Antibiotic elution and mechanical property of TiO2 nanotubes functionalized PMMA-based bone cements.

To overcome the disadvantage of current antibiotic bone cements with low drug elution efficiency, the hollow nanostructured titanium-dioxide (TiO2) nanotubes (TNTs) were formulated with antibiotic loaded bone cement to create nano diffusion networks, enabling enhanced release of antibiotic. By incorporation of TNTs into Poly(methyl methacrylate) (PMMA) based bone cement, more than 50% of loaded antibiotic (such as gentamicin or vancomycin) could be released in two months. As comparison, only about 5% of total drug release was achieved in the absence of TNTs. The mechanical properties of PMMA-based bone cements were well preserved after incorporation of TNTs. Furthermore, the compression strength and bending modules of TNTs formulated antibiotic bone cements could be maintained after the drug release for 70 days or aging in PBS buffer for 3 months. The insoluble TNTs in bone cement is believed to support the mechanical properties after wet aging.

Application of transglycosylated stevia and hesperidin as drug carriers to enhance biopharmaceutical properties of poorly-soluble artemisinin.

Biopharmaceutical properties of poorly water-soluble antimalarial drug, Artemisinin (ART), were improved by formulating amorphous solid dispersions with transglycosylated food additives (Hsp-G and Stevia-G) via co-spray drying. Both the formulated ART/Hsp-G and ART/Stevia-G showed superior dissolution properties with a burst release of more than 95% of drug within 5 min, whereas untreated ART dissolved only 4% in 5min. The supersaturation solubility of the formulated ART was enhanced by 2-fold as compared with untreated counterpart. The storage stability tests indicated that these formulations chemically stable at room temperature and under low humidity (<18% RH) conditions. However, high humidity (75% RH) induced re-crystallization and caused changes in the physical appearance of the solid dispersions. In addition, both the food additives and ART formulated samples showed low cytotoxicity to Caco-2 cell line suggesting their good biocompatibility. Thus, the formation of solid dispersions of ART with transglycosylated food additives is a potentially safe and effective approach to enhance the bioavailability of poorly water-soluble ART.

Mechanical properties and antibiotic release characteristics of poly(methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.

The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements. Importantly, there are no significant changes in the compression strength and bending modulus up to 6 months of aging in PBS buffer solution. The preserved mechanical properties of MSN-functionalized bone cements is attributed to the unchanged microstructures of the cements, as more than 96% of MSNs remains in the bone cement matrix to support the cement structures after 6 months of aging. In addition, the MSN-functionalized bone cements are able to increase the drug release of gentamicin (GTMC) significantly as compared with commercially available antibiotic-loaded bone cements. It can be attributed to the loaded nano-sized MSNs with uniform pore channels which build up an effective nano-network path enable the diffusion and extended release of GTMC. The combination of excellent mechanical properties and sustainable drug delivery efficiency demonstrates the potential applicability of MSN-functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery infection.

Dissolution and physicochemical stability enhancement of artemisinin and mefloquine co-formulation via nano-confinement with mesoporous SBA-15.

The objective of this study is to enhance the dissolution rate, supersaturation and physicochemical stability of combination of two poorly water-soluble anti-malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM) and scanning electron microscope (SEM) clearly indicate the amorphization of the crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution enhancement with a burst release of more than 95% of drugs within 30min. In addition, the combination formulation exhibits a stable supersaturation enhancement by 2-fold higher than that of the untreated crystalline counterparts. ART/MQF/SBA-15 samples possess excellent physicochemical stability under 2 different moderate storage conditions for 6 months. The amorphization of ART and MFQ via nano-confinement using mesoporous SBA-15 is a potentially promising approach to enhance the solubility of poorly water-soluble anti-malarial drugs that co-formulated into a single dosage form.

Nanostructured material formulated acrylic bone cements with enhanced drug release.

To improve antibiotic properties, poly(methyl methacrylate) (PMMA)-based bone cements are formulated with antibiotic and nanostructured materials, such as hydroxyapatite (HAP) nanorods, carbon nanotubes (CNT) and mesoporous silica nanoparticles (MSN) as drug carriers. For nonporous HAP nanorods, the release of gentamicin (GTMC) is not obviously improved when the content of HAP is below 10%; while the high content of HAP shows detrimental to mechanical properties although the release of GTMC can be substantially increased. As a comparison, low content of hollow nanostructured CNT and MSN can enhance drug delivery efficiency. The presence of 5.3% of CNT in formulation can facilitate the release of more than 75% of GTMC in 80 days, however, its mechanical strength is seriously impaired. Among nanostructured drug carriers, antibiotic/MSN formulation can effectively improve drug delivery and exhibit well preserved mechanical properties. The hollow nanostructured materials are believed to build up nano-networks for antibiotic to diffuse from the bone cement matrix to surface and achieve sustained drug release. Based on MSN drug carrier in formulated bone cement, a binary delivery system is also investigated to release GTMC together with other antibiotics.

Enhanced dissolution and stability of artemisinin by nano-confinement in ordered mesoporous SBA-15 particles.

Dissolution of poorly water-soluble drug, Artemisinin (ART), was enhanced by encapsulating the drug particles inside pore channels of ordered mesoporous silica, SBA-15, via co-spray drying. The drug release profiles of ART were investigated by using flow-through cell (USP IV) and in vitro dissolution tester (USP II). The co-spray-dried ART/SBA-15 samples demonstrated significantly improved dissolution rates and supersaturation compared to the untreated ART. The low cytotoxicity effect of ART and SBA-15 on Caco-2 cells after 24 h incubation demonstrated the biocompatibility of ART/SBA-15. Finally, the storage stability of the samples was investigated for 6 months under five different storage conditions. Overall, the solid dispersions exhibited excellent physical stability; however, their chemical stability was affected by humidity regardless of storage temperatures. The formulation of solid dispersions of ART/SBA-15 is potentially safe and an effective approach to enhance the solubility of poorly water-soluble ART.

Applications of mesoporous materials as excipients for innovative drug delivery and formulation.

Due to uniquely ordered nanoporous structure and high surface area as well as large pore volume, mesoporous materials have exhibited excellent performance in both controlled drug delivery with sustained release profiles and formulation of poorly aqueoussoluble drugs with enhanced bioavailability. Compared with other bulk excipients, mesoporous materials could achieve a higher loading of active ingredients and a tunable drug release profile, as the high surface density of surface hydroxyl groups offered versatility to be functionalized. With drug molecules stored in nano sized channels, the pore openings could be modified using functional polymers or nano-valves performing as stimuli-responsive release devices and the drug release could be triggered by environmental changes or other external effects. In particular, mesoporous silica nanoparticles (MSN) have attracted much attention for application in functional target drug delivery to the cancer cell. The smart nano-vehicles for drug delivery have showed obvious improvements in the therapeutic efficacy for tumor suppression as compared with conventional sustained release systems, although further progress is still needed for eventual clinical applications. Alternatively, unmodified mesoporous silica also exhibited feasible application for direct formulation of poorly water-soluble drugs to enhance dissolution rate, solubility and thus increase the bioavailability after administration. In summary, mesoporous materials offer great versatility that can be used both for on-demand oral and local drug delivery, and scientists are making great efforts to design and fabricate innovative drug delivery systems based on mesoporous drug carriers.

Mesoporous silica nanoparticle-functionalized poly(methyl methacrylate)-based bone cement for effective antibiotics delivery.

Poly(methyl methacrylate)-based bone cements are functionalized with mesoporous silica nanoparticles (MSN) to enable a highly efficient and sustained release of antibiotics to reduce the risk of post-operative joint infection. To overcome the limited drug release of 5% for only 1 day with the current commercial-grade bone cements, a 8 wt% MSN-formulated bone cement is able to increase the drug release efficiency by 14-fold and sustain the release for up to 80 days. The loaded MSN is suggested to build up an effective network of rod-shaped silica particles with uniformly arranged nanoporous channels, which is responsible for the effective drug diffusion and extend time-release to the external surfaces. MSN has no detrimental effect on the critical weight-bearing bending modulus and compression strength of bone cement. In vitro assay test results show a much sustained antibacterial effect and low cytotoxicity of MSN demonstrating the potential applicability of MSN-formulated bone cement.

Physical state and dissolution of ibuprofen formulated by co-spray drying with mesoporous silica: effect of pore and particle size.

A model poorly aqueous-soluble drug, ibuprofen (IBU), was co-spray dried with mesoporous silica materials having different pore sizes and particle sizes for dissolution enhancement. Drug molecules were entrapped inside the mesoporous channels at a high drug loading of 50:50 (w/w). The pore sizes were found to affect the physical state and particle size of IBU in mesoporous structures, which influenced the dissolution profiles. When IBU was co-spray dried with MCM-41 and SBA-15 with pore size smaller than 10 nm, amorphous state of IBU was obtained due to nano space confinement. In contrast, nanocrystals were obtained when ibuprofen was co-spray dried with large pore SBA-15-LP with pore size above 20 nm. The physical state of ibuprofen played a key role in affecting the dissolution of IBU from the solid dispersion. IBU in the amorphous state exhibited a higher dissolution rate than nanocrystalline IBU, even though the larger pore size could facilitate diffusion from the host matrix. The particle size of mesoporous silica showed a less pronounced effect on the dissolution of IBU. Thus, the amorphous/nanocrystalline state of ibuprofen was the most important influence on drug dissolution followed by the diffusion kinetics, particle size of IBU and path length from host matrix to dissolution medium.

Stabilized amorphous state of ibuprofen by co-spray drying with mesoporous SBA-15 to enhance dissolution properties.

A novel formulation process via co-spray drying ibuprofen (IBU) with mesoporous SBA-15 submicron particles exhibited excellence in production of stable amorphous IBU with significantly enhanced dissolution rate. With drug loading of IBU/SBA-15 ratio being 50:50 (w/w) or below, most drug molecules were entrapped inside the straight mesoporous channels via the co-spray drying and the morphology of SBA-15 submicron particles remained unchanged. IBU confined inside the mesoporous structure was in the amorphous state shown by PXRD and DSC measurements. The amorphous state of IBU in the solid dispersion showed remarkable stability when subject to stress test condition of 40 degrees C/75% RH in open pans for 12 months. The uniform pore walls were believed to prevent the re-crystallization of the homogeneously dispersed drug molecules inside the mesoporous channels with confined nanospace. The dissolution rate of IBU from the co-spray-dried solid dispersion was significantly enhanced to achieve a rapid release. Even after the accelerated stability test, the rapid drug release property was well preserved.