Retraction notice to "Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines" [Heliyon 9 (2023) e16963].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e16963.].

Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride.

OBJECTIVE: The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form. SIGNIFICANCE: Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability. METHOD: In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X1) as gelling agent and hydroxypropyl methyl cellulose K4M (X2) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization. RESULT: Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months. CONCLUSION: It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.

Mechanistic insight into the bioactivity of prodigiosin-entrapped lipid nanoparticles against triple-negative breast, lung and colon cancer cell lines.

This research investigates the potentials of prodigiosin(PG) derived from bacteria and its formulations against triple-negative breast (TNB), lung, and colon cancer cells. The PG was extracted from S. marcescens using continuous batch culture, characterized, and formulated into lyophilized parenteral nanoparticles (PNPs). The formulations were characterized with respect to entrapment efficiency (EE), DSC, FT-IR, TEM, and proton nuclear magnetic resonance (1H NMR) spectroscopy. In vitro drug release was evaluated in phosphate buffer (pH 7.4) while acute toxicity, hematological and histopathological studies were performed on rats. The in vitro cytotoxicity was evaluated against TNB (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines. High EE (92.3 ± 12%) and drug release of up to 89.4% within 8 h were obtained. DSC thermograms of PG and PG-PNPs showed endothermic peaks indicating amorphous nature. The FT-IR spectrum of PG-PNPs revealed remarkable peaks of pure PG, indicating no strong chemical interaction between the drug and excipients. The TEM micrograph of the PG-PNPs showed nano-sized formulations (20-30 nm) whose particles were mostly lamellar and hexagonal structures. The 1H NMR result revealed the chemical structure of PG showing all assigned proton chemical shifts. Toxicity results of the PG and its formulation up to a concentration of 5000 mg/kg showed insignificant vacuolar changes of hepatocytes in the liver, with normal renal medulla and cortex in the kidney. The PG and PG-PNPs inhibited the growth of breast, lung, and colon cell lines. The nano-sized lipid formulation (PG-PNPs) showed potential in PG delivery and cancer treatments.

Endoscopic Grading, Radiological Grading and Clinical Features in Children with Chronic Adenoid Hypertrophy: A Correlational Study.

To obtain a correlation between endoscopic findings, radiological findings and clinical features in children with symptomatic Chronic Adenoid hypertrophy. A cross sectional study was conducted in 42 pediatric patients (3-14 years) who visited the Department of Otorhinolaryngology in a tertiary care centre from November 2019 to April 2021 (18 months). The patients were subjected to complete history taking; ENT examination, Rigid nasal endoscopic examination, a lateral X-ray nasopharynx were performed prior to surgery after obtaining consent from the parents of the patients. The endoscopic findings were assessed using ACE grading system and the X-ray nasopharynx was assessed using Adenoid- Nasopharyngeal ratio. A male predominance was noted with mouth breathing, snoring, nasal obstruction and recurrent rhinitis as common presentation. Grade 3 hypertrophy was the most common finding in X-ray Nasopharynx (Mean ANR-0.682). Children with Grade 3 adenoid hypertrophy with more than 50% choanal obstruction and Eustachian tube abutment in nasal endoscopy were noted to be the most symptomatic clinically. A positive correlation between reduced hearing (p value-0.004) and blocked ear sensation (p value- < 0.01) with eustachian tube abutment was noted. The children with more symptoms did not show higher-grade adenoid hypertrophy radiographically in our study. The adenoid- nasopharyngeal ratio on X-ray correlated with endoscopic grading of adenoid hypertrophy (p value-0.006) and degree of choanal obstruction (p value-0.003) but not with the abutment of the eustachian tube. The endoscopic grading correlated with clinical grading, but not the X-ray grading. Hence, endoscopic grading appears to be more accurate in assessing the adenoid size and endoscopic grading is nearer to clinical grading than X-ray grading. Though, the digital X-ray nasopharynx lateral view is a more convenient method, nasal endoscopy is the gold standard method to determine whether the adenoid hypertrophy is clinically significant or not.

Nanocarriers for ocular drug delivery: Recent advances and future opportunities.

Topical route of administration is very important and the most commonly used method of drug delivery for treatment of ocular diseases. However, due to unique anatomical and physiological barriers of eye, it is difficult to achieve the therapeutic concentration in the targeted tissue within the eye. To overcome the effect of these barriers in absorption and to provide targeted and sustained drug delivery, various advances have been made in developing safe and efficient drug delivery systems. Various formulation strategies for ocular drug delivery are used, like basic formulation techniques for improving availability of drugs, viscosity enhancers, and use of mucoadhesives for drug retention and penetration enhancers to promote drug transport to the eye. In this review, we present a summary of the current literature to understand the anatomical and physiological limitations in achieving adequate ocular bioavailability and targeted drug delivery of topically applied drugs and use of new techniques in formulating dosage forms in overcoming these limitations. The recent and future advances in nanocarrier-mediated drug delivery may have the potential to provide patient-friendly and noninvasive techniques for the treatment of diseases related to the anterior and posterior segments of the eye.

Incidence and Prevalence of Fungal Sinusitis in Cases of Chronic Rhinosinusitis.

To study the incidence and prevalence of fungal sinusitis and its variants in cases of chronic rhinosinusitis in department of ENT and Head and Neck surgery. The study group consisted of 100 patients of chronic rhinosinusitis attending the outpatient and inpatients in department of Otorhinolaryngology. History was taken and diagnostic nasal endoscopy was performed. Patients underwent endoscopic sinus surgery and systemic treatment when required. Pre surgery serum IgE and post-surgery Histopathology was sent. Out of 100 patients, Males > Females and median age was 45.50 years (range 34.25-59.25 years). On DNE, 88% had polyps with 88.1% males and 87.8% females in their respective groups. 47% had allergic mucin with 49.2% males and 43.9% females in their respective groups. 34% had discharge with 28.8% males and 41.5% females in their respective groups. 37% had fungal filaments with 37.3% males and 36.6% females in their respective groups. 26% had fungal sinusitis in our study among which 53.8% were males and 46.1% were females. Peak fungal sinusitis was in 3rd to 5th decade. Commonest organism isolated was Aspergillus. Serum IgE was higher in patients with fungal sinusitis and nasal polyposis. In conclusion, the proportion of patients with Fungal Sinusitis was 26% among 100 patients with chronic rhinosinusitis. We isolated Aspergillus as the predominant fungus followed by Biporalis and Mucorales genus. Serum IgE was higher in patients with fungal sinusitis and Nasal polyposis. Both immunocompromised and competent individuals were managed surgically and/or medically when required. Our study showed that early fungal sinusitis detection leads to better management practices and prevents its progression into more severe disease with complications.

Perspectives of colon-specific drug delivery in the management of morning symptoms of rheumatoid arthritis.

Rheumatoid arthritis is a chronic condition that is characterized by joint pain and inflammation. It is an autoimmune disorder in which the body tissues are erroneously attacked by the immune system of the host itself. It has been evident that rheumatoid arthritis symptoms follow a 24 h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning. Colon-specific drug delivery systems can be utilized in the formulations to be used in the treatment of rheumatoid arthritis. The colon-specific drug delivery system has shown promising results in the treatment of different diseases at the colonic site like Crohn's disease, ulcerative colitis, colon cancer, etc. The colon-specific drug delivery is capable of delivering the formulation at the predetermined location and predetermined time. The early morning symptoms of rheumatoid arthritis like pain and inflammation can be treated using the various approaches of the colon-specific drug delivery system because it will lead to patient compliance as the patient will not require administering the formulation immediately after waking up in the morning. This review also explains the immunological factors which may trigger rheumatoid arthritis in human beings. It further explores conventional approaches like pH-dependant, microorganisms-driven, pressure-controlled, and time-dependant formulations. By employing two or more conventional approaches given above the various novel approaches have been designed to eliminate the drawbacks of individual techniques.

Retrospective Analysis of Transnasal Endoscopic CSF Rhinorrhea Repair in a Tertiary Care Centre.

To analyse the outcome of transnasal endoscopic repair of CSF Rhinorrhea in a tertiary care centre. This is a retrospective study conducted on 81 patients who underwent CSF Rhinorrhea repair in a tertiary care hospital for a period of 11 years. Following confirmation of diagnosis using bio-chemical and radiological investigations, all patients underwent transnasal endoscopic repair of CSF Rhinorrhea using a multilayer graft. Patients were followed up for 6 months. The most common etiology in our study was spontaneous CSF rhinorrhea (60.49%) and subjects with BMI > 25.5 kg/m2 were more prone to it. Cribriform plate was found to be the most frequent site of leak in our study (58.02%), followed by fovea ethmoidalis (12.35%). Overall success rate was 96.30%. Transnasal endoscopic approach for cerebrospinal fluid rhinorrhea repair shows good success rate and also offers the advantages of better visualization and identification of site of leak, less complications, rapid postoperative recovery, and low recurrence rate. Transnasal endoscopic CSF Rhinorrhea repair has shown good results in terms of low recurrence rates and high patient satisfaction among other advantages. Hence this approach should be commonly used for CSF rhinorrhea repair by surgeons.

First report of Fusarium verticillioides causing Pokkah boeng disease on maize in India.

Maize is a widely grown cereal crop in India and ranks third to wheat and rice in production (https://iimr.icar.gov.in). During a field survey in Kharif season in 2018, foliar chlorosis at the base and middle of leaves, and twisted top symptoms were observed in 40-50 days old maize plants in Belagavi district, Karnataka, India. Again during Kharif season in 2021, similar symptoms were observed on commercial maize hybrids and sugarcane at Agricultural Research Station, Sankeshwar Karnataka. The symptoms resembled Pokkah boeng disease of sugarcane (Vishwakarma et al. 2013). Symptomatic sugarcane and maize leaves were sampled, surface sterilized with 1.0% sodium hypochlorite, and 70% ethanol, and transferred on Potato dextrose agar, incubated for 10 days at 27±1°C. Fungal growth initiated with white mycelium later turned to pinkish-white with hyaline spores. The morphological features and sporulation patterns of maize and sugarcane samples were similar (e-Xtra 1). Microconidia were formed in long chains and clusters with oval to club-shaped, 0-septate, monophialide-borne microspores. DNA from representative pure culture isolates was extracted using the CTAB protocol (Doyle and Doyle, 1990). The ITS region of r-DNA was amplified with ITS1/ITS4 primers and sequenced. BLAST analyses of sequences of maize and sugarcane culture isolates at NCBI database revealed 100% homology with Fusarium verticillioides MK264336 (Lin et al., 2016). PCR amplification with Fusarium verticilliodes specific primers VER1/VER2 (Mule et al., 2004) confirmed the organism. CBS-KNAW Fungal Biodiversity Centre's Fusarium MLST database also revealed over 98.89% homology with Fusarium verticilliodes (NRRL 46612). The fungal isolates were named Fusarium verticilliodes maize isolate SNK 01 (ON110289) and Fusarium verticilliodes sugarcane isolate SNK 01 (ON564879), and their sequences were deposited in the GenBank. To test pathogenicity, artificial inoculation using maize isolate SNK 01 and cross-inoculation of sugarcane isolate SNK 01 were done on ten maize plants by spraying a conidial suspension (2×106 conidia ml-1) on nonwounded leaves. The plants sprayed with sterile water were used as control. After ten days, typical Pokkah boeng symptoms were observed in the plants inoculated with both maize and sugarcane isolates. Diseased leaves turned pale yellowish-green with small brown spots and a chlorotic appearance, further, these developed into stripes (e-Xtra 2). Wrinkling of leaves was noticed followed by splitting and rotting. No symptoms were noticed in the water-treated control. The pathogens re-isolated from diseased plants inoculated with maize and sugarcane isolates were similar morphologically and identical to the original isolates, fulfilling Koch's postulates. Hitherto, Fusarium verticilliodes was known to cause post-flowering stalk rot in maize. However, this is the first report of Pokkah boeng disease on maize in India caused by F. verticillioides. Considering the economic value of the maize crop, this identification can help develop appropriate disease management strategies to control the disease. References Lee, S. B., et al. 1988. A rapid, high yield mini-prep method for isolation of total genomic DNA from fungi. Fungal Genet. Newsl. 35:23-24. Lin, Z., et al. 2016. Deciphering transcriptomic response of Fusarium verticillioides in relation to nitrogen availability and the development of sugarcane Pokkah boeng disease. Sci. Rep. 6, 29692. Mule, G., et al. 2004. A Species-Specific PCR assay based on the Calmodulin partial gene for identification of Fusarium verticillioides, F. proliferatum and F. subglutinans. European J. Plant Path. 110:495-502 Vishwakarma, S.K., et al. 2013. Pokkah Boeng: an emerging disease of sugarcane. J. Plant Pathol. Microb. 4(3):170. https://iimr.icar.gov.in. Director's desk, ICAR-Indian Institute of Maize Research. (Accessed September 8, 2022).

Serum Adenosine Deaminase Levels and Human Papillomavirus as Prognostic and Predictive Factors for Laryngeal and Pharyngeal Carcinomas.

Head and neck cancer is one of the most common cancers in the world, accounting for up to 30-40% malignancies in India. Research is always on the lookout for parameters that help in early diagnosis of such disease and to explore the possibility of discovering such parameters that would assist in management of the disease by its potential to predict and prognosticate the disease. To estimate serum ADA levels and to correlate with response to therapy and also to correlate between different clinical stages and serum ADA levels and to correlate HPV status to response to therapy. A prospective cohort study. 30 patients who were diagnosed with squamous cell carcinoma of the oropharynx, hypopharynx and larynx were considered in this study. The pre and post treatment values of serum ADA was estimated in these patients and the tumour was assessed for HPV status. The difference in the in the serum ADA levels before and after treatment was 9.982 which was statistically significant with a p value of < 0.001. HPV positive status and response to therapy in the form of recurrence shows a p value of 0.485 which is not statistically significant. Serum ADA level can be used as a parameter to assess the severity of the disease and the response to treatment in cases of carcinoma of the oropharynx, hypopharynx and larynx. HPV status of the disease has its limitation in prediction and prognosis of the disease.

Comparison of Elective Minimally Invasive with Conventional Surgical Tracheostomy in Adults.

Minimally invasive techniques were used for tracheostomy including small horizontal skin incision, limited soft tissue dissection and no suturing. A Retrospective analysis of case sheets of patients who underwent elective tracheostomy by the first and second authors at M S Ramaiah Hospitals in Bangalore between 1st May 2010 and 1st May 2015 was done to compare the result of elective conventional open surgical tracheostomy using midline vertical skin incision with minimally invasive tracheostomy using a short horizontal incision. No statistically significant difference in the peri and post operative complication rate was found. The patterns of intra and post operative complications reflected the choice of the surgical technique-the conventional technique had problems associated with wide dissection, whereas the minimally invasive technique had problems associated with limited exposure. Problems of wound gaping, emphysema and peristomal inflammation were reduced with minimally invasive technique with short horizontal skin incision although statistical difference could not be shown. There was also no statistically significant difference with either technique regards death and decannulation rates. Minimally invasive technique of elective open surgical tracheostomy was found to be as safe as conventional open surgical tracheostomy with midline vertical skin incision in the studied groups.

Ion activated in situ gel of gellan gum containing salbutamol sulphate for nasal administration.

Nasal delivery is the promising approach for rapid onset of action and avoids the first pass metabolism. The main aim of present study was to develop a novel mucoadhesive in situ gel of salbutamol sulphate using gellan gum and hydroxylpropyl methyl cellulose (HPMC) for nasal administration. The formulations were prepared so as to have gelation at physiological ion content after nasal administration. Developed formulations were evaluated for gelation, viscosity, drug content, in vitro mucoadhesion, in vitro drug release study, ex vivo permeation, and histopathology. Formulations showed pH in the range of nasal cavity and optimum viscosity for nasal administration. The mucoadhesive force depends upon concentration of HPMC and drug release was found to be 97.34% in 11h. The histopathology did not detect any damage during ex vivo permeation studies. Hence, in situ gel system of gellan gum may be a promising approach for nasal delivery of salbutamol sulphate for therapeutic improvement.

Development and optimization of multiparticulate drug delivery system of alfuzosin hydrochloride.

The purpose of present research was to develop and optimize sustained release floating pellets of alfuzosin hydrochloride which has narrow absorption window in proximal intestine to improve patient compliance and therapeutic efficacy in the treatment of benign prostatic hyperplasia. The system was designed to provide drug loaded pellets coated with three successive coatings over Celphere(®) (microcrystalline cellulose pellets) - drug layer, effervescent layer (HPMC and sodium bicarbonate) and gas entrapped polymeric membrane (Kollicoat(®) SR 30D). A 3(2) factorial design was employed with HPMC:sodium bicarbonate and Kollicoat(®) SR 30D concentration as independent variables while drug release and floating lag time were the dependent variables. Regression analysis was performed to identify best formulation conditions. Scanning electron microscopy was used to study pellet morphology. The floating ability and in vitro drug release of the system were dependent on amount of sodium bicarbonate layered onto pellets and coating level of Kollicoat(®) SR 30D.

In vivo evaluation of alginate microspheres of carvedilol for nasal delivery.

Mucoadhesive alginate microspheres of carvedilol (CRV) for nasal administration intended to avoid first pass metabolism and to improve bioavailability were prepared and evaluated. The microspheres were prepared by emulsification cross-linking method. Radiolabeling of CRV and its microspheres was performed by direct labeling with reduced technetium-99m ((99m) Tc). In vivo studies were performed on New Zealand white rabbits by administering the microspheres intranasally using monodose nasal insufflator. The radioactivity was measured in a well-type gamma scintillation counter. The noncompartmental pharmacokinetic analysis was performed. The pattern of deposition and clearance of the microspheres were evaluated using a radioactive tracer and the noninvasive technique of gamma scintigraphy. The clearance of alginate microsphere was compared with that of control lactose. The microspheres were nonaggregated, free flowing powders with spherical shape, and smooth surface. Pharmacokinetics study displayed an increase in area under the curve and hence in relative bioavailability when compared with intravenous administration of drug. The nasal bioavailability was 67.87% which indicates that nasal administration results in improved absorption of CRV. The results of gamma scintigraphy showed that the alginate microspheres had significantly reduced rates of clearance from the rabbit nasal cavity when compared with the control lactose.

Chitosan microspheres as a delivery system for nasal insufflation.

The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres for nasal delivery. The microspheres were prepared by emulsification-crosslinking method and evaluated for morphology, particle size, swelling index, in vitro mucoadhesion and delivery properties from Miat(®) nasal insufflator. The results showed that the microspheres were spherical in shape with smooth surfaces. The particle size of microspheres was found to be dependent on the concentration of the chitosan. The mean particle size was significantly increased when high concentration of chitosan was used. Aqueous to oil phase ratio, stirring rate and dioctyl sodium sulfosuccinate (DOSS) concentration also influenced the particle size distribution of the microspheres. It was found that, as stirring rate was increased, the size of the microspheres was decreased. The volume of glutaraldehyde and crosslinking time had very slight effect on particle size distribution. The % equilibrium water uptake of the microspheres was ranged from 124% to 232% and the mucoadhesive strength from 70.64±2.14 to 86.32±3.96%. The results of powder delivery from the device showed that, almost entire amount was delivered after three puffs. The images of the delivery sequences of microsphere powder clouds demonstrated that microspheres were delivered forming an elongated puff. The core of the clouds was homogeneous which can be expected to provide effective distribution pattern.

Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery.

The present research work was aimed at development and optimization of alginate mucoadhesive microspheres of carvedilol for nasal delivery to avoid first pass metabolism and to improve the therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared by a water-in-oil (w/o) emulsification technique. A 2(3) factorial design was employed with drug : polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size of the microspheres and in vitro mucoadhesion were the dependent variables. Regression analysis was performed to identify the best formulation conditions. Particle size was analysed by dynamic laser light diffraction technique and found to be in the range of 26.36-54.32 microm, which is favourable for intranasal absorption. The shape and surface characteristics were determined by scanning electron microscopy (SEM) which depicted the spherical nature and nearly smooth surfaces of the microspheres. The percentage encapsulation efficiency was found to be in the range between 36.62-56.18. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 69.25-85.28. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of carvedilol in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated non-Fickian or anomalous type of transport for the release of carvedilol from the microspheres.

Mucoadhesive microspheres: a promising tool in drug delivery.

Mucoadhesive polymers have recently gained interest among pharmaceutical scientists as a means of improving drug delivery by promoting the residence time and contact time of the dosage form with the mucous membranes. Mucoadhesion is the process whereby synthetic and natural polymers adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug will be released at the site for an extended period of time. Microspheres, in general, have the potential to be used for targeted and controlled release drug delivery; however, coupling of mucoadhesive properties to microspheres has additional advantages like, a much more intimate contact with the mucus layer, efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio. The present review describes the potential applications of mucoadhesive microspheres as a novel carrier system to improve drug delivery by various routes of administration like buccal, oral, nasal, ocular, vaginal and rectal, either for systemic or for local effects. The mucoadhesive polymers, methods of preparation of microspheres and their in vitro and in vivo evaluation are also described.