Nanovesicles as Potential Carriers for Delivery of Antiviral Drugs: A Comprehensive Review.

Different nanocarriers-based strategies are now extensively being used as an important strategy for improving drug efficacy and responsiveness, reducing toxicity issues related to drugs and harmful side effects, and overcoming the numerous significant difficulties related to absorption and bioavailability. Amongst different nanocarriers, nanovesicles are excellent and versatile systems for effectively delivering biomolecules, drugs, and targeted ligand distribution and location. Nanovesicles are nanosized self-assembling spherical capsules with an aqueous core and one/more lipid(s) layers. Several synthetic nanovesicles have been developed and investigated for their prospective uses in delivering drugs, proteins, peptides, nutrients, etc. Important procedures for nanovesicle manufacturing are thin-film hydration, unshaken method, ethanol injection, ether injection, proliposomes, freeze-drying, hot method, cold method, reverse-phase evaporation, and ultrasonication. Liposomes, liposomes, ethosomes, exosomes, and transferosomes (elastic vesicles) are the nonvesicular candidates extensively investigated to deliver antiviral drugs. This review article comprehensively reviews different nanovesicles, their compositions, manufacturing, and applications as potential carriers for effectively delivering different antiviral drugs to treat viral diseases.

Population infection estimation from wastewater surveillance for SARS-CoV-2 in Nagpur, India during the second pandemic wave.

Wastewater-based epidemiology (WBE) has emerged as an effective environmental surveillance tool for predicting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease outbreaks in high-income countries (HICs) with centralized sewage infrastructure. However, few studies have applied WBE alongside epidemic disease modelling to estimate the prevalence of SARS-CoV-2 in low-resource settings. This study aimed to explore the feasibility of collecting untreated wastewater samples from rural and urban catchment areas of Nagpur district, to detect and quantify SARS-CoV-2 using real-time qPCR, to compare geographic differences in viral loads, and to integrate the wastewater data into a modified Susceptible-Exposed-Infectious-Confirmed Positives-Recovered (SEIPR) model. Of the 983 wastewater samples analyzed for SARS-CoV-2 RNA, we detected significantly higher sample positivity rates, 43.7% (95% confidence interval (CI) 40.1, 47.4) and 30.4% (95% CI 24.66, 36.66), and higher viral loads for the urban compared with rural samples, respectively. The Basic reproductive number, R0, positively correlated with population density and negatively correlated with humidity, a proxy for rainfall and dilution of waste in the sewers. The SEIPR model estimated the rate of unreported coronavirus disease 2019 (COVID-19) cases at the start of the wave as 13.97 [95% CI (10.17, 17.0)] times that of confirmed cases, representing a material difference in cases and healthcare resource burden. Wastewater surveillance might prove to be a more reliable way to prepare for surges in COVID-19 cases during future waves for authorities.

Wound Healing Activity of Topical Herbal Gels Containing Barringtonia acutangula Fruit Extract: In silico and In vivo Studies.

The current study describes the efficacy of B. acutangula fruit extract in wound healing via incorporation within topical gels. B. acutangula fruit extract was produced by solvent extraction method. The bioactive extract was incorporated within Carbopol 940-based topical gels, which were applied topically over the excision and incision wounds. The change in healing process was observed till 20 days. The percentages of closure of excision wound area were 92.89 % and 93.43 %, when treated with topical herbal gels containing B. acutangula fruit extract of 5 % and 10 %, respectively. The tensile strengths of incision area in rats treated with topical herbal gels containing 5 % and 10 % methanol extract of B. acutangula fruits were found to be 25±5.12 g and 30±4.10 g, respectively. The wound healing activity of topical herbal gels containing B. acutangula fruit extract in rats was found to be significant when compared with that of the reference standard and untreated groups. In addition, in silico studies suggested about good skin permeability and binding to the proteins responsible for delaying wound healing. It can be concluded that this topical herbal gels containing B. acutangula fruit extract could be used clinically for the treatment of wounds.

Lipid-Gelucire based rectal delivery of ramipril prodrug exhibits significant lowering of intra-ocular pressure in normotensive rabbit: sustained structural relaxation release kinetics and IVIVC.

Carboxylesterase enzymes convert a prodrug ramipril into the biologically active metabolite ramiprilat. It is prescribed for controlling ocular hypertension after oral administration. High concentrations of carboxylesterase enzymes in rectal and colon tissue can transform ramipril significantly to ramiprilat. Sustained rectal delivery of ramipril has been developed for intra-ocular pressure lowering effect using a normotensive rabbit model. Rectal suppositories have been formulated using a matrix base of HPMC K100-PEG 400-PEG 6000, incorporating varying amounts of Gelucire by the fusion moulding method. The presence of Gelucire in the suppository exhibited sustained structural relaxation-based release kinetics of RM compared to its absence. Intravenous and oral administration of ramipril has decreased IOP in the treated rabbit up to 90 and 360 min, respectively. Treated rabbits with suppositories have revealed decreased IOP for an extended period compared to the above. Formulation containing GEL 3% reduced intra-ocular pressure to 540 min, with the highest area under the decreased IOP curve. Compared to oral, the pharmacodynamic bioavailability of ramipril has been improved significantly using a sustained-release rectal suppository. A rectal suppository for sustained delivery of ramipril could be used to lower IOP significantly.

Influence of Nano-Particulate Impurities and ß-glucans on the Stability of Protein-Based Formulations.

Pharmaceutical grade sugars manufactured under Current Good Manufacturing Practice (cGMP) and complied with International Pharmaceutical Excipients Council (IPEC) quality standards, also contain a significant amount of nano-particulate impurities (NPIs). This review will focus on the origin of NPIs, the mechanism of their interference with Dynamic light scattering (DLS) and endotoxin tests, filtration technology to effectively reduce the NPIs, methodologies for analytical quantification of NPIs, guidance for setting the limits of threshold concentration and the overall impact of NPIs on the therapeutic activity, performance, stability of biopharmaceuticals and protein-based formulations. NPIs with an average particle size of 100 to 200 nm are present in sugars and are a combination of various chemicals such as dextrans (with the presence of ß-glucans), ash, inorganic metal salts, aromatic colorants, etc. These NPIs primarily originate from raw materials and cannot be removed during the sugar refinement process. While it is commonly believed that filtering the final formulation with a 0.22 µ sterilizing grade filter removes all microbes and particles, it is important to note that NPIs cannot be filtered using this standard sterile filtration technology. Exceeding the threshold limit of NPIs can have detrimental effects on formulations containing proteins, monoclonal Antibodies (mAbs), nucleic acids, and other biopharmaceuticals. NPIs and ß-glucans have a critical impact on the functionality and therapeutic activity of biomolecules and if present below the threshold limit of reaction, stability and shelf-life of biologics formulation will be greatly improved and the risk of immunogenic reactions must be significantly decreased.

Surface Tailoring-Modulated Bifunctional Oxygen Electrocatalysis with CoP for Rechargeable Zn-Air Battery and Water Splitting.

The transition metal phosphide (TMP)-based functional electrocatalysts are very promising for the development of electrochemical energy conversion and storage devices including rechargeable metal-air batteries and water electrolyzer. Tuning the electrocatalytic activity of TMPs is one of the vital steps to achieve the desired performance of these energy devices. Herein, we demonstrate the modulation of the bifunctional oxygen electrocatalytic activity of nitrogen-doped carbon-encapsulated CoP (CoP@NC) nanostructures by surface tailoring with ultralow amount (0.56 atomic %) of Ru nanoparticles (2.5 nm). The CoP at the core and the Ru nanoparticles on the shell have a facile charge transfer interaction with the encapsulating NC. The strong coupling of Ru with CoP@NC boosts the electrocatalytic performance toward oxygen reduction (ORR), oxygen evolution (OER), and hydrogen evolution (HER) reactions. The surface-tailored catalyst requires only 35 mV to deliver the benchmark current density of 10 mA·cm-2 for HER. A small potential gap of 620 mV between ORR and OER is achieved, making the catalyst highly suitable for the development of rechargeable zinc-air batteries (ZABs). The homemade ZAB delivers a specific capacity of 780 mA·hgZn-1 and peak power density of 175 mW·cm-2 with a very small voltaic efficiency loss (1.1%) after 300 cycles. The two-electrode water splitting cell (CoP@NC-Ru||CoP@NC-Ru) delivers remarkably low cell voltage of 1.47 V at the benchmark current density. Stable current density of 25 mA·cm-2 for 25 h without any significant change is achieved. Theoretical studies support the charge transfer interaction-induced enhanced electrocatalytic activity of the surface-tailored nanostructure.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and use bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population.

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.

Thyme Oil-Containing Fluconazole-Loaded Transferosomal Bigel for Transdermal Delivery.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 µg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections.

Conveyance of sofosbuvir through vesicular lipid nanocarriers as an effective strategy for management of viral meningitis.

This study aimed to deliver a potential water-soluble antiviral drug (sofosbuvir) through optimized vesicular lipid nanocarriers (LNs) to the rat brain as a novel strategy against viral meningitis. A 23 factorial design approach was established to assess the effect of formulation composition and process variables on the physicochemical properties of the LNs. Sofosbuvir-loaded LNs (SLNs) were developed by lipid layer hydration method utilizing optimized parameters and evaluated for various in vitro characterizations like FTIR, DSC, XRD, FESEM, vesicle size, zeta potential, drug carrying capacity and drug release. Plasma and brain pharmacokinetic (PK) studies were conducted in Sprague-Dawley rats. FTIR data depicted the absence of any major interaction between the drug and the excipients. DSC revealed a sharp endothermic peak for the drug. XRD showed the amorphic nature of the SLNs. Optimized SLNs were spherical as depicted from FESEM with 42.43 nm size, -49.21 mV zeta potential, 8.31% drug loading and sustained drug release in vitro. Plasma/brain PK studies depicted significant improvement in key PK parameters, viz. AUC, AUMC, MRT, and Vd, compared to those for the free drug. A more than 3.5-fold increase in MRT was observed for optimized SLNs (11.2 h) in brain tissue compared to the free drug (3.7 h). Ex vivo hemolysis data confirmed the non-toxic nature of the SLNs to human red blood cells. In silico docking study further confirmed strong interaction between the drug and selected protein 4YXP (herpes simplex) with docking score of -7.5 and 7EWQ protein (mumps virus) with docking score of -7.3. The optimized SLNs may be taken for further in vivo studies to pave the way towards clinical translation.

Chitosan-carboxymethyl tamarind gum in situ polyelectrolyte complex-based floating capsules of ofloxacin: In vitro-in vivo studies.

The current research attempted to design and evaluate sustained stomach-specific ofloxacin delivery by single-unit hydrodynamically balanced system (HBS)-based floating capsules. These HBS-based floating capsules of ofloxacin were prepared using two oppositely ionic polymers, namely cationic-natured low molecular mass chitosan (LMMCH) and anionic-natured carboxymethyl tamarind gum (CMTG). FTIR results indicated the in situ formation of a polyelectrolyte complex in-between two oppositely charged polymers (i.e., in-between -NH2 group of the cationic natured LMMCH and -COOH groups of the anionic natured CMTG) and the nonexistence of any drug-polymer interaction(s) within these formulated ofloxacin HBS capsules. All these LMMCH-CMTG ofloxacin HBS capsules exhibited drug content uniformity, a sustained in vitro drug-releasing profile over 10 h. The ofloxacin HBS capsules (formulated with 75 mg LMMCH and 25 mg CMTG), which was selected as best formulation (for further studies), exhibited excellent in vitro floatation behaviour in SGF (pH 1.2) over 6 h without any floating lag-time, whereas the same formulation containing barium sulfate (100 mg) instead of drug demonstrated prolonged stomach-specific gastroretention in an in vivo X-ray imaging study using rabbits. Therefore, these types of HBS floating capsules can be useful for stomach-specific gastroretentive floating delivery of other drugs.

Natural Polymeric Nanobiocomposites for Anti-Cancer Drug Delivery Therapeutics: A Recent Update.

Cancer is one of the most common lethal diseases and the leading cause of mortality worldwide. Effective cancer treatment is a global problem, and subsequent advancements in nanomedicine are useful as substitute management for anti-cancer agents. Nanotechnology, which is gaining popularity, enables fast-expanding delivery methods in science for curing diseases in a site-specific approach, utilizing natural bioactive substances because several studies have established that natural plant-based bioactive compounds can improve the effectiveness of chemotherapy. Bioactive, in combination with nanotechnology, is an exceptionally alluring and recent development in the fight against cancer. Along with their nutritional advantages, natural bioactive chemicals may be used as chemotherapeutic medications to manage cancer. Alginate, starch, xanthan gum, pectin, guar gum, hyaluronic acid, gelatin, albumin, collagen, cellulose, chitosan, and other biopolymers have been employed successfully in the delivery of medicinal products to particular sites. Due to their biodegradability, natural polymeric nanobiocomposites have garnered much interest in developing novel anti-cancer drug delivery methods. There are several techniques to create biopolymer-based nanoparticle systems. However, these systems must be created in an affordable and environmentally sustainable way to be more readily available, selective, and less hazardous to increase treatment effectiveness. Thus, an extensive comprehension of the various facets and recent developments in natural polymeric nanobiocomposites utilized to deliver anti-cancer drugs is imperative. The present article provides an overview of the latest research and developments in natural polymeric nanobiocomposites, particularly emphasizing their applications in the controlled and targeted delivery of anti-cancer drugs.

The role of bixin as antioxidant, anti-inflammatory, anticancer, and skin protecting natural product extracted from Bixa orellana L.

Since long, medicinal plants or herbs are being used in different traditional treatment systems as therapeutic agents to treat a variety of illnesses. Bixa orellana L., an medicinal plant (family: Bixaceae), is an Ayurvedic herb used to treat dyslipidemia, diarrhoea, and hepatitis since ancient times. B. orellana L., seeds contain an orange-red coloured component known as bixin (C25H30O4), which constitutes 80% of the extract.Chemically, bixin is a natural apocarotenoid, biosynthesized through the oxidative degradation of C40 carotenoids. Bixin helps to regulate the Nrf2/MyD88/TLR4 and TGF-1/PPAR-/Smad3 pathways, which further give it antifibrosis, antioxidant, and anti-inflammatory properties. This current review article presents a comprehensive review of bixin as an anti-inflammatory, antioxidant, anticancer,and skin protecting natural product. In addition, the biosynthesis and molecular target of bixin, along with bixin extraction techniques, are also presented.

Dental delivery systems of antimicrobial drugs using chitosan, alginate, dextran, cellulose and other polysaccharides: A review.

Dental caries, periodontal disease, and endodontic disease are major public health concerns worldwide due to their impact on individuals' quality of life. The present problem of dental disorders is the removal of the infection caused by numerous microbes, particularly, bacteria (both aerobes and anaerobes). The most effective method for treating and managing dental diseases appears to be the use of antibiotics or other antimicrobials, which are incorporated in some drug delivery systems. However, due to their insufficient bioavailability, poor availability for gastrointestinal absorption, and pharmacokinetics after administration via the oral route, many pharmaceutical medicines or natural bioactive substances have limited efficacy. During past few decades, a range of polysaccharide-based systems have been widely investigated for dental dug delivery. The polysaccharide-based carrier materials made of chitosan, alginate, dextran, cellulose and other polysaccharides have recently been spotlighted on the recent advancements in preventing, treating and managing dental diseases. The objective of the current review article is to present a brief comprehensive overview of the recent advancements in polysaccharide-based dental drug delivery systems for the delivery of different antimicrobial drugs.

RNA-Seq of untreated wastewater to assess COVID-19 and emerging and endemic viruses for public health surveillance.

Background: The COVID-19 pandemic showcased the power of genomic sequencing to tackle the emergence and spread of infectious diseases. However, metagenomic sequencing of total microbial RNAs in wastewater has the potential to assess multiple infectious diseases simultaneously and has yet to be explored. Methods: A retrospective RNA-Seq epidemiological survey of 140 untreated composite wastewater samples was performed across urban (n = 112) and rural (n = 28) areas of Nagpur, Central India. Composite wastewater samples were prepared by pooling 422 individual grab samples collected prospectively from sewer lines of urban municipality zones and open drains of rural areas from 3rd February to 3rd April 2021, during the second COVID-19 wave in India. Samples were pre-processed and total RNA was extracted prior to genomic sequencing. Findings: This is the first study that has utilised culture and/or probe-independent unbiased RNA-Seq to examine Indian wastewater samples. Our findings reveal the detection of zoonotic viruses including chikungunya, Jingmen tick and rabies viruses, which have not previously been reported in wastewater. SARS-CoV-2 was detectable in 83 locations (59%), with stark abundance variations observed between sampling sites. Hepatitis C virus was the most frequently detected infectious virus, identified in 113 locations and co-occurring 77 times with SARS-CoV-2; and both were more abundantly detected in rural areas than urban zones. Concurrent identification of segmented virus genomic fragments of influenza A virus, norovirus, and rotavirus was observed. Geographical differences were also observed for astrovirus, saffold virus, husavirus, and aichi virus that were more prevalent in urban samples, while the zoonotic viruses chikungunya and rabies, were more abundant in rural environments. Interpretation: RNA-Seq can effectively detect multiple infectious diseases simultaneously, facilitating geographical and epidemiological surveys of endemic viruses that could help direct healthcare interventions against emergent and pre-existent infectious diseases as well as cost-effectively and qualitatively characterising the health status of the population over time. Funding: UK Research and Innovation (UKRI) Global Challenges Research Fund (GCRF) grant number H54810, as supported by Research England.

Anthropometric Analysis of Distal Femur Parameters in the Eastern Uttar-Pradesh Population.

INTRODUCTION: Anthropometric measurements of the distal femoral fragment play a crucial role in prosthesis design during arthroplastic knee surgeries and offer valuable clues for stature estimation in forensic investigations. The present study is an attempt to assess various anthropometric parameters of the distal femur in this regard. MATERIALS AND METHODS: A total of 96 intact dry femora were anthropometrically assessed using digital Vernier calipers. The femoral length was measured using an osteometric table. The torsion angle was calculated with an analog goniometer. The various parameters studied included: medial condyle length and thickness, lateral condyle length and thickness, bicondylar width, intercondylar width, intercondylar depth, torsional angle, and femoral length. The data obtained were statistically analyzed using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: Mean medial condyle length was 57.38±4.47mm and thickness was 24.53±2.27mm. Mean lateral condyle length and thickness were found to be 58.49±4.3mm and 25.33±3.15mm respectively. Mean bicondylar width was 71.96±6.73mm, mean intercondylar width 21.86±2.71mm, and the intercondylar depth 27.04±2.59mm respectively. The average femur length was 41.87±3.31mm and the average torsion angle was 20.19°±6.99°. Significant correlations were observed between distal femoral parameters. Lateral condyle length showed maximum correlation with other parameters. Femur length was found to correlate significantly with all parameters except medial condyle thickness. Torsion angle was significantly correlated with lateral condyle length and femur length only. DISCUSSION: The findings of this study show considerable variation from those of other studies done within India. This proves that distal femoral anthropometry has regional variations. These data can aid sports physicians and orthopedic surgeons with implant designing and forensic experts during investigations.

A comprehensive review on pharmaceutical uses of plant-derived biopolysaccharides.

Biopolysaccharides extracted from plants are mainly photosynthetic byproducts found in leaves, pods, stems, fruits, grains, seeds, corms, rhizomes, roots, bark exudates, and other plant parts. Recently, these plant-derived biopolysaccharides have received a great deal of attention as pharmaceutical excipients in a range of different dosage forms because of several key advantages, such as widespread accessibility from nature as plant-based sources are readily available, sustainable production, availability of easy and cost-effective extraction methodologies, aqueous solubility, swelling capability in the aqueous medium, non-toxicity, biodegradability, etc. The current review presents a comprehensive overview of the uses of plant-derived biopolysaccharides as effective pharmaceutical excipients in the formulations of different kinds of dosage forms, for example gels, pastes, films, emulsions, suspensions, capsules, tablets, nanoparticles, microparticles, beads, buccal formulations, transdermal formulations, ocular formulations, nasal formulations, etc.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy.

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100-200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer.

Dento-skeletal Sequel of Hyrax in Nonsyndromic Cleft Lip and Palate: A Systematic Review and Meta-analysis.

Aim: To critically evaluate and review the dento-skeletal outcomes of hyrax with or without nonsurgical protraction therapy in nonsyndromic cleft lip and palate (CLP) patients. Materials and methods: Electronic databases were searched from PubMed, Cochrane, Scopus, SciELO, Lilacs, and Google Scholar from January 2005 to April 2022 to identify studies reporting on the dento-skeletal effect of hyrax with or without nonsurgical protraction therapy among children aged 7-15 years with CLP before the secondary alveolar bone grafting (SABG) procedure. Abstracts and subsequently eligible full-text articles were screened. The risk of bias in the included randomized and nonrandomized studies was assessed using Cochrane collaboration's risk of bias tool. The random-effects meta-analyses of the mean difference were carried out. Results: A total of 423 studies were identified. After a thorough screening, 19 studies met the inclusion criteria. Of these 19 studies, 13 studies were conducted with only hyrax appliances, six studies had hyrax with nonsurgical protraction therapy. Conclusion: Hyrax had increased intermolar width, anterior nasal cavity width, and posterior maxillary width compared to inverted mini hyrax with p-values = 0.027, 0.004, and 0.03, respectively. Inverted mini hyrax had more canine inclination on noncleft than hyrax. Hyrax and fan-type expanders had an equivalent effect on the dento-skeletal structures indicating that hyrax can be used as an alternative to fan-type expanders. Hyrax with protraction therapy had a remarkable change in ANB angle compared to noncleft patients. How to cite this article: Deepika U, Ray P, Nayak A, et al. Dento-skeletal Sequel of Hyrax in Nonsyndromic Cleft Lip and Palate: A Systematic Review and Meta-analysis. Int J Clin Pediatr Dent 2023;16(6):882-896.