The objective of this study was to evaluate the intradermal delivery of curcumin utilising poly(vinylalcohol) (PVA)-based microneedles loaded with curcumin nanosuspension (CU-NS). Nanoprecipitation was used to formulate the CU-NS which was then incorporated into PVA microneedles arrays consisting of 11 × 11 microneedles of conical shape, measuring 900 µm in height and with 300 µm base diameter. The nanosuspension particle size was 520 ± 40 nm, with a polydispersity of 0.27 ± 0.02 using sodium lauryl sulfate (SLS) as a stabiliser. In vitro dissolution studies in 10% w/v Tween 80 showed that the CU-NS dissolved significantly faster than unmodified curcumin powder, with 34% released from the CU-NS, compared to 16% from the curcumin powder after 48 h. The CU-NS-loaded microneedles (CU-MN) were able to withstand a compression force of 32 N for 30 s. Moreover, these microneedles were able to penetrate excised neonatal porcine skin to a depth of 500 µm, dissolved completely in the skin within 60 min. After CU-MN dissolution, the drug diffused from the application site and migrated through the skin layers down to 2300 µm, significantly more than observed with topical application of CU-NS. This suggest that the fabricated microneedles with the incorporated CU-NS could enhance the intradermal delivery of curcumin.

Prosthetic joint infections (PJIs) ensued from total joint replacement (TJR) pose a severe threat to patients that involve poor health outcomes, severe pain, death (in severe cases), and negative influence patients’ quality of life. Antibiotic-loaded bone cement (ALBC) is frequently used for the prevention and treatment of PJI. This work aims to study gentamicin release from carbon nanotubes (CNTs) incorporated in polymethyl methacrylate (PMMA) bone cement to prolong release over several weeks to provide prophylaxis from PJIs after surgery. Different CNT concentrations were tested with the presence of gentamicin as a powder or preloaded onto carboxyl functionalized CNTs. The different types of bone cement were tested for drug release, mechanical properties, water uptake, antimicrobial properties, and cytocompatibility with human osteoblast cells (MTT, LDH, alizarin red, and morphology). Results showed prolonged release of gentamicin from CNT-loaded bone cements over several weeks compared to gentamicin-containing bone cement. Additionally, the presence of CNT enhanced the percentage of gentamicin released without adversely affecting the nanocomposite mechanical and antimicrobial properties needed for performance. Cytotoxicity testing showed non-inferior performance of the CNT-containing bone cement to the equivalent powder containing cement. Therefore, the developed nanocomposites may serve as a novel PMMA bone cement to prevent PJIs.

Microneedles have been widely studied for many topical and transdermal therapeutics due to their ability to painlessly puncture the skin, thereby bypassing the stratum corneum, the main skin barrier. In this study, ciprofloxacin (CIP) was loaded into dissolving polymeric microneedles prepared by a two-layer centrifugation method as a potential treatment of skin infections such as cellulitis. The polymers used were polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Two formulations were investigated, namely CIP_MN1, composed of 10 mg ciprofloxacin incorporated into a polymer matrix of PVA and PVP with a weight ratio of (9:1), and CIP_MN2, composed of 10 mg ciprofloxacin incorporated into PVA polymer. CIP_MN1 and CIP_MN2 showed a mean microneedle height of 188 and 179 µm, respectively. Since Parafilm has been proven as a model to examine the perforation of microneedles in skin, it was used to evaluate the ability of microneedles to perforate the skin. CIP_MN1 showed almost complete perforation of Parafilm, 190 pores, compared to CIP_MN2 which created only 85 pores in Parafilm, and therefore CIP_MN1 was used for subsequent studies. Examining CIP_MN1 on agarose gel as an in vitro model of human skin showed that the formula was able to fully perforate the agarose gel. Moreover, this formula showed significantly greater antimicrobial activity (p < 0.0001) compared to a free gel of ciprofloxacin against Staphylococcus aureus in an agarose gel-based model. This was evidenced by a zone of inhibition of 29 mm for the microneedle formulation of ciprofloxacin (CIP_MN1) compared to 2 mm for the free gel of ciprofloxacin. Furthermore, the CIP_MN1 showed complete dissolution in human skin after 60 min from application. Finally, the skin deposition of CIP_MN1 was investigated in ex vivo excised human skin. CIP_MN1 showed significantly more deposition of ciprofloxacin in deeper skin layers compared to the free gel of ciprofloxacin, and the released ciprofloxacin from the microneedles tends to migrate to deeper layers with time. Collectively, these results suggest that CIP_MN1 can be a potential delivery system for the treatment of S. aureus skin infections.

Needle phobia remains a major drawback of conventional injectable medications, leading to avoidance and low adherence among a reasonable portion of patients. Despite this, there is a limited number of studies investigating needle phobia prevalence and symptoms. In this survey, we studied the knowledge and prevalence of needle phobia and its manifestations among 1182 adult Jordanians. Moreover, we assessed the feasibility of microneedles delivery systems as an alternative approach to conventional injectable methods. The results revealed that 28.5% of the participants identified themselves with needle phobia, with a notably higher prevalence among females compared to males (p-value < 0.001). The overall prevalence of needle phobia based on its measured manifestations was found to be 27.4%. The survey also found that 68% of the population were unfamiliar with the concept of microneedles despite the reasonable proportion of the population who were aware of the disadvantages of conventional injectable medications. Furthermore, the survey identified four significant predictors of needle phobia through hierarchical linear regression analysis. Gender, occupation, and negative past experiences with needle injections accounted for 3%, 1%, and 1% of the variance in needle phobia, respectively. In addition, the participants’ preference for microneedles over conventional injectables medications appeared as another significant predictor, contributing 5% of the variance. Overall, the model explained 10% of the variance in needle phobia. Collectively, this study provides an insight into needle phobia prevalence and manifestations in Jordan, while also exploring microneedles as an alternative drug delivery system for patients with needle phobia.

The distinctive physiological and physical properties of 3D cultures that mimic tumor microenvironments in vivo make them more suitable for assessing the efficacy of drugs and nanoparticles compared to 2D culture models. Therefore, this study aims to examine and contrast how liposomes interact with cell cultures in both 2D and 3D models. Hanging drop technique was used to generate 3D spheroids. Cellular toxicity of Doxorubicin and Doxil^®-liposomes was tested using an MTT assay. Cellular uptake of Doxil^®-liposomes was investigated in 3D and 2D cell culture models using flow cytometry and confocal microscopy. Finally, migration and invasion assays were used to investigate the Doxil^®-liposomes interaction with the two models 2D model and 3D model, respectively. Our findings show that cells were able to form spheroid structures when a specific cell ratio was maintained. Flow cytometry analysis revealed that 2D cells exhibited higher Doxil^®-liposome uptake than 3D cells. The data obtained from confocal and fluorescent microscopy supported the findings of the flow cytometry analysis. Furthermore, the MTT assay showed that Doxil^®-liposomes induced less metabolic-disruption compared to free Doxorubicin. Our results also demonstrated that Doxil^®-liposomes interacted more loosely with the 3D model than 2D cells, which was further confirmed by measurements of the total migration and invasion areas. Therefore, a 3D model replicating the in vivo conditions of tumor structure and extracellular matrix to assess the delivery of liposomal-nanoparticles to spheroids through a collagen matrix can be more informative and recapitulate the in vivo microenvironment than the 2D model.