Functionalized solid lipid nanoparticles combining docetaxel and erlotinib synergize the anticancer efficacy against triple-negative breast cancer.

The goal of the study was to fabricate folic acid functionalized docetaxel (DOC)/erlotinib (ERL)-loaded solid lipid nanoparticles (SLNs) to synergistically increase the anticancer activity against triple-negative breast cancer. DOC/ERL-SLNs were prepared by the high shear homogenization - ultrasound dispersion method (0.1 % w/v for DOC, and 0.3 %w/v for ERL) and optimized using Plackett Burman Design (PBD) followed by Box Behnken Design (BBD). The optimized SLNs demonstrated particle size < 200 nm, PDI < 0.35, and negative zeta potential with entrapment and loading efficiency of ∼80 and ∼4 %, respectively. The SLNs and folic acid functionalized SLNs (FA-SLNs) showed sustained release for both drugs, followed by Higuchi and Korsemeyer-Peppas drug release models, respectively. Further, the in vitro pH-stat lipolysis model demonstrated an approximately 3-fold increase in the bioaccessibility of drugs from SLNs compared to suspension. The TEM images revealed the spherical morphology of the SLNs. DOC/ERL loaded SLNs showed dose- and time-dependent cytotoxicity and exhibited a synergism at a molar ratio of 1:3 in TNBC with a combination index of 0.35 and 0.37, respectively. FA-DOC/ERL-SLNs showed enhanced anticancer activity as evidenced by MMP and ROS assay and further inhibited the colony-forming ability and the migration capacity of TNBC cells. Conclusively, the study has shown that SLNs are encouraging systems to improve the pharmaceutical attributes of poorly bioavailable drugs.

Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch.

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

Enhanced Therapeutic Efficacy Against Melanoma through Exosomal Delivery of Hesperidin.

Melanoma, characterized as the most aggressive and metastatic form of skin cancer, currently has limited treatment options, predominantly chemotherapy and radiation therapy. However, the drawbacks associated with parenterally administered chemotherapy underscore the urgent need for alternative compounds to combat melanoma effectively. Hesperidin (HES), a flavonoid present in various citrus fruits, exhibits promising anticancer activity. Nevertheless, the clinical utility of HES is hindered by challenges such as poor water solubility, a short half-life, and low oral bioavailability. In response to these limitations, we introduced a novel approach by formulating HES-loaded exosomes (Exo-HES). Isolation of exosomes was achieved through the ultracentrifugation method, and HES was efficiently loaded using the sonication method. The resulting formulations displayed a desirable particle size (∼106 nm) and exhibited a spherical morphology, as confirmed by scanning electron and atomic force microscopy. In vitro studies conducted on B16F10 cell lines demonstrated higher cytotoxicity of Exo-HES compared to free HES, supported by enhanced cellular uptake validated through coumarin-6-loaded exosomes. This superior cytotoxicity was further evidenced by DNA fragmentation, increased generation of free radicals (ROS), loss of mitochondrial membrane potential, and effective inhibition of colony formation. The antimetastatic properties of Exo-HES were confirmed through wound healing and transwell migration assays. Oral pharmacokinetics studies revealed a remarkable increase of approximately 2.5 times in oral bioavailability and half-life of HES when loaded into exosomes. Subsequent in vivo experiments utilizing a B16F10-induced melanoma model in Swiss mice established that Exo-HES exhibited superior anticancer activity compared to HES after oral administration. Importantly, no biochemical, hematological, or histological toxicities were observed in tumor-bearing mice treated with Exo-HES. These findings suggest that exosomes loaded with HES represent a promising nanocarrier strategy to enhance the therapeutic effectiveness of hesperidin in melanoma treatment.

Covid-19-Associated Mucormycosis: Histopathology of the Deadly Fungal Infection.

Introduction Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. Objective The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. Methods A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. Results The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% ( n = 26/38) of the patients had diabetes as a comorbidity, 84.2% ( n = 32/38) had a history of steroid intake, and 55.3% ( n = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% ( n = 29/38), periorbital fat/orbit 21.1% ( n = 8/38), maxillary sinus 15.8% ( n = 6/38) and ethmoid sinus 13.2% ( n = 5/38). In 76.3% ( n = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. Conclusion COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.

Corset suture: A novel technique of overlay appositional continuous sutures with air tamponade for management of large acute corneal hydrops.

Management of large acute corneal hydrops (ACH) has always been a challenge. Various medical and surgical management options have been used, such as topical steroids, cycloplegics, antiglaucoma medications, antibiotics, Descemet's membrane reposition, and pre-Descematic sutures, for the management of acute hydrops, but have shown limited benefit. We hereby describe a novel technique of appositional continuous overlay sutures along with air tamponade for surgical management of corneal edema following large ACH. In this technique, the epithelium is scraped to visualize the stromal cleft, and then corneal marking is done to locate the suture placement site. Next, a continuous overlay, 10-0 nylon suture is passed in a crisscross fashion, just like the laces of a corset. A small paracentesis is made to lower the intraocular pressure. Stromal fluid is milked out using two iris spatulas, simultaneous suture tension adjustment is done, and the knot is secured. Appropriate anterior chamber tamponade is achieved using air, paracentesis is hydrated, and a bandage contact lens is applied. We noted complete resolution of corneal edema within 2 weeks of the procedure, with significant improvement in visual acuity.

Unveiling the healing properties of 2,3-dehydrosilychristin: a potential silymarin-derived flavonolignan from Vitex negundo.

The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans - silybin, silychristin and silydianin - 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin (7) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin (7) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.

Advancements in microneedle fabrication techniques: artificial intelligence assisted 3D-printing technology.

Microneedles (MNs) are micron-scale needles that are a painless alternative to injections for delivering drugs through the skin. MNs find applications as biosensing devices and could serve as real-time diagnosis tools. There have been numerous fabrication techniques employed for producing quality MN-based systems, prominent among them is the three-dimensional (3D) printing. 3D printing enables the production of quality MNs of tuneable characteristics using a variety of materials. Further, the possible integration of artificial intelligence (AI) tools such as machine learning (ML) and deep learning (DL) with 3D printing makes it an indispensable tool for fabricating microneedles. Provided that these AI tools can be trained and act with minimal human intervention to control the quality of products produced, there is also a possibility of mass production of MNs using these tools in the future. This work reviews the specific role of AI in the 3D printing of MN-based devices discussing the use of AI in predicting drug release patterns, its role as a quality control tool, and in predicting the biomarker levels. Additionally, the autonomous 3D printing of microneedles using an integrated system of the internet of things (IoT) and machine learning (ML) is discussed in brief. Different categories of machine learning including supervised learning, semi-supervised learning, unsupervised learning, and reinforced learning have been discussed in brief. Lastly, a brief section is dedicated to the biosensing applications of MN-based devices.

Subconjunctival dexamethasone-assisted conjunctival autograft harvesting versus normal saline during pterygium surgery - A randomized clinical trial.

PURPOSE: To evaluate the effect of subconjunctival dexamethasone compared to normal saline on conjunctival autograft harvesting in patients undergoing pterygium surgery. METHODS: Fifty-two eyes of 52 patients who underwent pterygium excision combined with autologous conjunctival graft (CAG) using releasable suture were included in this prospective interventional study. The patients were randomized into two groups of 26 patients each. Group A consisted of patients in whom CAG was harvested using subconjunctival 0.5 ml of 0.4% dexamethasone sodium phosphate and in group B patients, normal saline was used. The patients were assessed for postoperative pain, foreign body sensation, and watering as the subjective signs of inflammation and conjunctival inflammation and lid edema as the objective signs of inflammation at 12 and 24 h postsurgery. RESULTS: The mean age of group A and B patients was 47.69 + 13.09 and 46.00 + 10.76 years, respectively. The male:female ratio was 1.6:1 in group A and 1.1:1 in group B. The mean surgical time in group A was 243.96 ± 52.13 s and in group B was 258.08 ± 43.99 s. Postoperative pain, foreign body sensation, and watering were significantly lower in group A patients than in group B patients at both 12 and 24 h postoperatively (group A: 4.65 ± 1.33, 4.88 ± 1.73, and 3.85 ± 1.43, respectively, at 12 h; 1.89 ± 1.03, 1.69 ± 1.09, and 1.69 ± 0.97, respectively, at 24 h and group B: 6.42 ± 0.95, 6.65 ± 0.98, and 6.27 ± 1.40, respectively, at 12 h; 3.27 ± 1.43, 3.12 ± 1.25, 2.58 ± 1.14, respectively, at 24 h) ( P < 0.001). Conjunctival inflammation was significantly lower in group A at 12 h ( P < 0.05) and 24 h ( P < 0.05) after surgery compared to group B. Lid edema failed to show any significant ( P = 0.17) difference with respect to severity in both the groups at 12 and 24 h ( P = 0.699). CONCLUSION: Subconjunctival dexamethasone decreased patient discomfort following pterygium surgery. The dexamethasone group had reduced conjunctival inflammatory signs without any notable complications.

Covid-19-Associated Mucormycosis: Histopathology of the Deadly Fungal Infection

Abstract Introduction Many patients suffered from rhino-orbital-cerebral mucormycosis during the coronavirus disease 2019 (COVID-19) pandemic in India. Diabetes is a known risk factor of COVID-19 infection and mucormycosis. Objective The present study was done to describe the clinical spectrum and histopathological findings of mucormycosis in COVID-19 patients and their outcomes. Methods A cross-sectional study was done over a period of two and half months. The biopsy samples or scrapings from sinonasal or periorbital tissue of 38 patients were analyzed. Hematoxylin & Eosin (H&E stain) slides were evaluated along with Grocott-Gomori methenamine-silver and Periodic acid-Schiff stains to highlight the fungal elements. Results The male to female ratio was 2.5:1, and the mean age of the subjects was 53 years old. A total of 68.4% (n = 26/38) of the patients had diabetes as a comorbidity, 84.2% (n = 32/38) had a history of steroid intake, and 55.3% (n = 21/38) were given supplemental oxygen during their treatment. The common presentations were nasal blockage, discharge, eye pain, headache, and altered mentation. The sites of biopsy were: nasal cavity 76.3% (n = 29/38), periorbital fat/orbit 21.1% (n = 8/38), maxillary sinus 15.8% (n = 6/38) and ethmoid sinus 13.2% (n = 5/38). In 76.3% (n = 29/38) cases, broad, irregular, nonseptate, and right-angle branching hyphae were seen on H&E-stained tissue sections. Conclusion COVID-19 led to various complications in individuals affected by it. Mucormycosis was one such lethal complication. An early diagnosis and prompt treatment is crucial to control the progression of the disease and improve outcomes.

Quantitative phase contrast X-ray tomography of aluminium metal matrix composite.

The quantitative assessment of micro-structure and load-induced damages in Al-SiC metal matrix composites (MMC) is important for its design optimization, performance evaluation and structure-property correlation. X-ray Phase contrast micro-tomography is potentially used for evaluation of its 3 dimensional micro-structure manifested in the form of voids, cracks, embedded particles, and load-induced damages. However, the contrast between Al matrix and SiC particles is insufficient for their clear morphological identification and quantitative assessment. In the present study, we have proposed and applied single image-based phase retrieval as a pre-processing step to micro-tomography reconstruction for improved assessment of micro-structure and cohesion-induced damages in Al-SiC MMC. The advantages of applying different phase retrieval techniques in the enhancement of image quality and morphological quantification of SiC particles, pores and cohesion damages are discussed. It is observed that the Paganin method offers the best improvement in contrast to noise ratio for the measurement of SiC particles embedded in the Al matrix.

Bacteriophage entrapped chitosan microgel for the treatment of biofilm-mediated polybacterial infection in burn wounds.

Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) bacteria are most commonly present in burn wound infections. Multidrug resistance (MDR) and biofilm formation make it difficult to treat these infections. Bacteriophages (BPs) are proven as an effective therapy against MDR as well as biofilm-associated wound infections. In the present work, a naturally inspired bacteriophage cocktail loaded chitosan microparticles-laden topical gel has been developed for the effective treatment of these infections. Bacteriophages against MDR S. aureus (BPSAФ1) and P. aeruginosa (BPPAФ1) were isolated and loaded separately and in combination into the chitosan microparticles (BPSAФ1-CHMPs, BPPAФ1-CHMPs, and MBP-CHMPs), which were later incorporated into the SEPINEO™ P 600 gel (BPSAФ1-CHMPs-gel, BPPAФ1-CHMPs-gel, and MBP-CHMPs-gel). BPs were characterized for their morphology, lytic activity, burst size, and hemocompatibility, and BPs belongs to Caudoviricetes class. Furthermore, BPSAФ1-CHMPs, BPPAФ1-CHMPs, and MBP-CHMPs had an average particle size of 1.19 ± 0.11, 1.42 ± 0.21, and 2.84 ± 0.28 µm, respectively, and expressed promising in vitro antibiofilm eradication potency. The ultrasound and photoacoustic imaging in infected burn wounds demonstrated improved wound healing reduced inflammation and increased oxygen saturation following treatment with BPs formulations. The obtained results suggested that the incorporation of the BPs in the MP-gel protected the BPs, sustained the BPs release, and improved the antibacterial activity.

Contribution of masticatory muscle pattern to craniofacial morphology in normal adults: A cross-sectional MRI study.

Purpose: The study aimed to determine the muscle pattern of medial pterygoid, lateral pterygoid, and masseter (length, cross-section, and angulation) in adult non-orthodontic patients and its effect on craniofacial structures. Methods: The study was conducted from January 14, 2019 to January 14, 2020. Ethical clearance of this study was obtained from the ethical committee Ethical Clearance was obtained from Faculty of Dental Sciences, IMS, BHU, Institutional Ethical Committee with Ref no. Dean/2019/EC/1824 dated 23.04.2019 of the university. The sample size was estimated using the G-power statistical program. Power analysis indicated a minimum sample size of 27. Inclusion and exclusion criteria were set. Consent was taken from participants. Seventy-seven subjects who were willing to participate and have given written consent were enrolled for the study. Participants were sent for lateral cephalometry (Dolphin Cephalometric software) Dolphin Imaging and management solution, for 6 angular and 11 linear measurements. Nineteen subjects did not turn up for the scan. Twenty-eight participants underwent MRI (magnetic resonance imaging) to evaluate muscle patterns (masseter, medial, and lateral pterygoid). The intra-class correlation coefficient (ICC), Kolmogorov-Smirnov (KS) test, descriptive statistics, and multiple regression analysis were computed. The P value was set as ≤0.001(highly statistically significant) and ≤0.05 (significant relation). Results: There was a highly statistically significant (p ≤ 0.001) association between masseter length to upper facial height (N-Ans) and ramal length (Cd-Go). Length of medial pterygoid was significantly related (p ≤ 0.05) with SNB and length of body of mandible (Pog-Go). The cross-section of this muscle showed significant relation with upper facial height (N-Ans) and ramal length (Cd-Go). The correlation of the length of lateral pterygoid with upper facial height (N-Ans) and maxillary length (A-Ptm) was highly significant. Conclusion: The muscle pattern has a significant correlation with maxillofacial morphology. The masseter muscle is the longest and thickest (cross-section) and is angulated vertically than the other two muscles (medial pterygoid and lateral pterygoid). Of the three muscles, the medial pterygoid influences more common craniofacial parameters suggestive of its symbiotic activity. Lateral pterygoid affects the maxillary length and facial height.

A Bacteriophage-Loaded Microparticle Laden Topical Gel for the Treatment of Multidrug-Resistant Biofilm-Mediated Burn Wound Infection.

Klebsiella pneumoniae is regarded as one of the most profound bacteria isolated from the debilitating injuries caused by burn wounds. In addition, the multidrug resistance (MDR) and biofilm formation make treating burn patients with clinically available antibiotics difficult. Bacteriophage therapy has been proven an effective alternative against biofilm-mediated wound infections caused by MDR bacterial strains. In the current study, the bacteriophage (BPKPФ1) against MDR Klebsiella pneumoniae was isolated and loaded into the chitosan microparticles (CHMPs), which was later incorporated into the Sepineo P 600 to convert into a gel (BPKPФ1-CHMP-gel). BPKPФ1 was characterized for lytic profile, morphological class, and burst size, which revealed that the BPKPФ1 belongs to the family Siphoviridae. Moreover, BPKPФ1 exhibited a narrow host range with 128 PFU/host cell of burst size. The BPKPФ1-loaded CHMPs showed an average particle size of  1.96 ± 0.51 µm, zeta potential 32.16 ± 0.41 mV, and entrapment efficiency in the range of 82.44 ± 1.31%. Further, the in vitro antibacterial and antibiofilm effectiveness of BPKPФ1-CHMPs-gel were examined. The in vivo potential of the BPKPФ1-CHMPs-gel was assessed using a rat model with MDR Klebsiella pneumoniae infected burn wound, which exhibited improved wound contraction (89.22 ± 0.48%) in 28 days with reduced inflammation, in comparison with different controls. Data in hand suggest the potential of bacteriophage therapy to be developed as personalized therapy in case of difficult-to-treat bacterial infections.

Impact of the Drug Loading Method on the Drug Distribution and Biological Efficacy of Exosomes.

Exosomes are biological nanovesicles that are intrinsically loaded with thousands of biomacromolecules and are principally responsible for cell-to-cell communication. Inspired by the natural payload, they have been extensively investigated as drug delivery vehicles; however, the drug distribution, whether into or onto exosomes, is still debatable. In the present work, we have tried to investigate it systemically by selecting 5-fluorouracil (5-FU) (hydrophilic) and paclitaxel (PAC) (hydrophobic), drugs with very different physicochemical characteristics, for the loading to the exosomes. Exosomes were obtained from bovine milk, and the drugs were loaded using three different methods: incubation, sonication, and triton x-100. The particle size was found to be approximately 100 nm in all the cases; however, the highest drug loading was found in the sonication method. Fluorescence spectrophotometer, EDX analysis, EDX mapping, XPS, and XRD analysis indicated the possible presence of more drugs over the surface in the case of the incubation method. Drugs loaded by the sonication method had more controlled release than simple incubation and triton x-100. The method of drug loading had an insignificant effect on the cytotoxicity while in line with our previous observation, the combination (PAC and 5-FU) exhibited synergism as evidenced by ROS assay, colony formation assay, and mitochondrial membrane potential assay.

A Bacteriophage Microgel Effectively Treats the Multidrug-Resistant Acinetobacter baumannii Bacterial Infections in Burn Wounds.

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is one of the major pathogens present in burn wound infections. Biofilm formation makes it further challenging to treat with clinically available antibiotics. In the current work, we isolated the A. baumannii-specific bacteriophages (BPABΦ1), loaded into the chitosan microparticles followed by dispersion in gel, and evaluated therapeutic efficacy against MDR A. baumannii clinical strains. Isolated BPABΦ1 were found to belong to the Corticoviridae family, with burst size 102.12 ± 2.65 PFUs per infected host cell. The BPABΦ1 loaded chitosan microparticles were evaluated for quality attributes viz. size, PDI, surface morphology, in vitro release, etc. The developed formulation exhibited excellent antibiofilm eradication potential in vitro and effective wound healing after topical application.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Melanoma is a deadly form of skin cancer that originates from melanocytes in the skin. Skin is a major barrier to drug delivery. Transferosome is a liquid nanoformulation that has the capacity for deeper skin penetration. The transferosome was prepared from standardized Piper longum fruit ethanolic extract (PLFEE) and loaded into gel to form a transgelosome for improved skin application and patient compliance. Compared with extract-loaded plain gel, the transgelosome showed good pharmaceutical properties with better activity in melanoma (B16F10)-bearing female C57BL/6 mice. The therapeutic activity of the standard anticancer drug dacarbazine was improved with the prepared PLFEE transgelosome.

Evaluation of surface-modified orthodontic wires by different concentration and dipping duration of titanium oxide (TiO2) nanoparticles.

OBJECTIVE: To evaluate in-vitro surface characteristics and frictional properties of orthodontic stainless steel and beta-titanium archwires after surface modification with different concentrations and coating time of titanium oxide (TiO2) nanoparticles by Sol-gel dip coating method. MATERIALS AND METHODS: The experiment was carried out with 4 different concentrations (1:2, 1:4, 1:6, and 1:8) and three different dipping durations (24 hours, 48 hours, and 72 hours) over ten main test groups of SS and TMA archwires with uncoated wires acting as control in both dry and wet conditions. Phase analysis and surface characterization of TiO2 was analyzed by X-ray Diffractometry, surface evaluation with the help of scanning electron microscopy (SEM), and frictional characteristics were evaluated. RESULTS: Among all the concentrations 1:6 ratio with 48 hours of dipping duration showed better surface characteristics. A statistically significant difference in frictional coefficient was observed in both SS and TMA wires than their respective controls (p = 0.001). Intragroup comparison among SS and TMA groups showed that groups with 1:6 ratio and 48 hours dipping duration had least frictional coefficient in both dry and wet conditions (p = 0.001). Intergroup comparison between SS and TMA showed that SS group had significantly reduced friction than TMA (p = 0.001) except in few groups. CONCLUSION: TiO2 nanoparticle with a concentration ratio of 1:6 and 48 hours dipping duration is recommended for surface modification of orthodontic archwires.

Quality by design-based development and optimization of fourth-generation ternary solid dispersion of standardized Piper longum extract for melanoma therapy.

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)-bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (Frel = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC.

Endorsement of TNBC Biomarkers in Precision Therapy by Nanotechnology.

Breast cancer is a heterogeneous disease which accounts globally for approximately 1 million new cases annually, wherein more than 200,000 of these cases turn out to be cases of triple-negative breast cancer (TNBC). TNBC is an aggressive and rare breast cancer subtype that accounts for 10-15% of all breast cancer cases. Chemotherapy remains the only therapy regimen against TNBC. However, the emergence of innate or acquired chemoresistance has hindered the chemotherapy used to treat TNBC. The data obtained from molecular technologies have recognized TNBC with various gene profiling and mutation settings that have helped establish and develop targeted therapies. New therapeutic strategies based on the targeted delivery of therapeutics have relied on the application of biomarkers derived from the molecular profiling of TNBC patients. Several biomarkers have been found that are targets for the precision therapy in TNBC, such as EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc. This review discusses the various candidate biomarkers identified in the treatment of TNBC along with the evidence supporting their use. It was established that nanoparticles had been considered a multifunctional system for delivering therapeutics to target sites with increased precision. Here, we also discuss the role of biomarkers in nanotechnology translation in TNBC therapy and management.

Recent advancements in nanotechnology-based bacteriophage delivery strategies against bacterial ocular infections.

Antibiotic resistance is growing as a critical challenge in a variety of disease conditions including ocular infections leading to disastrous effects on the human eyes. Staphylococcus aureus (S. aureus) mediated ocular infections are very common affecting different parts of the eye viz. vitreous chamber, conjunctiva, cornea, anterior and posterior chambers, tear duct, and eyelids. Blepharitis, dacryocystitis, conjunctivitis, keratitis, endophthalmitis, and orbital cellulitis are some of the commonly known ocular infections caused by S. aureus. Some of these infections are so fatal that they could cause bilateral blindness like panophthalmitis and orbital cellulitis, which is caused by methicillin-resistant S. aureus (MRSA) and vancomycin-resistance S. aureus (VRSA). The treatment of S. aureus infections with known antibiotics is becoming gradually difficult because of the development of resistance against multiple antibiotics. Apart from the different combinations and formulation strategies, bacteriophage therapy is growing as an effective alternative to treat such infections. Although the superiority of bacteriophage therapy is well established, yet physical factors (high temperatures, acidic pH, UV-rays, and ionic strength) and pharmaceutical barriers (poor stability, low in-vivo retention, controlled and targeted delivery, immune system neutralization, etc.) have the greatest influence on the viability of phage virions (also phage proteins). A variety of Nanotechnology based formulations such as polymeric nanoparticles, liposomes, dendrimers, nanoemulsions, and nanofibres have been recently reported to overcome the above-mentioned obstacles. In this review, we have compiled all these recent reports and discussed bacteriophage-based nanoformulations techniques for the successful treatment of ocular infections caused by multidrug-resistant S. aureus and other bacteria.