The five-year survival rate for women with ovarian cancer is very poor despite radical cytoreductive surgery and chemotherapy. Although most patients initially respond to platinum-based chemotherapy, the majority experience recurrence and ultimately develop chemoresistance, resulting in fatal outcomes. The current administration of cytotoxic compounds is hampered by dose-limiting severe adverse effects. There is an unmet clinical need for targeted drug delivery systems that transport chemotherapeutics selectively to tumor cells while minimizing off-target toxicity. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer. This review summarizes the progress in engineered nanoparticle research for drug delivery for ovarian cancer and discusses the potential use of GPCRs as molecular entry points to deliver anti-cancer compounds into ovarian cancer cells. A newly emerging treatment paradigm could be the personalized design of nanomedicines on a case-by-case basis.

Cannabidiol (CBD) has demonstrated therapeutic potential in treating epilepsy, multiple sclerosis, Alzheimer’s, Parkinson’s, and Crohn’s diseases. Despite its promising effects and analgesic, anti-inflammatory, and anxiolytic properties, oral CBD’s full potential is hindered by poor water solubility (0.7–10 μg/mL), low permeability, and chemical instability. This study aimed to enhance CBD’s dissolution, stability, and gastrointestinal (GI) permeability by forming a CBD–phospholipid complex (CBD-PLC). We hypothesised that CBD-PLC would enhance CBD’s hydrophilicity, thus improving GI barrier permeability. This study involved screening an optimal phospholipid (PL) using a Design of Experiments (DoE) approach to prepare CBD-PLC with nanosized droplets (194.3 nm). Dissolution studies revealed significantly enhanced release rates for CBD-PLC—44.7% at 2 h and 67.1% at 3 h—compared to 0% for pure CBD and 7.2% for a physical mixture (PM). Cellular uptake studies showed that at 30 µM, CBD-PLC exhibited 32.7% higher apparent permeability coefficients (P_app), nearly doubling at 40 µM compared to pure CBD. Cytotoxicity tests confirmed safety over 24 h, while 12-month stability tests demonstrated consistent performance under varied conditions. The results indicate that CBD-PLC improves CBD’s solubility, permeability, and stability, offering a promising strategy to address the limitations of oral CBD delivery systems.

PH-responsive polymeric micelles have been extensively studied for nanomedicine and take advantage of pH differentials in tissues for the delivery of large doses of cytotoxic drugs at specific target sites. Despite significant advances in this area, there is a lack of versatile and adaptable strategies to render micelles pH-responsive that could be widely applied to different payloads and applications. To address this deficiency, we introduce the concept of oligoelectrolyte-mediated, pH-triggered release of hydrophobic drugs from non-responsive polymeric micelles as a highly effective approach with broad scope. Herein, we investigate the influence of the oligoelectrolyte, oligo(2-vinyl pyridine) (OVP), loading and polymer molecular weight on the pH-sensitivity, drug loading/release and cytotoxicity of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) micelles using copolymers with either short or long hydrophobic blocks (PEG₄PCL₄ and PEG₁₀PCL₁₀, respectively). The micelles were characterized as a function of pH (7.4 to 3.5). Dynamic light scattering (DLS) revealed narrow particle size distributions (PSDs) for both the blank and OVP-loaded micelles at pH 7.4. While OVP encapsulation resulted in an increase in the hydrodynamic diameter (D_h) (cf. blank micelles), a decrease in the pH below 6.5 led to a decrease in the D_h consistent with the ionization and release of OVP and core collapse, which were further supported by proton nuclear magnetic resonance (¹H NMR) spectroscopy and UV-visible (UV-vis) spectrophotometry. The change in zeta potential (ζ) with pH for the OVP-loaded PEG₄PCL₄ and PEG₁₀PCL₁₀ micelles was different, suggesting that the location/distribution of OVP in the micelles is influenced by the polymer molecular weight. In general, co-encapsulation of drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX) or 7-ethyl-10-hydroxycamptothecin (SN38)) and OVP in the micelles proceeded efficiently with high encapsulation efficiency percentages (EE%). In vitro release studies revealed the rapid, pH-triggered release of drugs from OVP-loaded PEG₁₀PCL₁₀ micelles within hours, with higher OVP loadings providing faster and more complete release. In comparison, no triggered release was observed for the OVP-loaded PEG₄PCL₄ micelles, implying a strong molecular weight dependency. In metabolic assays the drug- and OVP-loaded PEG₁₀PCL₁₀ micelles were found to result in significant enhancement of the cytotoxicity compared to drug-loaded micelles (no OVP) or other controls. Importantly, micelles with low OVP loadings were found to be nearly as effective as those with high OVP loadings. These results provide key insights into the tunability of the oligoelectrolyte-mediated approach for the effective formulation of pH-responsive micelles and pH-triggered drug release.

Effective treatment of ovarian cancer is limited by late-stage detection and chemotherapy resistance. There is a clinical need for the discovery of novel molecular targets to enable the development of innovative theranostic approaches. We investigated the coagulation factor II receptor/protease-activated receptor 1 (F2R/PAR1) as a potential diagnostic/prognostic biomarker and therapeutic target for ovarian cancer treatment. Public RNA sequence and DNA microarray data were used to analyze F2R gene expression in ovarian cancers, with protein expression confirmed in tumor samples by flow cytometry, immunofluorescence, and immunohistochemistry (IHC). Functional assays were conducted to study effects of F2R suppression on tumor progression. Our analysis confirmed elevated F2R mRNA and protein expression in ovarian cancers, notably in patients with metastatic and chemotherapy-resistant disease. Kaplan–Meier survival analysis demonstrated an association between high F2R protein detection and reduced progression-free survival. F2R suppression in ovarian cancer cell lines reduced tumor cell motility, invasion, spheroid formation, and metabolism and enhanced carboplatin sensitivity. F2R is a compelling diagnostic/prognostic and therapeutic target that could be used to treat chemotherapy-resistant and metastatic disease. The evaluation of novel F2R targeting strategies, using antibody-conjugated drugs or F2R ligand-decorated drug carriers, could lead to the development of effective therapeutics for patients with ovarian cancer.

Background: Treatment of cutaneous wound infections is becoming a major clinical challenge due to the growing problem of antimicrobial resistance associated with existing wound treatments. Two prevalent pathogens in wound infections, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), continue to present a serious challenge, underscoring the critical need for new therapeutic alternatives. Methods: Novel alginate acid-buffered gels (ABF-1, ABF-2, and ABF-3) were developed using a combination of organic acids in various concentrations and buffered at a pH of 4.5. The acid-buffering capacity of the gels was evaluated against sodium hydroxide solution and simulated wound fluid (SWF) at different wound pHs, mimicking infected and non-infected wound environments. The in vitro antibacterial activity was assessed against resistant bacterial strains (Gram-positive and Gram-negative) using a microdilution method and wound biofilm assay. The rheological properties and cell viability of the gels were evaluated and the gel showing positive cell viability was further investigated for healing ability using an in vitro wound scratch assay. Results: The gels showed promising in vitro antibacterial activity against Staphylococcus epidermidis, S. aureus, and P. aeruginosa. Gels with higher acid concentrations (ABF-1 and ABF-2) were highly effective in reducing the bacterial load in chronic biofilms of S. aureus and P. aeruginosa, while the gel with a lower acid concentration (ABF-3) showed positive effects on the viability of skin cells (over 80% cells viable) and for promoting wound closure. All three gels demonstrated excellent acid-buffering capabilities. Conclusions: The acid-buffered gels demonstrate promising in vitro antibacterial effects, indicating their potential for enhancing wound healing.