response theory. The concentration of the nanoparticles was found to affect heat conversion to a great extent. The in vitro treatment of the MDA-MB-231 human breast cancer cell line and HT-29 human colorectal cancer cell was conducted at selected frequencies and field strengths to evaluate the efficiency of the nanoparticles in killing cancer cells. The cellular cytotoxicity was estimated using flow cytometry and an MTT assay at 0 and 24 h after treatment with the AMF. The cells subjected to a 45 min treatment of the AMF (384.50 kHz and 350 G) showed a remarkable decrease in cell viability. The enhanced SAR values of the core-shell nanoparticles compared to the seeds with the most enhancement in S2 is an indication of the potential for tailoring nanoparticle structures and hence their magnetic properties for effective heat generation

Lauric acid-based thermosensitive delivery system for the treatment of head and neck squamous cell carcinoma

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.</p

Novel Anti-Acanthamoebic Activities of Irosustat and STX140 and Their Nanoformulations

Pathogenic Acanthamoeba produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosustat and STX140 alone, as well as their nanoformulations, against A. castellanii via amoebicidal, excystment, cytopathogenicity, and cytotoxicity assays. Nanoformulations of the compounds were successfully synthesized with high encapsulation efficiency of 94% and 82% for Irosustat and STX140, respectively. Nanoparticles formed were spherical in shape and had a unimodal narrow particle size distribution, mean of 145 and 244 nm with a polydispersity index of 0.3, and surface charge of −14 and −15 mV, respectively. Irosustat and STX140 exhibited a biphasic release profile with almost 100% drug released after 48 h. Notably, Irosustat significantly inhibited A. castellanii viability and amoebae-mediated cytopathogenicity and inhibited the phenotypic transformation of amoebae cysts into the trophozoite form, however their nanoformulations depicted limited effects against amoebae but exhibited minimal cytotoxicity when tested against human cells using lactate dehydrogenase release assays. Accordingly, both compounds have potential for further studies, with the hope of discovering novel anti-Acanthamoeba compounds, and potentially developing targeted therapy against infections of the central nervous system