Assessment of radiation-induced sterility, longevity, and reproductive characteristics of the Aedes aegypti (Diptera: Culicidae) strain of Swat: A step towards the implementation of SIT in Pakistan.

BACKGROUND OBJECTIVES: Biological approaches for vector mosquito control such as sterile insect technique (SIT) requires sterilization of male mosquitoes through specific radiation doses for sterility induction in males. Under the SIT program, the males used must be compatible with the wild males in vigor, flight and selection of mate. Much of this potential is determined by the diet provided in the larval stages and optimizing the irradiation doses that cause complete sterility but have very minimal effect on the lives of irradiated males. The current study is designed to evaluate gamma radiation doses for inducing sterility in male Aedes aegypti mosquitoes with a genomic background from Pakistan (Swat district) and to assess the effects of radiation exposure on the competency of irradiated males and other life traits of irradiated mosquitoes. METHODS: Sterilization of 17-hour-old male pupae (groups of 50 pupa/cup in three replicates) of the Ae. aegypti Swat strain was conducted using radiation doses of 30, 60, 70, 90, and 105 gray (Gy) from (Co60) at the Nuclear Institute for Food and Agriculture (NIFA) in Peshawar, Pakistan. Post-irradiated pupae were released in adult cages. Virgin females of the same cohort were released (1:1) to mate with the irradiated males. Mortality, longevity, mating competitiveness of males, and female fecundity were recorded. RESULTS: An average of 71 eggs per female was recorded in control with 86% hatch rate. Individual females mated with a 60 Gy treated males produced 60 ± 0.6 eggs per female with 17% hatch rate, and those mated with 70 Gy males produced 42 ± 0.01 eggs with a nil hatch rate, whereas females mated with males treated with ≥70 Gy doses did not reproduce to next generation. Females in groups of 50 mated with 60, 70 Gy treated males (equal pairs), produced 369±1.3 and 98±0.01 eggs with 15% and zero hatch rate. Significant dose dependent reduction in longevity was observed for >30 Gy doses. The matting competence of irradiated males was about half that of un-irradiated males. INTERPRETATION CONCLUSION: Aedes aegypti with a Pakistani genomic background treated with a ≥70 Gy dose of gamma radiation induced complete sterility in males and provided the first- step foundation for SIT application in Pakistan. Further extensive studies are required to optimize the SIT techniques so that fully sterile males with very minor quality changes can be produced on large scales for field trials.

The effect of turmeric and black pepper powder incorporated in breakfast on postprandial glycemia, appetite, palatability, and gastrointestinal well-being in normal-weight adults.

Culinary herbs and spices are primarily known as flavor enhancers, research suggests that black pepper (Piper nigrum) and turmeric (Curcuma longa) have now been proven to prevent many non-communicable chronic diseases such as diabetes. Bioactive components of black pepper and turmeric ameliorate glucose metabolism and appetite regulation. The present research was designed to investigate the impact of turmeric and black pepper on blood glycemia, gastrointestinal well-being, appetite, and palatability. In a randomized crossover study, four iso-caloric experimental meals each having 50 g of available carbohydrates were subjected to healthy human participants (N = 20). Turmeric and black pepper were incorporated in the breakfast meal, 1 g black pepper (BP), 1 g turmeric (TR), and combination of the (BP + TR) was added in the breakfast. Standard questionnaires were used to evaluate palatability, subjective appetite, and gastrointestinal well-being. Blood glycemia, subjective gastrointestinal well-being, and appetite were measured at 0, 30, 60, 120, and 180 min. Experimental meals BP and BP + TR resulted in lower blood glycemia (p < .05) significantly compared to control meal. A decrease in perceived eating ability and hunger, and an increase in satiety after BP + TR and BP meal was observed. No significant changes were observed after consuming test meals on gastrointestinal well-being. Compared to control and BP + TR meals, BP and TR meals had considerably lower palatability. Results showed that compared to the control intake of starchy meals supplemented with black pepper and turmeric reduced postprandial glycemia, hunger, and perceived eating ability without affecting gastrointestinal well-being.

Formulation and Preparation of Losartan-Potassium-Loaded Controlled-Release Matrices Using Ethocel Grade 10 to Establish a Correlation between In Vitro and In Vivo Results.

In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 µg/mL), AUCo (5931.10 ± 1.232 µg·h/mL), AUCo-inf (7348.46 ± 0.234 µg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes.

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Nitazoxanide and quercetin co-loaded nanotransfersomal gel for topical treatment of cutaneous leishmaniasis with macrophage targeting and enhanced anti-leishmanial effect.

Purpose: Anti-leishmanial medications administered by oral and parenteral routes are less effective for treatment of cutaneous leishmaniasis (CL) and cause toxicity, hence targeted drug delivery is an efficient way to improve drug availability for CL with reduced toxicity. This study aimed to develop, characterize and evaluate nitazoxanide and quercetin co-loaded nanotransfersomal gel (NTZ-QUR-NTG) for the treatment of CL. Methods: NTZ-QUR-NT were prepared by thin film hydration method and were statistically optimized using Box-Behnken design. To ease the topical delivery and enhance the retention time, the NTZ-QUR-NT were dispersed in 2 % chitosan gel. Moreover, in-vitro drug release, ex-vivo permeation, macrophage uptake, cytotoxicity and anti-leishmanial assays were performed. Results: The optimized formulation indicated mean particle size 210 nm, poly dispersity index (PDI) 0.16, zeta potential (ZP) -15.1 mV and entrapment efficiency (EE) of NTZ and QUR was 88 % and 85 %, respectively. NTZ-QUR-NT and NTZ-QUR-NTG showed sustained release of the incorporated drugs as compared to the drug dispersions. Skin permeation of NTZ and QUR in NTZ-QUR-NTG was 4 times higher in comparison to the plain gels. The NTZ-QUR-NT cell internalization was almost 10-folds higher than NTZ-QUR dispersion. The cytotoxicity potential (CC50) of NTZ-QUR-NT (71.95 ± 3.32 µg/mL) was reduced as compared to NTZ-QUR dispersion (49.77 ± 2.15 µg/mL. A synergistic interaction was found between NTZ and QUR. Moreover, in-vitro anti-leishmanial assay presented a lower IC50 value of NTZ-QUR-NT as compared to NTZ-QUR dispersion. Additionally, a significantly reduced lesion size was observed in NTZ-QUR-NTG treated BALB/c mice, indicating its antileishmanial potential. Conclusion: It can be concluded that nanotransfersomal gel has the capability to retain and permeate the incorporated drugs through stratum corneum and induce synergetic anti-leishmanial effect of NTZ and QUR against cutaneous leishmaniasis.

Metformin HCl-loaded transethosomal gel; development, characterization, and antidiabetic potential evaluation in the diabetes-induced rat model.

Herein we designed, optimized, and characterized the Metformin Hydrochloride Transethosomes (MTF-TES) and incorporate them into Chitosan gel to develop Metformin Hydrochloride loaded Transethosomal gel (MTF-TES gel) that provides a sustained release, improved transdermal flux and improved antidiabetic response of MTF. Design Expert® software (Ver. 12, Stat-Ease, USA) was applied for the statistical optimization of MTF-TES. The formulation with Mean Particle Size Distribution (MPSD) of 165.4 ± 2.3 nm, Zeta Potential (ZP) of -21.2 ± 1.9 mV, Polydispersity Index (PDI) of 0.169 ± 0.033, and MTF percent Entrapment Efficiency (%EE) of 89.76 ± 4.12 was considered to be optimized. To check the chemical incompatibility among the MTF and other formulation components, Fourier Transform Infrared (FTIR) spectroscopy was performed and demonstrated with no chemical interaction. Surface morphology, uniformity, and segregation were evaluated through Transmission Electron Microscopy (TEM). It was revealed that the nanoparticles were spherical and round in form with intact borders. The fabricated MTF-TES has shown sustained release followed by a more pronounced effect in MTF-TES gel as compared to the plain MTF solution (MTFS) at a pH of 7.4. The MTF-TES has shown enhanced permeation followed by MTF-TES gel as compared to the MTFS at a pH of 7.4. In vivo antidiabetic assay was performed and results have shown improved antidiabetic potential of the MTF-TES gel, in contrast to MTF-gel. Conclusively, MTF-TES is a promising anti-diabetic candidate for transdermal drug delivery that can provide sustained MTF release and enhanced antidiabetic effect.

Differential associations between body composition indices and neurodevelopment during early life in term-born infants: findings from the Pakistan cohort: Multi-Center Body Composition Reference Study.

OBJECTIVE: We examined associations between fat free mass (FFM) and fat mass (FM) accretion during the first 1000 days of life and neurodevelopment in term-born, low-risk infants from Karachi, Pakistan. DESIGN: Prospective, observational study nested within the larger Multi-Center Body Composition Reference Study. FFM, FM, and fat% were estimated using measured deuterium dilution method. Neurodevelopmental outcomes were assessed at 24 months on the INTER-NDA (INTERGROWTH-21st Project Neurodevelopment Assessment) (n = 132). RESULTS: Children with gross motor delays had significantly lower FFM at 18 months (8.01 ± 0.97 kg vs. 7.55 ± 0.20 kg). Children with positive and negative behavior problems had significantly higher fat% at 24 months (20.62 ± 4.30% vs. 18.23 ± 5.46%) and 20.89 ± 4.24% vs. 18.54 ± 5.38%). No associations remained significant after adjusting for covariates. Trajectory modeling showed that between 12 and 18 months, negative behavior scores changed by 13.8 points for every standard deviation change in fat accretion. CONCLUSIONS: Our findings highlight the importance of balancing neurodevelopment and metabolic risk when designing nutritional interventions for young children.

A Shallow Autoencoder Framework for Epileptic Seizure Detection in EEG Signals.

This paper presents a trainable hybrid approach involving a shallow autoencoder (AE) and a conventional classifier for epileptic seizure detection. The signal segments of a channel of electroencephalogram (EEG) (EEG epochs) are classified as epileptic and non-epileptic by employing its encoded AE representation as a feature vector. Analysis on a single channel-basis and the low computational complexity of the algorithm allow its use in body sensor networks and wearable devices using one or few EEG channels for wearing comfort. This enables the extended diagnosis and monitoring of epileptic patients at home. The encoded representation of EEG signal segments is obtained based on training the shallow AE to minimize the signal reconstruction error. Extensive experimentation with classifiers has led us to propose two versions of our hybrid method: (a) one yielding the best classification performance compared to the reported methods using the k-nearest neighbor (kNN) classifier and (b) the second with a hardware-friendly architecture and yet with the best classification performance compared to other reported methods in this category using a support-vector machine (SVM) classifier. The algorithm is evaluated on the Children's Hospital Boston, Massachusetts Institute of Technology (CHB-MIT), and University of Bonn EEG datasets. The proposed method achieves 98.85% accuracy, 99.29% sensitivity, and 98.86% specificity on the CHB-MIT dataset using the kNN classifier. The best figures using the SVM classifier for accuracy, sensitivity, and specificity are 99.19%, 96.10%, and 99.19%, respectively. Our experiments establish the superiority of using an AE approach with a shallow architecture to generate a low-dimensionality yet effective EEG signal representation capable of high-performance abnormal seizure activity detection at a single-channel EEG level and with a fine granularity of 1 s EEG epochs.

Co-delivery of amphotericin B and pentamidine loaded niosomal gel for the treatment of Cutaneous leishmaniasis.

Topical drug delivery is preferable route over systemic delivery in case of Cutaneous leishmaniasis (CL). Among the available agents, amphotericin B (AmB) and pentamidine (PTM) showed promising result against CL. However, monotherapy is associated with incidences of reoccurrence and resistance. Combination therapy is therefore recommended. Thin film hydration method was employed for amphotericin B-pentamidine loaded niosomes (AmB-PTM-NIO) preparation followed by their incorporation into chitosan gel. The optimization of AmB-PTM-NIO was done via Box Behnken Design method and in vitro and ex vivo analysis was performed. The optimized formulation indicated 226 nm particle size (PS) with spherical morphology, 0.173 polydispersity index (PDI), -36 mV zeta potential (ZP) and with entrapment efficiency (EE) of 91% (AmB) and 79% (PTM), respectively. The amphotericin B-pentamidine loaded niosomal gel (AmB-PTM-NIO-Gel) showed desirable characteristics including physicochemical properties, pH (5.1 ± 0.15), viscosity (31870 ± 25 cP), and gel spreadability (280 ± 26.46%). In vitro release of the AmB and PTM from AmB-PTM-NIO and AmB-PTM-NIO-Gel showed more prolonged release behavior as compared to their respective drug solution. Higher skin penetration, greater percentage inhibition and lower IC50 against the promastigotes shows that AmB-PTM-NIO has better antileishmanial activity. The obtained findings suggested that the developed AmB-PTM-NIO-Gel has excellent capability of permeation via skin layers, sustained release profile and augmented anti-leishmanial outcome of the incorporated drugs.

Mannosylated imiquimod-terbinafine co-loaded transethosomes for cutaneous leishmaniasis; assessment of its anti-leishmanial potential, in vivo safety and immune response modulation.

Current treatment options for cutaneous leishmaniasis are associated with myriad limiting factors including low penetration, poor efficacy, and drug toxicities. Herein, we reported imiquimod and terbinafine co-loaded mannosylated transethosomes (IMQ-TER-MTES) with enhanced cutaneous retention, macrophage targeting, anti-leishmanial potential, and dermal immunomodulation. IMQ-TER-MTES were optimized using Design Expert® followed by their loading into chitosan gel. Moreover, the antileishmanial response against amastigotes-infected macrophages and Leishmania-infected BALB/c mice was evaluated. Finally, the safety and immunomodulation activity of IMQ-TER-MTES gel was performed using BALB/c mice. Optimized IMQ-TER-MTES showed nano-sized particles with low poly-dispersibility index (PDI) and high drug entrapment. Mannosylation has augmented macrophage targeting and the internalization capability of TES. IMQ-TER-MTES showed significantly reduced IC50 value (19.56 ± 3.62 µg/ml), higher selectivity index (29.24), and synergism against Leishmania major (L. major) amastigotes. In L. major infected BALB/c mice, the cutaneous lesion healing potential of IMQ-TER-MTES was also elevated with reduced lesion size (1.52 ± 0.43 mm). Superior safety of IMQ-TER-MTES was observed in BALB/c mice along with adequate stimulation of dermal immune cells, in contrast to the ALDARA®. Moreover, incremented Nuclear factor Kappa-ß (NF-κß) and nitric oxide (NO) biosynthesis were observed with IMQ-TER-MTES.

Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout.

BACKGROUND: Allopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo. METHODOLOGY: ALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension. RESULTS: The optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague-Dawley rats after transdermal administration as compared to oral ALP suspension. CONCLUSION: ALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis.

Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (-26.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC50) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG.

Triple-combination therapy for cutaneous leishmaniasis using detergent-free, hyaluronate-coated elastic nanovesicles.

Aim: To develop and evaluate detergent-free, triple-drug-loaded, hyaluronate-coated elastic nanovesicles (H-ENVs) for the topical treatment of cutaneous leishmaniasis. Materials & methods: H-ENVs were developed and evaluated for vesicle size, entrapment efficiency, skin permeation and antileishmanial potential. Results: A 15.7 and 28.6% decrease in the cytotoxicity of paromomycin and amphotericin B, respectively, was observed in detergent-free ENVs compared with conventional ENVs. H-ENVs improved the efficacy of paromomycin against promastigote and amastigote models of leishmaniasis by 4- and 7.5-fold, respectively. In vivo investigation of H-ENVs demonstrated efficient topical management of cutaneous leishmaniasis. Conclusion: The results indicate the potential of H-ENVs as a safe topical treatment choice for cutaneous leishmaniasis.

Application of topical gel is an attractive alternative to oral or intravenous administration of drugs and is likely to deliver a higher dose of the drug to the target site with only rare systemic adverse effects. Nanotechnology-based topical drug delivery is an attractive aspect of pharmaceutical sciences that expresses interest in the topical treatment of cutaneous leishmaniasis. The authors' research focuses on the development and evaluation of novel multidrug-loaded, detergent-free nanovesicles for the simple and effective topical treatment of cutaneous leishmaniasis.

Antileishmanial Agents Co-loaded in Transfersomes with Enhanced Macrophage Uptake and Reduced Toxicity.

The prime objective of this study was to develop amphotericin B (AMB) and rifampicin (RIF) co-loaded transfersomal gel (AMB-RIF co-loaded TFG) for effective treatment of cutaneous leishmaniasis (CL). AMB-RIF co-loaded TF was prepared by the thin-film hydration method and was optimized based on particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (%EE), and deformability index. Similarly, AMB-RIF co-loaded TFG was characterized in terms of rheology, spread ability, and pH. In vitro, ex vivo, and in vivo assays were performed to evaluate AMB-RIF co-loaded TF as a potential treatment option for CL. The optimized formulation had vesicles in nanosize range (167 nm) with suitable PDI (0.106), zeta potential (- 19.05 mV), and excellent %EE of RIF (66%) and AMB (85%). Moreover, it had appropriate deformability index (0.952). Additionally, AMB-RIF co-loaded TFG demonstrated suitable rheological behavior for topical application. AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG showed sustained release of the incorporated drugs as compared to AMB-RIF suspension. Furthermore, RIF permeation from AMB-RIF co-loaded TF and AMB-RIF co-loaded TFG was enhanced fivefold and threefold, whereas AMB permeation was enhanced by eightfold and 6.6-fold, respectively. The significantly different IC50, higher CC50, and FIC50 (p < 0.5) showed synergistic antileishmanial potential of AMB-RIF co-loaded TF. Likewise, reduced lesion size and parasitic burden in AMB-RIF co-loaded TF-treated mouse group further established the antileishmanial effect of the optimized formulation. Besides, AMB-RIF co-loaded TFG showed a better safety profile. This study concluded that TFG may be a suitable carrier for co-delivery of AMB-RIF when administered topically for the treatment of CL.

A cutback in Imiquimod cutaneous toxicity; comparative cutaneous toxicity analysis of Imiquimod nanotransethosomal gel with 5% marketed cream on the BALB/c mice.

Herein, Imiquimod (IMQ) was incorporated in nanotransethosomes (nTES) to develop the IMQ-nTES nano-drug delivery system. IMQ-nTES was optimized using 23 factorial design. The optimized formulation was expressed with a particle size of 192.4 ± 1.60 nm, Poly-dispersibility of 0.115 ± 0.008, and IMQ percent entrapment efficiency of 91.05 ± 3.22%. Smooth and round morphology of IMQ-nTES vesicles was confirmed by TEM micrographs. Moreover, FTIR results have shown drug-excipient compatibility. The IMQ-nTES was laden inside the low molecular weight chitosan gel, which exhibited easy application, spreadability and no irritation to the applied skin. The release pattern has clearly exhibited improved dissolution properties of IMQ with the provision of the sustain release pattern. Higher IMQ content was deposited in deeper epidermis and dermis with IMQ-nTES gel, in contrast to ALDARA. In vivo, comparative toxicity study on BALB/c mice has shown significantly reduced (p < 0.001) psoriatic area severity index (PASI) score and less increment in ear thickness. Epidermal hyperplasia was an obvious finding with ALDARA which was, providentially, minimal in IMQ-nTES gel-treated skin. FTIR analysis of skin tissue has shown an enhancement of lipid and protein content in the ALDARA group, however, in the IMQ-nTES group no such change was observed. With ALDARA application, CD4+ T-cells and constitutive NF-κß expression were significantly elevated, in comparison to the IMQ-nTES gel treated group. Moreover, the adequate expression of IFN-γ and cytotoxic CD8+ T-cells were suggesting the preserved IMQ efficacy with IMQ-nTES gel. Quantification of cutaneous as well as systemic inflammatory markers has also suggested the reduced psoriatic potential of IMQ-nTES gel. In essence, IMQ-nTES gel can be a suitable alternative to ALDARA owing to its better safety profile.

Aggregation induced emission based fluorenes as dual-channel fluorescent probes for rapid detection of cyanide: applications of smartphones and logic gates.

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes. Based on this principle, fluorescent probes (1a-c) were synthesized, and they displayed excellent aggregation induced emission (AIE) behavior in a H2O/DMF (4 : 1, v/v) mixture due to restrictions in intramolecular charge transfer (ICT). As a comparison, probe 1d was synthesized by installing an electron withdrawing (-NO2) group that surprisingly quenched the aggregation behaviour. Additionally, AIE active probes 1a-c displayed a highly sensitive dual channel (fluorometric and colorimetric) response towards rapid detection of CN-, which is an active toxic material. Probes 1a-c showed selectively enhanced fluorescence emission behavior towards CN- with detection limits of 1.34 ppb, 1.38 ppb, and 1.54 ppb, respectively. The sensing mechanism involves Michael type adduct formation due to the nucleophilic addition reaction of cyanide with probes and was confirmed through 1H NMR titration experiments. In contrast, probe 1d containing an electron withdrawing moiety showed insensitivity towards CN-. Therefore, this study provides the efficient strategy to induce AIE character in fluorescent probes and expands the mechanistic approach toward the sensing of toxic CN-.

Preparation and In Vitro Evaluation of Controlled-Release Matrices of Losartan Potassium Using Ethocel Grade 10 and Carbopol 934P NF as Rate-Controlling Polymers.

Controlled-release formulations are essential for those drugs that require fine tuning of their activity to increase the ratio between therapeutic vs. adverse effects. Losartan potassium is among those drugs whose adverse effects may somehow impair its purported benefits. Previous investigations have been carried out to ascertain the suitability of several polymers for being associated with losartan. This study is focused on the effects of Ethocel grade 10 and Carbopol 934P NF on losartan release. Flow and physical properties were assessed according to the protocols standardized by the pharmacopeia (USP-NF 29), and the drug release in phosphate buffer (pH = 6.8) was measured for 24 h. Data evidenced good to excellent flow and physical properties according to the drug/polymer ratio and the addition of co-excipients. The release rate in 24 h was found to be 63-69% to 79-82% without or with the addition of co-excipients, respectively, following zero-order kinetics. The results also suggest a significant difference with the release profile of a traditional release losartan formulation. The results suggest the suitability of Ethocel grade 10 and Carbopol 934P NF as components of a controlled-release losartan formulation.

Development of AIEE active fluorescent and colorimetric probe for the solid, solution, and vapor phase detection of cyanide: smartphone and food applications.

Apart from environmental implications, the extreme toxicity of cyanide can lead to sudden human death upon prolonged exposure to it. Hence, rapid and low-level on-site detection of cyanide has earned paramount significance in the present era. Therefore, an AIEE active and piezofluorochromic Schiff base (probe 2) was synthesized which exhibited highly selective fluorescence enhancement based nanoscale (LOD; 6.17 nM) detection of CN-. The interaction mode was attributed to the deprotonation of the probe by the cyanide that was confirmed through 1H NMR titration, pH, theoretical studies, and switchable fluorescence response upon the addition of HCl. Advantageously, probe 2 displayed solid and vapor phase recognition of cyanide which is the first of its kind as far as we know. The excellent sensing potential of the probe was satisfactorily applied for the detection of cyanide in food, natural soil, and industrial wastewater. Additionally, probe 2 showed an immediate colorimetric response towards cyanide which was favorably integrated through a smartphone. Finally, the switchable fluorescence response of the probe was used to design an INHIBIT logic gate. Therefore, the multifunctional probe 2 displayed excellent practical potential for cyanide detection which was the ultimate goal of our work.