Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.

Handling and properties of nanoparticles strongly depend on processes that take place on their surface. Specific surface area and adsorption capacity strongly increase as the nanoparticle size decreases. A crucial factor is adsorption of water from ambient atmosphere. Considering the ever-growing number of hydroxyapatite nanoparticles applications, we decided to investigate how the size of nanoparticles and the changes in relative air humidity affect adsorption of water on their surface. Hydroxyapatite nanoparticles of two sizes: 10 and 40 nm, were tested. It was found that the nanoparticle size has a strong effect on the kinetics and efficiency of water adsorption. For the same value of water activity, the quantity of water adsorbed on the surface of 10 nm nano-hydroxyapatite was five times greater than that adsorbed on the 40 nm. Based on the adsorption isotherm fitting method, it was found that a multilayer physical adsorption mechanism was active. The number of adsorbed water layers at constant humidity strongly depends on particles size and reaches even 23 layers for the 10 nm particles. The amount of water adsorbed on these particles was surprisingly high, comparable to the amount of water absorbed by the commonly used moisture-sorbent silica gel.

Plant-derived natural medicines have been extensively studied for anti-inflammatory or antioxidant properties, but challenges to their clinical use include low bioavailability, poor solubility in water, and difficult-to-control release kinetics. Nanomedicine may offer innovative solutions that can enhance the therapeutic activity and control release kinetics of these agents, opening the way to translating them into the clinic. Two agents of particular interest are rutin (Ru), a flavonoid, and piperine (Pip), an alkaloid, which exhibit a range of pharmacological activities that include antioxidant and anti-inflammatory effects. In this work, nanoformulations were developed consisting of two metal–organic frameworks (MOFs) with surface modifications, Ti-MOF and Zr-MOF, each of them loaded with Ru and/or Pip. Both MOFs and nanoformulations were characterized and evaluated in vivo for anti-inflammatory and antioxidant effects. Loadings of ∼17 wt.% for a single pro-drug and ∼27 wt.% for dual loading were achieved. The release patterns for Ru and or Pip followed two stages: a zero-order for the first 12-hour stage, and a second stage of stable sustained release. At pH 7.4, the release patterns best fit to zero-order and Korsmeyer–Peppas kinetic models. The nanoformulations had enhanced anti-inflammatory and antioxidant effects than any of their elements singly, and those with Ru or Pip alone showed stronger effects than those with both agents. Results of assays using a paw edema model, leukocyte migration, and plasma antioxidant capacity were in agreement. Our preliminary findings indicate that nanoformulations with these agents exert better anti-inflammatory and antioxidant effects than the agents in their free form.

Synthetic calcium phosphates, e.g., hydroxyapatite (HAP) and tricalcium phosphate (TCP), are the most commonly used bone-graft materials due to their high chemical similarity to the natural hydroxyapatite—the inorganic component of bones. Calcium in the form of a free ion or bound complexes plays a key role in many biological functions, including bone regeneration. This paper explores the possibility of increasing the Ca²⁺-ion release from HAP nanoparticles (NPs) by reducing their size. Hydroxyapatite nanoparticles were obtained through microwave hydrothermal synthesis. Particles with a specific surface area ranging from 51 m²/g to 240 m²/g and with sizes of 39, 29, 19, 11, 10, and 9 nm were used in the experiment. The structure of the nanomaterial was also studied by means of helium pycnometry, X-ray diffraction (XRD), and transmission-electron microscopy (TEM). The calcium-ion release into phosphate-buffered saline (PBS) was studied. The highest release of Ca²⁺ ions, i.e., 18 mg/L, was observed in HAP with a specific surface area 240 m²/g and an average nanoparticle size of 9 nm. A significant increase in Ca²⁺-ion release was also observed with specific surface areas of 183 m²/g and above, and with nanoparticle sizes of 11 nm and below. No substantial size dependence was observed for the larger particle sizes.

Medical implant use is associated with a risk of infection caused by bacteria on their surface. Implants with a surface that has both bone growth-promoting properties and antibacterial properties are of interest in orthopedics. In the current study, we fabricated a bioactive coating of hydroxyapatite nanoparticles on polyether ether ketone (PEEK) using the sonocoating method. The sonocoating method creates a layer by immersing the object in a suspension of nanoparticles in water and applying a high-power ultrasound. We show that the simple layer fabrication method results in a well-adhering layer with a thickness of 219 nm to 764 nm. Dropping cefuroxime sodium salt (Cef) antibiotic on the coated substrate creates a layer with a drug release effect and antibacterial activity against Staphylococcus aureus. We achieved a concentration of up to 1 mg of drug per cm² of the coated substrate. In drug release tests, an initial burst was observed within 24 h, accompanied by a linear stable release effect. The drug-loaded implants exhibited sufficient activity against S. aureus for 24 and 168 h. Thus, the simple method we present here produces a biocompatible coating that can be soaked with antibiotics for antibacterial properties and can be used for a range of medical implants.

Guided tissue regeneration and guided bone regeneration membranes are some of the most common products used for bone regeneration in periodontal dentistry. The main disadvantage of commercially available membranes is their lack of bone cell stimulation and easy bacterial colonization. The aim of this work was to design and fabricate a new membrane construct composed of electrospun poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) fibers sonocoated with layers of nanoparticles with specific properties, i.e., hydroxyapatite and bimetallic nanocomposite of zinc oxide–silver. Thus, within this study, four different variants of biomaterials were evaluated, namely: poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) biomaterial, poly(D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite biomaterial, poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano zinc oxide–silver biomaterial, and poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver biomaterial. First, it was demonstrated that the wettability of biomaterials—a prerequisite property important for ensuring desired biological response—was highly increased after the sonocoating process. Moreover, it was indicated that biomaterials composed of poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) with or without a nano hydroxyapatite layer allowed proper osteoblast growth and proliferation, but did not have antibacterial properties. Addition of a nano zinc oxide–silver layer to the biomaterial inhibited growth of bacterial cells around the membrane, but at the same time induced very high cytotoxicity towards osteoblasts. Most importantly, enrichment of this biomaterial with a supplementary underlayer of nano hydroxyapatite allowed for the preservation of antibacterial properties and also a decrease in the cytotoxicity towards bone cells, associated with the presence of a nano zinc oxide–silver layer. Thus, the final structure of the composite poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver seems to be a promising construct for tissue engineering products, especially guided tissue regeneration/guided bone regeneration membranes. Nevertheless, additional research is needed in order to improve the developed construct, which will simultaneously protect the biomaterial from bacterial colonization and enhance the bone regeneration properties.