Emerging materials and technologies for advancing bioresorbable surgical meshes.

Surgical meshes play a significant role in the treatment of various medical conditions, such as hernias, pelvic floor issues, guided bone regeneration, and wound healing. To date, commercial surgical meshes are typically made of non-absorbable synthetic polymers, notably polypropylene and polytetrafluoroethylene, which are associated with postoperative complications, such as infections. Biological meshes, based on native tissues, have been employed to overcome such complications, though mechanical strength has been a main disadvantage. The right balance in mechanical and biological performances has been achieved by the advent of bioresorbable meshes. Despite improvements, recurrence of clinical complications associated with surgical meshes raises significant concerns regarding the technical adequacy of current materials and designs, pointing to a crucial need for further development. To this end, current research focuses on the design of meshes capable of biomimicking native tissue and facilitating the healing process without post-operative complications. Researchers are actively investigating advanced bioresorbable materials, both synthetic polymers and natural biopolymers, while also exploring the performance of therapeutic agents, surface modification methods and advanced manufacturing technologies such as 4D printing. This review seeks to evaluate emerging biomaterials and technologies for enhancing the performance and clinical applicability of the next-generation surgical meshes. STATEMENT OF SIGNIFICANCE: In the ever-transforming landscape of regenerative medicine, the embracing of engineered bioabsorbable surgical meshes stands as a key milestone in addressing persistent challenges and complications associated with existing treatments. The urgency to move beyond conventional non-absorbable meshes, fraught with post-surgery complications, emphasises the necessity of using advanced biomaterials for engineered tissue regeneration. This review critically examines the growing field of absorbable surgical meshes, considering their potential to transform clinical practice. By strategically combining mechanical strength with bioresorbable characteristics, these innovative meshes hold the promise of mitigating complications and improving patient outcomes across diverse medical applications. As we navigate the complexities of modern medicine, this exploration of engineered absorbable meshes emerges as a promising approach, offering an overall perspective on biomaterials, technologies, and strategies adopted to redefine the future of surgical meshes.

Alendronate/lactoferrin-dual decorated lipid nanocarriers for bone-homing and active targeting of ivermectin and methyl dihydrojasmonate for leukemia.

Chronic myeloid leukemia is a hematological cancer, where disease relapse and drug resistance are caused by bone-hosted-residual leukemia cells. An innovative resolution is bone-homing and selective-active targeting of anticancer loaded-nanovectors. Herein, ivermectin (IVM) and methyl dihydrojasmonate (MDJ)-loaded nanostructured lipid carriers (IVM-NLC) were formulated then dually decorated by lactoferrin (Lf) and alendronate (Aln) to optimize (Aln/Lf/IVM-NLC) for active-targeting and bone-homing potential, respectively. Aln/Lf/IVM-NLC (1 mg) revealed nano-size (73.67 ± 0.06 nm), low-PDI (0.43 ± 0.06), sustained-release of IVM (62.75 % at 140-h) and MDJ (78.7 % at 48-h). Aln/Lf/IVM-NLC afforded substantial antileukemic-cytotoxicity on K562-cells (4.29-fold lower IC50), higher cellular uptake and nuclear fragmentation than IVM-NLC with acceptable cytocompatibility on oral-epithelial-cells (as normal cells). Aln/Lf/IVM-NLC effectively upregulated caspase-3 and BAX (4.53 and 15.9-fold higher than IVM-NLC, respectively). Bone homing studies verified higher hydroxyapatite affinity of Aln/Lf/IVM-NLC (1 mg; 22.88 ± 0.01 % at 3-h) and higher metaphyseal-binding (1.5-fold increase) than untargeted-NLC. Moreover, Aln/Lf/IVM-NLC-1 mg secured 1.35-fold higher in vivo bone localization than untargeted-NLC, with lower off-target distribution. Ex-vivo hemocompatibility and in-vivo biocompatibility of Aln/Lf/IVM-NLC (1 mg/mL) were established, with pronounced amelioration of hepatic and renal toxicity compared to higher Aln doses. The innovative Aln/Lf/IVM-NLC could serve as a promising nanovector for bone-homing, active-targeted leukemia therapy.

Codelivery of ivermectin and methyl dihydrojasmonate in nanostructured lipid carrier for synergistic antileukemia therapy.

Chronic myeloid leukemia is a life-threatening blood-cancer prevalent among children and adolescents. Research for innovative therapeutics combine drug-repurposing, phytotherapeutics and nanodrug-delivery. Ivermectin (Ivn) is a potent anthelmintic, repurposed for antileukemic-activity. However, Ivn exerts off-target toxicity. Methyl-dihydrojasmonate (MJ) is a phytochemical of known antileukemic potential. Herein, we developed for the first-time Ivn/MJ-coloaded nanostructured-lipid-carrier (Ivn@MJ-NLC) for leveraging the antileukemic-activity of the novel Ivn/MJ-combination while ameliorating possible adverse-effects. The developed Ivn@MJ-NLC possessed optimum-nanosize (97 ± 12.70 nm), PDI (0.33 ± 0.02), entrapment for Ivn (97.48 ± 1.48 %) and MJ (99.48 ± 0.57 %) and controlled-release of Ivn (83 % after 140 h) and MJ (80.98 ± 2.45 % after 48 h). In-vitro K562 studies verified Ivn@MJ-NLC prominent cytotoxicity (IC50 = 35.01 ± 2.23 µg/mL) with pronounced Ivn/MJ-synergism (combination-index = 0.59) at low-concentrations (5-10 µg/mL Ivn). Superior Ivn@MJ-NLC cytocompatibility was established on oral-epithelial-cells (OEC) with high OEC/K562 viability-ratio (1.49-1.85). The innovative Ivn@MJ-NLC enhanced K562-nuclear-fragmentation and afforded upregulation of caspase-3 and BAX (1.71 ± 0.07 and 1.45 ± 0.07-fold-increase, respectively) compared to control. Ex-vivo hemocompatibility and in-vivo-biocompatibility of parenteral-Ivn@MJ-NLC, compared to Ivn-solution, was verified via biochemical-blood analysis, histological and histomorphometric studies of liver and kidney tissues. Our findings highlight Ivn@MJ-NLC as an Ivn/MJ synergistic antileukemic platform, ameliorating possible adverse-effects.

Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK.

Neuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 48 mice, divided into 6 groups, eight mice each. Group 1 (normal control), Group 2 (blank nanoparticles-treated), Group 3 (LPS (untreated)), Groups 4, 5, and 6 received LPS, then Group 4 received free DX, Group 5 received DX-loaded calcium phosphate nanoparticles (DX@CaP), and Group 6 received DX-loaded calcium phosphate nanoparticles with a pectin coat (Pec/DX@CaP). At the end of the experimentation period, behavioral tests were carried out. Then, mice were sacrificed, and brain tissue was extracted and used for histological examination, and assessment of interleukin-6 positive cells in different brain areas, in addition to biochemical measurement of SOD activity, TLR-4, AMPK and Nrf2. LPS can induce prominent neuroinflammation. Treatment with (Pec/DX@CaP) can reverse most behavioral, histopathological, and biochemical changes caused by LPS. The findings of the current study suggest that (Pec/DX@CaP) exerts a significant reverse of LPS-induced neuroinflammation by enhancing SOD activity, AMPK, and Nrf2 expression, in addition to suppression of TLR-4.

Targeted delivery of genistein for pancreatic cancer treatment using hyaluronic-coated cubosomes bioactivated with frankincense oil.

Pancreatic cancer is an aggressive malignancy that remains a major cause of cancer-related deaths. Research for innovative anticancer therapeutic options is thus imperative. In this regard, phytotherapeutics offer great promise as efficient treatment modalities, especially leveraging nanodrug delivery. Herein, we innovatively coloaded the flavonoid genistein (Gen) and frankincense essential oil (FO) within cubosomes, which were then coated with the bioactive ligand hyaluronic acid (HA/Gen-FO-Cub) for active-targeting of pancreatic cancer. The novel HA/Gen-FO-Cub displayed optimum nanosize (198.2 ± 4.5 nm), PDI (0.27 ± 0.01), zeta-potential (-34.7 ± 1.2 mV), Gen entrapment (99.3 ± 0.01 %), and controlled Gen release (43.7 ± 1.2 % after 120 h). HA/Gen-FO-Cub exerted selective anticancer activity on pancreatic cancer cells (PANC-1; 8-fold drop in IC50), cellular uptake and anti-migratory effect compared to Gen solution. HA/Gen-FO-Cub revealed prominent cytocompatibility (100 ± 5.9 % viability of human dermal fibroblast). Moreover, HA/Gen-FO-Cub boosted the in vivo anticancer activity of Gen in an orthotopic cancer model, affording tumor growth suppression (2.5-fold drop) and downregulation of NFκB and VEGF (2.9- and 1.8-fold decrease, respectively), compared to Gen suspension. Antimetastatic efficacy and Bcl-2-downexpression was histologically confirmed. Our findings demonstrate the promising anticancer aptitude of HA/Gen-FO-Cub as an effective phytotherapeutic nanodelivery system for pancreatic cancer therapy.

Engineering tanshinone-loaded, levan-biofunctionalized polycaprolactone nanofibers for treatment of skin cancer.

Skin cancer is a challenging condition of the highest prevalence rate among other types of cancer. Thus, advancement of local therapeutic approaches for skin cancer is highly needed. Recently, the use of phytotherapeutics, like tanshinone IIA (Tan), as anticancer agents has become promising. In this work, we engineered Tan-loaded polycaprolactone nanofibers, biofunctionalized with levan and egg-lecithin (Tan@Lev/EL/PCL-NF) for local skin cancer therapy. Novel Tan@Lev/EL/PCL-NF were prepared using w/o-emulsion electrospinning, employing a 23-factorial design. Composite NF exhibited nanofiber diameter (365.56 ± 46.25 nm), favorable surface-hydrophilicity and tensile strength. Tan@Lev/EL/PCL-NF could achieve favorably controlled-release (100% in 5 days) and Tan skin-deposition (50%). In vitro anticancer studies verified prominent cytotoxicity of Tan@Lev/EL/PCL-NF on squamous-cell-carcinoma cell-line (SCC), with optimum cytocompatibility on fibroblasts. Tan@Lev/EL/PCL-NF exerted high apoptotic activity with evident nuclear fragmentation, G2/M-mitosis cell-cycle-arrest and antimigratory efficacy. In vivo antitumor activity was established in mice, confirming pronounced inhibition of tumor-growth (224.25 ± 46.89%) and relative tumor weight (1.25 ± 0.18%) for Tan@Lev/EL/PCL-NF compared to other groups. Tan@Lev/EL/PCL-NF afforded tumor-biomarker inhibition, upregulation of caspase-3 and knockdown of BAX and MKi67. Efficient anticancer potential was further confirmed by histomorphometric analysis. Our findings highlight the promising anticancer functionality of composite Tan@Lev/EL/PCL-NF, as efficient local skin cancer phytotherapy.

Bioinspired 3D-printed scaffold embedding DDAB-nano ZnO/nanofibrous microspheres for regenerative diabetic wound healing.

There is a constant demand for novel materials/biomedical devices to accelerate the healing of hard-to-heal wounds. Herein, an innovative 3D-printed bioinspired construct was developed as an antibacterial/regenerative scaffold for diabetic wound healing. Hyaluronic/chitosan (HA/CS) ink was used to fabricate a bilayer scaffold comprising a dense plain hydrogel layer topping an antibacterial/regenerative nanofibrous layer obtained by incorporating the hydrogel with polylactic acid nanofibrous microspheres (MS). These were embedded with nano ZnO (ZNP) or didecyldimethylammonium bromide (DDAB)-treated ZNP (D-ZNP) to generate the antibacterial/healing nano/micro hybrid biomaterials, Z-MS@scaffold and DZ-MS@scaffold. Plain and composite scaffolds incorporating blank MS (blank MS@scaffold) or MS-free ZNP@scaffold and D-ZNP@scaffold were used for comparison. 3D printed bilayer constructs with customizable porosity were obtained as verified by SEM. The DZ-MS@scaffold exhibited the largest total pore area as well as the highest water-uptake capacity andin vitroantibacterial activity. Treatment ofStaphylococcus aureus-infected full thickness diabetic wounds in rats indicated superiority of DZ-MS@scaffold as evidenced by multiple assessments. The scaffold afforded 95% wound-closure, infection suppression, effective regulation of healing-associated biomarkers as well as regeneration of skin structure in 14 d. On the other hand, healing of non-diabetic acute wounds was effectively accelerated by the simpler less porous Z-MS@scaffold. Information is provided for the first-time on the 3D printing of nanofibrous scaffolds using non-electrospun injectable bioactive nano/micro particulate constructs, an innovative ZNP-functionalized 3D-printed formulation and the distinct bioactivity of D-ZNP as a powerful antibacterial/wound healing promotor. In addition, findings underscored the crucial role of nanofibrous-MS carrier in enhancing the physicochemical, antibacterial, and wound regenerative properties of DDAB-nano ZnO. In conclusion, innovative 3D-printed DZ-MS@scaffold merging the MS-boosted multiple functionalities of ZNP and DDAB, the structural characteristics of nanofibrous MS in addition to those of the 3D-printed bilayer scaffold, provide a versatile bioactive material platform for diabetic wound healing and other biomedical applications.

Chondroitin/Lactoferrin-dual functionalized pterostilbene-solid lipid nanoparticles as targeted breast cancer therapy.

Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.

Atorvastatin liposomes in a 3D-printed polymer film: a repurposing approach for local treatment of oral candidiasis.

Oral candidiasis (OC) is an opportunistic fungal infection, common amongst the elderly and the immunocompromised. Unfortunately, the therapeutic efficacy of common antifungals is imperiled by the rise of antifungal drug resistance. An alternative promising therapeutic option possibly contributing to antifungal therapy is drug repurposing. Herein, we aimed to employ novel pharmaceutical drug delivery for enhancing the emerging antifungal potential of the hypocholesterolemic drug atorvastatin (ATV). ATV-propylene-glycol-liposomes (ATV/PG-Lip) were prepared then integrated in 3D-printed (3DP) mucoadhesive films comprising chitosan, polyvinyl-alcohol and hydroxypropyl methylcellulose, as an innovative blend, for the management of OC. ATV/PG-Lip demonstrated good colloidal properties of particle size (223.3 ± 2.1 nm), PDI (0.12 ± 0.001) and zeta potential (-18.2 ± 0.3 mV) with high entrapment efficiency (81.15 ± 1.88%) and sustained drug release. Also, ATV/PG-Lip showed acceptable three-month colloidal stability and in vitro cytocompatibility on human gingival fibroblasts. The developed 3DP-films exhibited controlled ATV release (79.4 ± 1.4% over 24 h), reasonable swelling and mucoadhesion (2388.4 ± 18.4 dyne/cm2). In vitro antifungal activity of ATV/PG-Lip was confirmed against fluconazole-resistant Candida albicans via minimum inhibitory concentration determination, time-dependent antifungal activity, agar diffusion and scanning electron microscopy. Further, ATV/PG-Lip@3DP-film exceeded ATV@3DP-film in amelioration of infection and associated inflammation in an in vivo oral candidiasis rabbit model. Accordingly, the results confirm the superiority of the fabricated ATV/PG-Lip@3DP-film for the management of oral candidiasis and tackling antifungal resistance.

Nano zinc oxide-functionalized nanofibrous microspheres: A bioactive hybrid platform with antimicrobial, regenerative and hemostatic activities.

Bioactive hybrid constructs are at the cutting edge of innovative biomaterials. PLA nanofibrous microspheres (NF-MS) were functionalized with zinc oxide nanoparticles (nZnO) and DDAB-modified nZnO (D-nZnO) for developing inorganic/nano-microparticulate hybrid constructs (nZnO@NF-MS and D-nZnO@NF-MS) merging antibacterial, regenerative, and haemostatic functionalities. The hybrids appeared as three-dimensional NF-MS frameworks made-up entirely of interconnecting nanofibers embedding nZnO or D-nZnO. Both systems achieved faster release of Zn2+ than their respective nanoparticles and D-nZnO@NF-MS exhibited significantly greater surface wettability than nZnO@NF-MS. Regarding bioactivity, D-nZnO@NF-MS displayed a significantly greater and fast-killing effect against Staphylococcus aureus. Both nZnO@NF-MS and D-nZnO@NF-MS showed controllable concentration-dependent cytotoxicity to human gingival fibroblasts (HGF) compared with pristine NF-MS. They were also more effective than pristine NF-MS in promoting migration of human gingival fibroblasts (HGF) in the in vitro wound healing assay. Although D-nZnO@NF-MS showed greater in vitro hemostatic activity than nZnO@NF-MS (blood-clotting index 22.82 ± 0.65% vs.54.67 ± 2.32%), both structures exhibited instant hemostasis (0 s) with no blood loss (0 mg) in the rat-tail cutting technique. By merging the multiple therapeutic bioactivities of D-nZnO and the 3D-structural properties of NF-MS, the innovative D-nZnO@NF-MS hybrid construct provides a versatile bioactive material platform for different biomedical applications.

3D printed bioinspired scaffolds integrating doxycycline nanoparticles: Customizable implants for in vivo osteoregeneration.

3D printing has revolutionized pharmaceutical research, with applications encompassing tissue regeneration and drug delivery. Adopting 3D printing for pharmaceutical drug delivery personalization via nanoparticle-reinforced hydrogel scaffolds promises great regenerative potential. Herein, we engineered novel core/shell, bio-inspired, drug-loaded polymeric hydrogel scaffolds for pharmaceutically personalized drug delivery and superior osteoregeneration. Scaffolds were developed using biopolymeric blends of gelatin, polyvinyl alcohol and hyaluronic acid and integrated with composite doxycycline/hydroxyapatite/polycaprolactone nanoparticles (DX/HAp/PCL) innovatively via 3D printing. The developed scaffolds were optimized for swelling pattern and in-vitro drug release through tailoring the biphasic microstructure and wet/dry state to attain various pharmaceutical personalization platforms. Freeze-dried scaffolds with nanoparticles reinforcing the core phase (DX/HAp/PCL-LCS-FD) demonstrated favorably controlled swelling, preserved structural integrity and controlled drug release over 28 days. DX/HAp/PCL-LCS-FD featured double-ranged pore size (90.4 ± 3.9 and 196.6 ± 38.8 µm for shell and core phases, respectively), interconnected porosity and superior mechanical stiffness (74.5 ± 6.8 kPa) for osteogenic functionality. Cell spreading analysis, computed tomography and histomorphometry in a rabbit tibial model confirmed osteoconduction, bioresorption, immune tolerance and bone regenerative potential of the original scaffolds, affording complete defect healing with bone tissue. Our findings suggest that the developed platforms promise prominent local drug delivery and bone regeneration.

Engineering 3D-printed core-shell hydrogel scaffolds reinforced with hybrid hydroxyapatite/polycaprolactone nanoparticles for in vivo bone regeneration.

The versatility of 3D printing has rendered it an indispensable tool for the fabrication of composite hydrogel scaffolds, offering bone biomimetic features through inorganic and biopolymeric components as promising platforms for osteoregeneration. In this work, extrusion-based 3D printing was employed for the realization of osteoconductive composite biopolymer-based hydrogel scaffolds reinforced with hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) for osteoregeneration. The printing technique was optimized for ink printability and viscosity and crosslinking parameters, where a biopolymeric blend of gelatin, polyvinyl alcohol and hyaluronic acid was developed as innovative plain polymeric ink (PPI). Scaffolds were fabricated by 3D printing adopting a biphasic core/shell geometry, where the core phase of the scaffolds was reinforced with HAp/PCL NPs; the scaffolds were then freeze-dried. Novel composite freeze-dried, loaded-core scaffolds, HAp/PCL NPs-LCS-FD exhibited controlled swelling and maintained structural integrity for 28 days. The developed HAp/PCL NPs-LCS-FD also demonstrated double-ranged pore size, interconnected porosity and efficient mechanical stiffness and strength, favorable for osteoconductive actions. Cell infiltration studies, computed tomography and histomorphometry demonstrated that HAp/PCL NPs-LCS-FD afforded osteoconduction, biodegradation, biocompatibility and bone healing in rabbit tibial model, acting as a template for new bone formation. Our findings suggest that HAp/PCL NPs-LCS-FD could offer prominent bone regeneration and could be involved in various bone defects.

Hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles for enhanced osteogenesis.

Hydroxyapatite nanoparticles (HApN) are largely employed as osteogenic inorganic material. Inorganic/polymeric hybrid nanostructures can provide versatile bioactivity for superior osteogenicity, particularly as nanoparticles. Herein, we present hybrid biomaterial-based hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) realized using simple preparation techniques to augment HApN osteogenicity. Using wet chemical precipitation, we optimized HApN crystalline properties utilizing a 23-factorial design. Optimized HApN exhibited typical Ca/P elemental ratio with high reaction yield. Surface area analysis revealed their mesoporous nature and high surface area. Hybrid HAp/PCL NPs prepared using direct emulsification-solvent evaporation maintained HApN crystallinity with no observed chemical interactions. To the best of our knowledge, we are the first to elaborate the biocompatibility and osteogenicity of nanoparticulate hybrid HAp/PCL. Hybrid HAp/PCL NPs outperformed HApN regarding mesenchymal cell proliferation and osteodifferentiation with reduction of possible cytotoxicity. Unlike HApN, hybrid HAp/PCL NPs presented moderate expression of early osteogenic markers, Runx-2 and osteopontin and significantly elevated expression of the late osteogenic marker, bone sialoprotein after 10-day culture. Our results indicate that hybrid bioactive HAp/PCL NPs could offer a more prominent osteogenic potential than plain HApN for bone regenerative applications as a standalone nanoplatform or as part of complex engineered systems.

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation.

Nanoparticles (NPs) have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs) to modulate the release and reduce ulcerogenicity of piroxicam (PX) after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2), having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours), was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, t max, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene(®) 20 mg capsules (P≤0.001). Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05) as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2) had a significant potential of offsetting deleterious side effects common in PX use.

Novel treatment strategies for brain tumors and metastases.

This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application.