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Lung cancer is an uncontrolled and abnormal mass of growing cells with the highest mortality rate in the world. Progressive lung cancer shows a robust resistance to cancer therapy; today no acceptable therapeutic results are achieved with drugs. Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor and blocks the proliferation of downstream signals that prevent cancer cells from proliferating by inhibiting tyrosine phosphorylation of the epidermal growth factor receptor. It also increases survival rates in patients with progressive lung cancer. Gefitinib belongs to the BCS class II drugs and due to its low bioavailability; its clinical use has been severely restricted. In recent years, several research papers have been published on the use of nanoparticles to increase therapeutic efficacy and drug targeting in lung cancer. Furthermore, to enhance the therapeutic efficacy of gefitinib, nanoparticles have been extensively studied and several nanoparticles including polymers, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nano cells, albumin, and silica nanoparticles have been developed for the treatment of lung cancer. All of these nanocarriers have improved targeted gefitinib treatment of lung cancer and improved nanomedicines for lung cancer treatment. This article provides an overview of various nanotechnology-based carrier systems of gefitinib such as polymeric, lipidic, albumin, and silica nanoparticles for lung cancer therapy. It also discusses the targeted and responsive delivery of gefitinib along with a combination strategy for better therapeutic efficacy. We believe that this manuscript will bring important information for formulation scientists to overcome the biopharmaceutical challenges associated with gefitinib for better clinical outcomes.

Nanoparticles (NPs) serve as the contrasting agent in the computed tomography (CT) guided interventional devices and processes. The high contrast imaging of the patient is critical for accurate and early diagnosis, and thereafter the elimination of the abnormality. A high contrast CT scan helps in the diagnosis of blood clots, broken bones, carcinogenic tumors, infections, internal injuries and bleeding, and cardiovascular diseases. Thereafter it helps in the determination of the precise location of surgery, biopsy, and monitoring conditions after surgery. Besides iodine, today radiologists are interested in high atomic number NPs like gold, tantalum, bismuth, silver, etc. The advancement in NP-based CT-guided imaging for a specific target is highly desirable for effective intervention processes like drainage by catheter, needle insertion, etc. In computed tomography (CT) guided interventional devices and procedures, NPs are known to act as contrasting agents. High-contrast imaging of the patient is essential for an accurate and prompt diagnosis, followed by the treatment of the diseased site. Blood clots, shattered bones, cancerous tumors, infections, internal injuries and bleeding, and cardiovascular disorders can be easily diagnosed with the use of a CT scan with high contrast. In addition, it aids in determining the precise surgical site, conducting biopsies, and monitoring postoperative conditions. Iodine-based contrast agents have been the conventional choice, but lately, radiologists are also interested in NPs with a high atomic number, such as gold, tantalum, bismuth, silver, etc. This review talks about recent research on metallic NPs and the usage of their conjugates for CT imaging of tumors, special attention has been given to gold NPs.

Vaccines manufacture and enhancement for preventing infection and promoting quality of life are of great concern worldwide. For vaccine enhancement, to date, only limited adjuvants have been approved globally. One of them is alum, which presents several side effects and limitations. Related to vaccine administration, mucosal vaccination is a promising method since it can induce both mucosal and systemic immunity since oral mucosa is the most exposed site of the body to various microbes, pathogens, and environmental particles. Consequently, an escalated specific local immunity is required in which stability and integrity of an encapsulated antigen is expected to result in a stable mucosal vaccine to protect the antigens from degradative chemical reactions occurring in the oral cavity and act as immunomodulator. Carbonate apatite (CHA) has been one of the most innovative materials as a newly developed vaccine adjuvant since it can adequately enhance drug and protein stability and delivery in various disease therapies. However, CHA fabrication that meets the parameters for adjuvants and immunomodulators remains challenging. In the form of nanoparticles, CHA is reported to enable targeted delivery of dendritic cells (DC), enhance uptakes, cross presentation, and biodistribution, as well as immune responses. Therefore, the development of nano-CHA-encapsulated vaccine antigens is required to enhance oral mucosal vaccinations and their effectiveness to prevent diseases. This study focuses on factors and strategies that affect the designing, fabrication, and testing of CHA nanoparticles for oral mucosal vaccines, especially in the aspect of physicochemical, immunological, cellular, surface chemistry, and biofunctionalization of the nanoparticle.

Nowadays, antibiotic resistance poses a threat to public health worldwide. For this reason, non-traditional antibacterial products, such as silver nanoparticles (AgNPs), offer an opportunity to address this issue. Although AgNPs have been proven to be effective antimicrobial agents, we studied the antibacterial and antibiofilm effects of two novel AgNPs (AgNP-Aloe-1 and AgNP-Aloe-2) obtained by green synthesis, their cytotoxicity on a cell line derived from human keratinocytes, and their skin penetration. These AgNPs were obtained here for the first time from an Aloe maculata aqueous extract as a reducing and capping agent of Ag(I), with varying the initial silver concentrations (5 and 9 mM of AgNO₃ for AgNP-Aloe-1 and AgNP-Aloe-2, respectively). For all the assessments, these were compared with AgNPs obtained from a traditional chemical method employing hydroxylamine hydrochloride as a reducing agent and AgNO₃ (AgNP–NH₂OH·HCl). The AgNPs were characterized physicochemically by TEM, DLS, Zeta potential, UV–vis, fluorescence, and Raman spectroscopy. Additionally, the concentration of silver forming AgNPs and the reaction yield were determined. Both green-synthesized AgNPs showed an improvement in the inhibition of bacterial growth after 24 h of incubation for E. coli and S. aureus. AgNP-Aloe-1 presented a MIC 4 times lower for both bacteria compared to AgNP–NH₂OH·HCl, while AgNP-Aloe-2 presented a MIC 32 and 8 time lower for E. coli and S. aureus, respectively. Moreover, they produced a decrease in the biofilm biomass formation from P. aeruginosa at lower concentrations (6.25 μg/ml for AgNP-Aloe-1 and 1.56 μg/ml for AgNP-Aloe-2) than AgNP-NH₂OH·HCl which only showed a reduction of 30% at the maximum concentration tested. However, AgNP-Aloe-1 and AgNP-Aloe-2 were less efficient in eradicating pre-formed biofilm. Even though AgNP-Aloe-2 showed a lower reaction yield (31.7%) compared to AgNP-Aloe-1 (68.5%), they showed the best antibacterial activity. On the other hand, green-synthesized AgNPs were mainly retained in the stratum corneum of intact skin and reached lower concentrations in the viable epidermis than AgNP–NH₂OH·HCl. Moreover, AgNP-Aloe-1 and AgNP-Aloe-2 did not show cytotoxic effects on human keratinocytes at the antibacterial concentrations. Their improved performance and lower skin penetration could be attributed to their physicochemical properties, such as size (10–25 nm), charge (around −10 mV), and shape (tendency towards a spherical shape), but mainly to the presence of phytocompounds from the extract that remained attached to the AgNPs, as observed by Raman spectroscopy and UV–vis. For the reasons mentioned above, these novel AgNPs obtained by a more environmentally friendly method have the potential to be used as antibacterial agents, particularly for topical applications.

Long acting injectables (LAIs) using polymeric microspheres has been developed to increase patient compliance and reduce side effects. Among many methods for manufacturing polymeric microspheres, microfluidics technology is known to have excellent characteristics in that the produced polymeric microspheres have perfect spherical shape without surface defect and uniform size, and thus have outstanding efficacy without initial burst. However, the mass production of polymeric microspheres was not realized by the inherent limitation that microfluidics is suitable for small quantity manufacturing. Overcoming such limitations, we could show mass production of finasteride-loaded polymeric microspheres (PLGA 7525) for LAIs using our microfluidic manufacturing platform technology, IVL-DrugFluidic®. The microfluidic channels used in manufacturing were optimized through computational fluid dynamics (CFD) simulation to minimize the flow variation between microchannels and eliminated disturbance outside of microchannels by resistance channels. In addition, the solvent removal was improved by applying the baffle and foam breaker system. Therefore, microspheres were mass-produced in the GMP manufacturing environment in perfect spherical shape, smooth surface, and even size distribution. The encapsulation efficiency was almost 100% and the residual solvent was under the Standard of regulation. In the clinical trial using microspheres mass-produced by IVL-DrugFluidic®, we confirmed that the drug release was stably maintained for a month, the target period without initial burst. It was also confirmed that the drug release by dose of microspheres was uniformly proportional. In conclusion, the microsphere manufacturing platform technology, IVL-DrugFluidic® has been proven to be an appropriate system for mass production of polymeric microspheres optimized for LAIs through physicochemical characteristics and clinical trial.

A major driving factor for antimicrobial resistance which leads to treatment failure for microbial infections ascribed to C. albicans are the formation of biofilms. 3D printing is a rapidly evolving innovation which could revolutionize drug delivery based on its unprecedented opportunity for targeted and improved delivery. Herein, we designed and 3D printed microbots via two photon-polymerisation. Subsequently, characterisation was performed and the activity of microbots independently and in combination with allicin against C. albicans biofilms were investigated. The microbots independently did not affect C. albicans biofilm formation and adhesion nor was there any significant synergistic interaction between microbots and allicin combination. However, this study has pioneered the utilisation of microbots for microbiological applications such as in combination with an antimicrobial to target biofilms. These prototype microbots will act as a guide for the next generation of microbots which will be functionalised to disrupt biofilms magnetically, enhancing allicin delivery and activity.

Dunaliella salina, a green microalga, is among the main sources of bioactive β-carotene and zeaxanthin. Hence, it will be investigated for its antioxidant effectiveness in wound healing. The current study's objective is to create new chitosan nanoparticle loaded D. salina hexane: ethyl acetate extract (HEAE-CNPs) and methanol extract (ME-CNPs) to be used in accelerating wound healing in-vivo. Double emulsion technique was utilized to prepare the nanoparticles. The prepared HEAE-CNPs and ME-CNPs were examined for in-vitro release and in-vivo wound healing efficacy in Wistar rats. Results confirmed that D. salina hexane:ethyl acetate extract (HEAE) contains 19.167 mg/g β-carotene and 16.196 mg/g zeaxanthin, whereas the extract of methanol (ME) contains only small amounts of zeaxanthin 0.313 mg/g as quantified by HPLC. The D. salina loaded chitosan gel greatly slowed the total carotenoids release, according to the in-vitro release assays, in comparison with D. salina nanoparticle dispersion with a particle size in the nanorange. By decreasing factor alpha (TNF-α) of tumor necrosis and increasing vascular endothelial growth factor (VEGF) and collagen skin contents, both HEAE-CNPs and ME-CNPs demonstrated wound healing and regeneration.

Gold nanoparticles (AuNPs) are one of the most extensively studied nanomaterials and their distinct physicochemical properties make them suitable for versatile applications. Herein, we synthesized concave cube-shaped gold nanoparticles (CCAuNPs) and functionalized them with lactoferrin (Lf), a natural antimicrobial protein, through electrostatic interaction as well as weak covalent formation. The functionalization of CCAuNPs was confirmed through UV–Visible (i.e., bathochromic shift of the surface plasmon resonance peak by 7 nm), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectroscopy, and their surface zeta potential. The concave cusp of CCAuNPs was confirmed through atomic force microscopy (AFM). The Lf-functionalized CCAuNPs (Lf-CCAuNPs) exhibited superior antibacterial propensity against a series of bacteria when compared to that of CCAuNPs. However, they didn't demonstrate any antibacterial activity against Lactobacillus plantarum, one of the key beneficial gut bacteria. The lipid peroxidation (LPO) assay confirmed the oxidation of fatty acids in the bacterial membrane upon interaction with AuNPs, which made the bacterial membrane porous. The resultant membrane-impaired dead bacteria were visualized through CellTox™ Green assay as well as the Trypan Blue dye exclusion assay. Both the nanoparticles demonstrated excellent hemocompatibility as well as biocompatibility (both in vitro and in vivo) as confirmed by MTT assay and the levels of important functional biomarkers of liver (e.g., ALT, AST, and ALP) and kidney (e.g., creatinine, uric acid, and BUN) in the serum. Overall, Lf-CCAuNPs with excellent hemocompatibility, and biocompatibility can be deployed as potential antibacterial agents to tackle the menace of pathogenic bacteria.

Oral cancer has a poor survival rate despite comprehensive therapy. Current treatments result in acute side effects and fail to eliminate an aggressive group of cells overexpressing CD44. Such cells are capable of tumour initiating, self-renewal, invasion and metastasis, resulting in tumour relapse and resistance. This study aims to synthesise and characterise hyaluronic acid/chitosan-coated poly (lactic-co-glycolic acid) nanoparticles and assess their effectiveness in delivering Paclitaxel and Temozolomide to human tongue squamous cell carcinoma cell line that expresses high CD44 levels, in terms of cell cytotoxicity and apoptosis. This study also assesses the coordinated administration of Paclitaxel and Temozolomide and whether they exhibit significant synergistic cell inhibition effects with reduced introduced drug concentration if co-delivered simultaneously. Nanoparticles were synthesised with solvent evaporation method and characterised to assess their size, homogeneity, and zeta potential. Cell viability assay and real-time cell analysis were performed to examine the cell inhibitory effect of the drug-loaded nanoparticles. Cell apoptosis and cell cycle alteration were detected, and reactive oxygen species induction, mitochondrial membrane potential, and expressed genes associated with cell inhibition and death were evaluated. The synthesised nanoparticles had a nano-sized diameter of 260.40±11.54 nm, a positive zeta potential of +14.31±1.37 mV and a low polydispersity index value of 0.15±0.03. Paclitaxel, Temozolomide, and their combination have inhibited cell proliferation with half maximal inhibitory concentrations of 4 nM, 1000 μM and 2nM:300 μM, respectively. Compared to free drugs, the single-loaded and co-loaded drugs induced more cytotoxicity. Paclitaxel and Temozolomide showed a considerable synergistic inhibitory effect which was discovered to be more significant when the drugs were loaded in the nanoparticles. Drug-loaded nanoparticles were verified to induce higher cell apoptosis rates, cell proportion arrested at the S-phase of the cell cycle, reactive oxygen species generation, mitochondrial collapse and expression of genes associated with cellular inhibition and death than free drugs. These results demonstrate that the established nanoparticles could be a potential candidate for oral cancer therapy since they could deliver and improve the efficacy of single and dual drugs against oral cancer cells.