Nepali Linguistic Validation of the Velopharyngeal Insufficiency Effects on Life Outcomes Instrument: VELO-Nepali.

OBJECTIVE: To translate and validate the velopharyngeal insufficiency (VPI) effects on life outcomes (VELO) instrument into Nepali, and test its internal consistency and validity. DESIGN: Quality-of-life instrument translation and validation. SETTING: Community served by Nepal's craniofacial referral hospital. PARTICIPANTS: Twenty-three postpalatoplasty children with VPI, 19 family guardians of VPI cases, and 29 non-VPI controls. INTERVENTIONS: The VELO instrument was translated to Nepali by 2 independent bilingual translators, reconciled, backward-translated, compared, and modified using patient cognitive interviews. All VPI children, guardians, and controls completed the VELO-Nepali. MAIN OUTCOME MEASURE(S): The VELO internal consistency was evaluated using Cronbach α coefficient. Concurrent validity and discriminant validity were assessed using 2-sample t test: assuming unequal variances. RESULTS: The VELO was translated and optimized using cognitive interviews. The VELO-Nepali demonstrated excellent internal consistency, with Cronbach α coefficients of 0.93, 0.94, and 0.90 for VPI cases, guardians of VPI cases, and non-VPI controls, respectively. The VELO-Nepali exhibited strong discriminant validity between VPI cases (x¯ = 45.4, standard deviation [SD] = 22.1) and non-VPI controls (x¯ = 84.9, SD = 12.3), (P < .001). The VELO-Nepali showed strong concurrent validity with similarities in VPI case scores (x¯ = 45.4, SD = 22.1), and guardian scores (x¯ = 52.9, s = 22.8; P = .473). CONCLUSION: The translated VELO-Nepali demonstrates strong internal consistency, discriminant validity, and concurrent validity, and can assess quality of life for Nepali VPI patients. This instrument represents the first VPI quality of life assessment validated in Nepali, and supports the feasibility of its implementation in other low- and low-middle-income countries.

Review of Phytosomes and Ethosomes: Groundbreaking Approaches for Delivering the Phytochemical Components of Plants.

Phytoconstituents have been widely used since ancient times to form a complex with phospholipids due to their various therapeutic actions. Despite having strong pharmacodynamic efficiency, numerous phytoconstituents have shown lower in vivo bioavailability and few adverse effects. Phytochemicals soluble in water exhibit poor absorption, leading to a limited therapeutic impact. Phytosome nanotechnology overcomes this limitation by creating a bound of phytochemicals with phospholipids. This method exhibits improved absorption because phytosomes inhibit significant herbal extract components from being degraded by gastric juices and gut flora. This improves bioavailability, increases clinical benefit, and ensures delivery to tissues without compromising nutritional stability. This review also aims to highlight those vesicular systems that could be used in phytosome technology. Additionally, this review highlights the preparation, advantage, characterization, applications, and recent development of phytosome and ethosome with a list of recent patents and marketed formulations and their uses.

Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

OBJECTIVE: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. MATERIALS AND METHODS: Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. RESULTS: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. CONCLUSION: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

Nanotheranostics: The Fabrication of Theranostics with Nanoparticles and their Application to Treat the Neurological Disorders.

BACKGROUND: Theranostics is a method that focuses on providing patient-centred care and is evolving as a targeted, safe, and effective pharmacotherapy. Nanotheranostics combines diagnosis and therapeutic modalities that bridge traditional treatment and personalised medicine. Theranostics provides novel ideas for nanotechnology. This review describes the current state of nanotechnology-based therapies used to treat neurological illnesses. Some patents on theranostics are also discussed in this review. OBJECTIVE: This study aims to provide a more comprehensive review of the diagnosis and therapeutic properties of nanotheranostics, the present state of nanotechnology-based treatment of neurological disorders, and the future potential of theranostics. METHOD: The phrase "theranostics" refers to a treatment strategy that integrates therapeutics and diagnostics to monitor treatment response and enhance drug efficacy and safety. Theranostics is a crucial component of personalised medicine and calls for significant advancements in predictive medicine. The term "theranostics" refers to a diagnosis that screens patients for potential adverse drug reactions and targets drug delivery depending on the test results. Theranostics treats neurological disorders (like brain tumours (glioma), Parkinson's disease, Alzheimer's disease, and neurovascular diseases). Many review articles on Google Scholar, PubMed, Google Patents, and Scopus were used to gather information for this review. Data acquired from many sources was compiled in this review to provide more information on theranostics. RESULT: The role of various nanocarrier systems as theranostic agents for neurological illnesses and the fabrication of nanomaterials for theranostics are discussed in this article after evaluating a substantial number of review articles. CONCLUSION: The distinctive intrinsic features of nanoparticles make them useful for functionalization and imaging. Theranostics in nuclear medicine include diagnostic imaging and therapy using the same molecule that is radiolabeled differently or the same medication at various doses. It is possible to determine if a patient will benefit from a given treatment by visualising potential targets. Targeted nuclear therapy has been shown to be beneficial in patients if chosen carefully and has a good safety profile.

A task-shifted speech therapy program for cleft palate patients in rural Nepal: Evaluating impact and associated healthcare barriers.

INTRODUCTION: Though access to surgical care for cleft lip/palate has expanded in low- and middle-income countries (LMICs), post-palatoplasty speech therapy is often lacking due to limited healthcare infrastructure and personnel. This mixed-methods study seeks to: 1) evaluate the impact of task-shifted speech therapy on a standardized speech score; 2) describe the experiences of families with post-operative cleft care and associated barriers; and 3) understand how to optimize cleft care by exploring the experiences of children who had nominal improvements after task-shifted speech therapy. METHODS: A convergent parallel mixed-methods study was conducted in Nepal. Standardized speech scores were compared by a blinded speech-language pathologist before and after the speech intervention. Semi-structured interviews (SSIs) and focus groups with families evaluated cleft care experiences and barriers. Qualitative and quantitative data were merged and analyzed. RESULTS: Thirty-nine post-palatoplasty children with speech deficits (ages 3-18) underwent task-shifted speech therapy, and demonstrated significant improvements in composite speech scores targeted by exercises (p<0.0001) and weakness (p=0.0002), with improvements in misarticulation (p=0.07) and glottal stop (p=0.05) that trended towards significance. Forty-seven SSIs demonstrated that the greatest barriers to follow-up were family responsibilities (62%), travel/distance (53%), and work (34%). In five focus groups, families expressed a desire to improve their child's speech and seek formal speech therapy. The speech intervention was found to be beneficial because of the compassionate staff, free lodging/food, and ability to socialize with other cleft patients and families. After merging quantitative and qualitative data, we noted that younger children between 3 and 5 years old and families who traveled greater distances for healthcare access benefited less from the speech therapy intervention. CONCLUSIONS: Task-shifted speech therapy has the potential to improve cleft lip/palate speech in LMICs. Multiple biosocial issues limit access to appropriate post-operative care.

Development and evaluation of isradipine via rutin-loaded coated solid-lipid nanoparticles.

The objective was to develop a stable and non-compliance coated solid-lipid nanoparticles (coated SLN) using polymer (Eudragit L100) and lipoid (glycerol monostearate: soya lecithin) for partial dose reduction of isradipine [ISR; 2.5 mg by combination of bioenhancing agent (rutin; Ru) in equivalent ratio]. The physicochemical characterizations were performed by FT-IR and DSC of elected model drug (ISR), drug mixer with Ru/polymer and coated SLN with Ru (ONbp); the resulted distinctive peaks demonstrated that no chemical interaction and incompatibility found between them. The plasma samples of formulation (ONbp) were analyzed by liquid chromatography (HPLC) using UV-spectrometer. Data were integrated and analyzed with the help of a computer-designed program "Kinetica Software" (Thermo Scientific Kinetica, PK/PD Analysis, version 5.0, Philadelphia, PA). The pharmacokinetic study showed 3.2- to 4.7-folds enhancement in oral bioavailability of coated SLN of ISR with Ru (ONbp) when compared to a coated formulation of ISR without Ru (ONps) and conventional drug suspension. In vivo studies were revealed significantly at greater extent in (drug stability and solubility) oral absorption, which has shown potential entrapment efficiency (97.85% ± 1.02%) to improve biological activity against hypertension. Hence, nano-system of ISR against hypertension is achieved with consequent dose reduction with enhanced systemic bioavailability.

Design, Optimization and Characterization of Granisetron HCl Loaded Nano-gel for Transdermal Delivery.

BACKGROUND & OBJECTIVE: Our research objective was to design, develop, optimize and characterize Granisetron HCl transdermal gel in order to minimize side effects associated with oral delivery. METHOD: A statistical design was practically applied for further optimization and preparation of transfersomal gel using Box-Behnken methodology at three levels. The selected independent and dependent variables were Lipoid, surfactant and sonication time and encapsulation efficiency, size and flux correspondingly. RESULT: The optimized formulation (GTV-16) morphology, shape, size, potential, encapsulation capacity and flux (using Franz-diffusion cell assembly via animal skin barricade medium) were determined. Then, GTV-16 incorporated into gel and during evaluation nano-transformal gel has good particle size of 127.7±1.08 nm, better entrapment efficiency of 83.0 ± 3.22 % and flux of 20.0 ± 1.88µgcm-2/h. CONCLUSION: The results demonstrated that Granisetron Hydrochloride loaded nano-gel was significantly superior with 8.5 fold enhancement in bioavailability as compared with drug solution.

Nano-colloidal carrier via polymeric coating for oral delivery of isradipine.

Our research objective was to develop, characterize, and optimize stable form of nano-colloidal carrier with Eudragit-coated solid lipid nanobioparticles (SLNbp) for oral delivery of isradipine (ISR). To achieve, a three factors, i.e., lipid-to-surfactant ratio (A, % w/w), Eudragit L100 (B, % w/w), and sonication time (C, minutes) at three levels (-1 and +1 levels of quality central level) was applied to develop SLNbp using response surface methodology at constant ratio of ISR and rutin. The second-order polynomial quadratic equations of responses [R1, R2, and R3; entrapment efficiency (EE), particle size, and drug release] were constructed and also plotted response surface (two- and three-dimensional) plots. The derived polynomial equation and 2D and 3D model were showed the relationship between the responses of the selected independent variables (A, B, and C). The model validation and optimization was performed by numerical checkpoint analysis to predict the optimized solid lipid nanobioparticle formulas (ONbp 1-10). The optimized formulations prepared and during evaluation ONbp 3 has better smaller particle size (106 nm), sustainable release (95.61% up to 40 h), higher EE (97.85%), and drug content (99.92% ± 0.08%) during 3-month storage showed good stability. Therefore, its performance can be considered for further development of stable oral drug delivery system of ISR.

Optimization & design of isradipine loaded solid lipid nanobioparticles using rutin by Taguchi methodology.

Our research objective was to optimize and design nano-biosystem of Isradipine (IDP) via novel bioenhancer (Rutin) loaded solid-lipid nanobioparticles (ANbp) using Taguchi design (TgD) methodology. Firstly, preliminary screening of solid lipid nanoparticles (SLNps) formulation core factors (A, B & C; Lipoid's, poly-acid, sonication time respectively at fixed dose of model drug were assessed on entrapment efficiency & particle size; R1 & R2) by performed experimentally of three factor three levels orthogonal L27 array. Consequently, signal to noise (S/N) ratio plot of responses were drawn to predict better quality fitted-levels of significant factor for eminence optimization. Further, optimized quality spaces composition was used via enhancer (Rutin) to design advanced bio-formulation (ANbp) and done its evaluation (entrapment efficiency, particle size, drug release & kinetics). As designed, ANbp results showed better sustained (86.54% as compared to control SLNps 94.48% in 24h) release, kinetics & stability behavior with good entrapment efficiency (97.58%) and desired smaller particle size (108nm). Therefore, statistically (TgD) optimization strategy would be considered to design nano-drug delivery system with bio-agent in-order to improve oral bioavailability of antihypertensive agents.

Comparison of Umbilical Cord Milking and Delayed Cord Clamping on Cerebral Blood Flow in Term Neonates.

OBJECTIVE: To compare the effect of umbilical cord milking (UCM) and delayed cord clamping (DCC) on cerebral blood flow in term neonates. METHODS: This randomized controlled trial was conducted at a teaching hospital in India during 2012 to 2013. Two hundred newborns (>36wk) were randomized to UCM and DCC groups. UCM was done on 25cm of cord length. In DCC group, clamping was delayed by 60 to 90s. Resistive Index (RI), Pulsatility Index (PI) and cerebral blood flow velocities of middle cerebral artery (MCA) were measured at 24 to 48h of life. RESULTS: Baseline characteristics and hemodynamic parameters were comparable. Mean PI [1.18 (0.26)] and RI [0.65 (0.08)] in UCM group was comparable to mean PI [1.18 (0.25)] and RI [0.65 (0.08)] in DCC group. The peak systolic velocity and end diastolic velocity (cm/s) of blood flow in MCA for UCM group were 34.94 (11.82) and 11.71 (4.75) respectively, while in DCC group they were 37.24 (12.63) and 13.07 (4.78) (p 0.23 and 0.07) respectively. Indices among growth retarded babies were not different. CONCLUSIONS: DCC and UCM had similar effect on cerebral blood flow velocities and Doppler indices in MCA, in term neonates.

Taguchi design for optimization and development of antibacterial drug-loaded PLGA nanoparticles.

This research report was to develop Cefixime loaded polylactide-co-glycolide (PLGA) nanoparticles using modified precipitation method. TEM analysis indicated formation of well-formed, smooth, spherical nanoparticles with no aggregates whereas XRD recommended dispersion of drug in PLGA carrier system in amorphous form. The polymer and stabilizer concentration and organic to aqueous ratio were found to be significant factors for nanoparticles and their optimization using Taguchi design (L9). The design formulations showed entrapment efficiency (EE), particle size and poly-dispersity index (PDI) ranging 68.31 ± 1.74%, 159.8-157.7 nm and 0.126-0.149, respectively indicated small and stable nanoparticles with good homogeneity and encapsulation. The design optimized formulation drug release and permeation studies demonstrated that it is four times sustained release behavior and 1.74 times better permeation than free drug. The result of microbiological assay also suggested that optimized formulation has significant antibacterial activity against intracellular multidrug resistance (MDR) of Salmonella typhi.

A novel nano-carrier transdermal gel against inflammation.

The objective was to develop a stable, reproducible and patient non-infringing novel transdermal drug delivery system "nano-carrier transdermal gel" (NCTG) in combination of partial dose replacement of diclofenac diethylamine (DDEA) by curcumin (CRM). The drug content of gel was 99.30 and 97.57% for DDEA and CRM. Plasma samples were analyzed by liquid chromatography with triple-quadrupole tandem mass spectrometer (LC-MS/MS). Data were integrated with Analyst™ and analyzed by WinNonlin; stability parameters were analyzed using Tukey-Kramer multiple comparison test. Its average skin irritation scored 0.49 concluded to be non-irritant, safe for human use and in vivo studies revealed significantly greater extent of absorption and highly significant inhibition (%) of carrageenan induced paw edema. The results also demonstrated that encapsulation of drugs in nano-carrier increases its biological activity due to superior skin penetration potential. Hence, a novel once day transdermal gel of nano-carrier (nano-transfersomes; deformable vesicular) is achieved, to increase systemic availability, subsequent reduction in dose and toxicity of DDEA was developed for the treatment of inflammation.

Nano-transfersomes as a novel carrier for transdermal delivery.

The aim of this study was to design and optimize a nano-transfersomes of Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3(3) factorial design (Box-Behnken) was used to derive a polynomial equation (second order) to construct 2-D (contour) and 3-D (Response Surface) plots for prediction of responses. The ratio of lipid to surfactant (X1), weight of lipid to surfactant (X2) and sonication time (X3) (independent variables) and dependent variables [entrapment efficiency of DDEA (Y1), entrapment efficiency of CRM (Y2), effect on particle size (Y3), flux of DDEA (Y4), and flux of CRM (Y5)] were studied. The 2-D and 3-D plots were drawn and a statistical validity of the polynomials was established to find the compositions of optimized formulation. The design established the role of the derived polynomial equation, 2-D and 3-D plots in predicting the values of dependent variables for the preparation and optimization of nano-transfersomes for transdermal drug release.

Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers.

The aim of the study was to develop and optimize Piroxicam transdermal gel formulation using three-factor, three-level Box-Behnken design by deriving a second-order polynomial equation to construct contour plots for prediction of responses as three selected independent variables with ratio of carbopol 974 (X1), ratio of propylene glycol (PG) (X2) and ratio of ethanol (X3). The dependent variables studied were the skin permeation rate of piroxicam (Y1), viscosity of the gel (Y2) and pH of the gel (Y3). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the vertical Franz-type diffusion cell. The permeation rate of piroxicam increased proportionally with ethanol concentration but decreased with polymer concentration. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation.

Optimization and formulation design of gels of Diclofenac and Curcumin for transdermal drug delivery by Box-Behnken statistical design.

The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release.

Mechanism of action of flavonoids as anti-inflammatory agents: a review.

Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a variety of biological effects both in vitro and in vivo. They have been found to have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic, mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic, antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. They have been found to have anti-inflammatory activity in both proliferative and exudative phases of inflammation. Several mechanisms of action have been proposed to explain anti-inflammatory action of flavonoids. The aim of the present review is to give an overview of the mechanism of action of potential anti-inflammatory flavonoids.

Chemical penetration enhancers: a patent review.

BACKGROUND: Ever since transdermal drug delivery came into existence, it has offered great promises, although most of them are yet to be fulfilled owing to some intrinsic restrictions of the transdermal route. On the positive side, transdermal drug delivery systems present advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The greatest hindrance in the percutaneous delivery is the obstruction property of the stratum corneum, the outermost layer of the skin, in addition to usual problems such as skin binding, skin metabolism, cutaneous toxicity and prolonged lag times. OBJECTIVE: This paper reviews investigations on the feasibility and application of penetration enhancers as described in recent patents, which help in the selection of a suitable sorption promoter(s) for enhanced delivery of medicaments through the skin. METHOD: The patents granted under various categories of penetration enhancers have been discussed including fatty acids, terpenes, fatty alcohol, pyrrolidone, sulfoxides, laurocapram, surface active agents, amides, amines, lecithin, polyols, quaternary ammonium compounds, silicones, alkanoates and so on. CONCLUSION: Scores of promising chemicals have been harnessed for their skin permeation promoting capacity as mentioned earlier. In future, many more chemicals and putative enhancers are likely be documented and patented.