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Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
Fulltext Smell Outcome and Seropositivity Titre in Post-COVID-19 Patients

Harminder Singh SK, Husain S, Wan Hamizan AK, Zahedi FD, Othman SN, Zainol Rashid Z

ORL J Otorhinolaryngol Relat Spec, 2023;85(6):305-311.
PMID: 37473733 DOI: 10.1159/000531222

INTRODUCTION: The aims of the study were to perform an olfactory assessment on patients active and post-COVID-19 using the culturally adapted Malaysian version Sniffin' Sticks identification smell test (mSS-SIT), to evaluate the patient olfactory outcome using a Malay short version of the Questionnaire of Olfactory Disorders-Negative Statements (msQOD-NS), as well as to evaluate seropositive titre (IgG) response using automated serology method.
METHODS: Score for mSS-SIT was performed during the hospitalization, when patients had tested positive for SARS-CoV-2 (during COVID-19), and repeated after they had tested negative (after COVID-19). Also, each patient completed msQOD-NS and serology SARS-CoV-2 antibodies blood test was evaluated.
RESULTS: During COVID-19, 2 of our patients were anosmia (6.5%), 22 (70.9%) were hyposmia, and 7 (22.6%) were normosmia. We repeated mSS-SIT on these same patients after COVID-19, and none of these subjects were hyposmia or anosmia, as they achieved a score >12. All our patients had scored 21 using msQOD-NS, meaning no impact on quality of life as they had regained their normal olfactory function. In this study also, we obtained no correlation between smell test and seropositivity titre COVID-19, and antibody levels gradually decreased over time till 6 months and remained stable up to 12 months.
CONCLUSION: From this study, we know full recovery of the sense of smell can be expected post-COVID-19 infection and COVID-19 antibody persists in the body up to 12 months of infection.
A new era in oxygen therapeutics? From perfluorocarbon systems to haemoglobin-based oxygen carriers

Charbe NB, Castillo F, Tambuwala MM, Prasher P, Chellappan DK, Carreño A, et al.

Blood Rev, 2022 Jan 21.
PMID: 35094845 DOI: 10.1016/j.blre.2022.100927

Blood transfusion is the key to life in case of traumatic emergencies, surgeries and in several pathological conditions. An important goal of whole blood or red blood cell transfusion is the fast delivery of oxygen to vital organs and restoration of circulation volume. Whole blood or red blood cell transfusion has several limitations. Free haemoglobin not only loses its tetrameric configuration and extracts via the kidney leading to nephrotoxicity but also scavenges nitric oxide (NO), leading to vasoconstriction and hypertension. PFC based formulations transport oxygen in vivo, the contribution in terms of clinical outcome is challenging. The oxygen-carrying capacity is not the only criterion for the successful development of haemoglobin-based oxygen carriers (HBOCs). This review is a bird's eye view on the present state of the PFCs and HBOCs in which we analyzed the current modifications made or which are underway in development, their promises, and hurdles in clinical implementation.
Fulltext [Combined spinal-epidural analgesia in labour: its effects on delivery outcome]

Singh SK, Yahya N, Misiran K, Masdar A, Nor NM, Yee LC

Rev Bras Anestesiol, 2016 May-Jun;66(3):259-64.
PMID: 26993410 DOI: 10.1016/j.bjan.2014.09.009

Combined spinal-epidural (CSE) has become an increasingly popular alternative to traditional labour epidural due to its rapid onset and reliable analgesia provided. This was a prospective, convenient sampling study to determine the effects of CSE analgesia on labour outcome.
Fulltext Combined spinal-epidural analgesia in labour: its effects on delivery outcome

Singh SK, Yahya N, Misiran K, Masdar A, Nor NM, Yee LC

Braz J Anesthesiol, 2016 May-Jun;66(3):259-64.
PMID: 27108822 DOI: 10.1016/j.bjane.2014.09.006

BACKGROUND AND OBJECTIVES: Combined spinal-epidural (CSE) has become an increasingly popular alternative to traditional labour epidural due to its rapid onset and reliable analgesia provided. This was a prospective, convenient sampling study to determine the effects of CSE analgesia on labour outcome.

METHODS: One hundred and ten healthy primigravida parturients with a singleton pregnancy of ≥37 weeks gestation and in the active phase of labour were studied. They were enrolled to the CSE (n=55) or Non-CSE (n=55) group based on whether they consented to CSE analgesia. Non-CSE parturients were offered other methods of labour analgesia. The duration of the first and second stage of labour, rate of instrumental vaginal delivery and emergency cesarean section, and Apgar scores were compared.

RESULTS: The mean duration of the first and second stage of labour was not significantly different between both groups. Instrumental delivery rates between the groups were not significantly different (CSE group, 11% versus Non-CSE group, 16%). The slightly higher incidence of cesarean section in the CSE group (16% versus 15% in the Non-CSE group) was not statistically significant. Neonatal outcome in terms of Apgar score of less than 7 at 1 and 5min was similar in both groups.

CONCLUSION: There were no significant differences in the duration of labour, rate of instrumental vaginal delivery and emergency cesarean section, and neonatal outcome in parturients who received compared to those who did not receive CSE for labour analgesia.
Fulltext The Urological Association of Asia clinical guideline for urinary stone disease

Taguchi K, Cho SY, Ng AC, Usawachintachit M, Tan YK, Deng YL, et al.

Int J Urol, 2019 07;26(7):688-709.
PMID: 31016804 DOI: 10.1111/iju.13957

The Urological Association of Asia, consisting of 25 member associations and one affiliated member since its foundation in 1990, has planned to develop Asian guidelines for all urological fields. The field of stone diseases is the third of its guideline projects. Because of the different climates, and social, economic and ethnic environments, the clinical practice for urinary stone diseases widely varies among the Asian countries. The committee members of the Urological Association of Asia on the clinical guidelines for urinary stone disease carried out a surveillance study to better understand the diversity of the treatment strategy among different regions and subsequent systematic literature review through PubMed and MEDLINE database between 1966 and 2017. Levels of evidence and grades of recommendation for each management were decided according to the relevant strategy. Each clinical question and answer were thoroughly reviewed and discussed by all committee members and their colleagues, with suggestions from expert representatives of the American Urological Association and European Association of Urology. However, we focused on the pragmatic care of patients and our own evidence throughout Asia, which included recent surgical trends, such as miniaturized percutaneous nephrolithotomy and endoscopic combined intrarenal surgery. This guideline covers all fields of stone diseases, from etiology to recurrence prevention. Here, we present a short summary of the first version of the guideline - consisting 43 clinical questions - and overview its key practical issues.
Overcoming hydrolytic degradation challenges in topical delivery: non-aqueous nano-emulsions

Kadukkattil Ramanunny A, Singh SK, Wadhwa S, Gulati M, Kapoor B, Khursheed R, et al.

Expert Opin Drug Deliv, 2022 Jan;19(1):23-45.
PMID: 34913772 DOI: 10.1080/17425247.2022.2019218

INTRODUCTION: Non-aqueous nano-emulsions (NANEs) are colloidal lipid-based dispersions with nano-sized droplets formed by mixing two immiscible phases, none of which happens to be an aqueous phase. Their ability to incorporate water and oxygen sensitive drugs without any susceptibility to degradation makes them the optimum dosage form for such candidates. In NANEs, polar liquids or polyols replace the aqueous phase while surfactants remain same as used in conventional emulsions. They are a part of the nano-emulsion family albeit with substantial difference in composition and application.
AREAS COVERED: The present review provides a brief insight into the strategies of loading water-sensitive drugs into NANEs. Further advancement in these anhydrous systems with the use of solid particulate surfactants in the form of Pickering emulsions is also discussed.
EXPERT OPINION: NANEs offer a unique platform for delivering water-sensitive drugs by loading them in anhydrous formulation. The biggest advantage of NANEs vis-à-vis the other nano-cargos is that they can also be prepared without using equipment-intensive techniques. However, the use of NANEs in drug delivery is quite limited. Looking at the small number of studies available in this direction, a need for further research in this field is required to explore this delivery system further.
Prediction of meteorological drought and standardized precipitation index based on the random forest (RF), random tree (RT), and Gaussian process regression (GPR) models

Elbeltagi A, Pande CB, Kumar M, Tolche AD, Singh SK, Kumar A, et al.

Environ Sci Pollut Res Int, 2023 Mar;30(15):43183-43202.
PMID: 36648725 DOI: 10.1007/s11356-023-25221-3

Agriculture, meteorological, and hydrological drought is a natural hazard which affects ecosystems in the central India of Maharashtra state. Due to limited historical data for drought monitoring and forecasting available in the central India of Maharashtra state, implementing machine learning (ML) algorithms could allow for the prediction of future drought events. In this paper, we have focused on the prediction accuracy of meteorological drought in the semi-arid region based on the standardized precipitation index (SPI) using the random forest (RF), random tree (RT), and Gaussian process regression (GPR-PUK kernel) models. A different combination of machine learning models and variables has been performed for the forecasting of metrological drought based on the SPI-6 and 12 months. Models were developed using monthly rainfall data for the period of 2000-2019 at two meteorological stations, namely, Karanjali and Gangawdi, each representing a geographical region of Upper Godavari river basin area in the central India of Maharashtra state which frequently experiences droughts. Historical data from the SPI from 2000 to 2013 was processed to train the model into machine learning model, and the rest of the 2014 to 2019-year data were used for testing to forecast the SPI and metrological drought. The mean square error (MSE), root mean square error (RMSE), adjusted R2, Mallows' (Cp), Akaike's (AIC), Schwarz's (SBC), and Amemiya's PC were used to identify the best combination input model and best subregression analysis for both stations of SPI-6 and 12. The correlation coefficient ([Formula: see text]), mean absolute error (MAE), root mean square error (RMSE), relative absolute error (RAE), and root relative squared error (RRSE) were used to perform evaluation for SPI-6 and 12 months of both stations with RF, RT, and GPR-PUK kernel models during the training and testing scenarios. The results during testing phase revealed that the RF was found as the best model in forecasting droughts with values of [Formula: see text], MAE, RMSE, RAE (%), and RRSE (%) being 0.856, 0.551, 0.718, 74.778, and 54.019, respectively, for SPI-6 while 0.961, 0.361, 0.538, 34.926, and 28.262, respectively, for SPI-12 scales at Gangawdi station. Further, the respective values of evaluators at Karanjali station were 0.913 and 0.966, 0.541 and 0.386, 0.604 and 0.589, 52.592 and 36.959, and 42.315 and 31.394 for PUK kernel and RT models, respectively, during SPI-6 and SPI-12. Machine learning models are potential drought warning techniques because they take less time, have fewer inputs, and are less sophisticated than dynamic or scientific models.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Educational intervention on delirium assessment using confusion assessment method-ICU (CAM-ICU) in a general intensive care unit

Ramoo V, Abu H, Rai V, Surat Singh SK, Baharudin AA, Danaee M, et al.

J Clin Nurs, 2018 Nov;27(21-22):4028-4039.
PMID: 29775510 DOI: 10.1111/jocn.14525

AIMS AND OBJECTIVES: To assess intensive care unit nurses' knowledge of intensive care unit delirium and delirium assessment before and after an educational intervention. In addition, nurses' perception on the usefulness of a delirium assessment tool and barriers against delirium assessment were assessed as secondary objectives.
BACKGROUND: Early identification of delirium in intensive care units is crucial for patient care. Hence, nurses require adequate knowledge to enable appropriate evaluation of delirium using standardised practice and assessment tools.
DESIGN: This study, performed in Malaysia, used a single-group pretest-posttest study design to assess the effect of educational interventions and hands-on practices on nurses' knowledge of intensive care unit delirium and delirium assessment.
METHODS: Sixty-one nurses participated in educational intervention sessions, including classroom learning, demonstrations and hands-on practices on the Confusion Assessment Method-Intensive Care Unit. Data were collected using self-administered questionnaires for the pre- and postintervention assessments. Analysis to determine the effect of the educational intervention consisted of the repeated-measures analysis of covariance.
RESULTS: There were significant differences in the knowledge scores pre- and postintervention, after controlling for demographic characteristics. The two most common perceived barriers to the adoption of the intensive care unit delirium assessment tool were "physicians did not use nurses' delirium assessment in decision-making" and "difficult to interpret delirium in intubated patients".
CONCLUSIONS: Educational intervention and hands-on practices increased nurses' knowledge of delirium assessment. Teaching and interprofessional involvements are essential for a successful implementation of intensive care unit delirium assessment practice.
RELEVANCE TO CLINICAL PRACTICE: This study supports existing evidences, indicating that education and training could increase nurses' knowledge of delirium and delirium assessment. Improving nurses' knowledge could potentially lead to better delirium management practice and improve ICU patient care. Thus, continuous efforts to improve and sustain nurses' knowledge become relevant in ICU settings.
Pangolin Indexing System: implications in forensic surveillance of large seizures

Singh A, Priyambada P, Jabin G, Singh SK, Joshi BD, Venkatraman C, et al.

Int J Legal Med, 2020 Sep;134(5):1613-1618.
PMID: 32621146 DOI: 10.1007/s00414-020-02362-5

Demand for pangolin scales in East Asia has increased dramatically in the past two decades, raising concern to the pangolin survival and bringing them to the brink of local extinction. Enumerating the number of individuals from the seized pangolin scales primarily goes undocumented, mostly due to the unavailability of the appropriate methods. In this study, we developed a Pangolin Indexing System, a multi-locus STR panel of eight dinucleotide microsatellites that showed promising results in individualization and assignment of scales into Chinese and Indian pangolins. The combined power of exclusion was 0.83 and 0.99 for Chinese and Indian pangolin. The select panel of eight polymorphic STRs exhibited the cumulative probability of identity 3.7 × 10-9 for Indian pangolin and 3.6 × 10-7 for Chinese pangolin and identified 51 unique genotypes from the 74 scales selected from the four pangolin seizures. The study demonstrated the first report of cross-species validation of STRs developed from Malayan pangolin to Indian pangolin and showed the potential application of Pangolin Indexing System in screening of large seizures through DNA profiling from the scales of Indian and Chinese pangolin.
Fulltext Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies

Rathore C, Hemrajani C, Sharma AK, Gupta PK, Jha NK, Aljabali AAA, et al.

Drug Deliv Transl Res, 2023 Jan;13(1):292-307.
PMID: 35831776 DOI: 10.1007/s13346-022-01193-8

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (
Fulltext CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis

Bhat AA, Gupta G, Dahiya R, Thapa R, Gahtori A, Shahwan M, et al.

Noncoding RNA Res, 2024 Jun;9(2):277-287.
PMID: 38505309 DOI: 10.1016/j.ncrna.2024.01.013

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-β (TGF-β) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-β pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-β signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-β modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-β signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-β is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-β signalling landscape.
Combination therapy of vanillic acid and oxaliplatin co-loaded in polysaccharide based functionalized polymeric micelles could offer effective treatment for colon cancer: A hypothesis

Kaur J, Gulati M, Gowthamarajan K, Vishwas S, Kumar Chellappan D, Gupta G, et al.

Med Hypotheses, 2021 Sep 14;156:110679.
PMID: 34555619 DOI: 10.1016/j.mehy.2021.110679

Colon cancer is characterised by the persistent change in bowel habits due to the formation of polyps (cancerous) in the inner lining of the colon. Clinically, there are several anticancer drugs available to treat colon cancer. Oxaliplatin (third generation platinum drug) is widely prescribed anticancer drug due to its broad range anticancer properties and low toxicities over cisplatin and carboplatin. Currently, use of oxaliplatin as adjuvant chemotherapy represents a standard care for the treatment of advanced colon cancer. Despite this, its rapid degradation in systemic circulations upon administration, lack of tumor specificity, and low bioavailability limits its anticancer potential. On the other hand, vanillic acid (VA) has shown anticancer potential in colon cancer by targeting mTOR/Ras pathway, HIF-1α inhibition, NF-ĸB, and Nrf2 that regulate cell growth, cell survival, proliferation and adaptation to cancer microenvironment. Normal oral delivery of these two drugs offers non-specific drug release in gastrointestinal tract that leads to unwanted toxicity and very less amount of drug become available for colonic site. Therefore, loading of these two drugs in polysaccharide based functionalized polymeric micelles (FPMs) can offer selective targeting at colonic site and could offer better therapeutic efficacy at much lesser doses of drugs. Therefore, a new hypothesis has been proposed that the combination of vanillic acid with oxaliplatin co-loaded in FPMs could provide colon targeting ability with enhanced potency and safety profile by targeting multiple pathways than current adjuvant chemotherapies available in the market for the treatment of colon cancer.
Novel Nanostructured Lipid Carriers Co-Loaded with Mesalamine and Curcumin: Formulation, Optimization and In Vitro Evaluation

Awasthi A, Kumar B, Gulati M, Vishwas S, Corrie L, Kaur J, et al.

Pharm Res, 2022 Nov;39(11):2817-2829.
PMID: 36195824 DOI: 10.1007/s11095-022-03401-z

PURPOSE: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs).
METHODS: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined.
RESULTS: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed.
CONCLUSION: The outcomes of study deciphered successful formulation of Mes-Cur NLCs.
Multifaceted role of synbiotics as nutraceuticals, therapeutics and carrier for drug delivery

Khursheed R, Gulati M, Wadhwa S, Vishwas S, Sharma DS, Corrie L, et al.

Chem Biol Interact, 2022 Dec 01;368:110223.
PMID: 36283466 DOI: 10.1016/j.cbi.2022.110223

Synbiotics, are a combination of probiotics and prebiotics. They play an important role in metabolizing different nutritional substrates and thus helps in the maintenance of human health. Any disbalance in the gut microflora, known as dysbiosis, is known to lead to a number of diseased conditions. It can be reverted by the administration of synbiotics. Present review highlights various mechanistic pathways through which synbiotics act as therapeutics. The dual role of synbiotics as nutraceutical and excipient in developing oral formulations are entailed with case studies. The findings entailed that there exist numerous studies on prebiotics as well as probiotics have been carried out to show their effects in several diseases. However, the concept of combining together them for prevention and treatment of various pathological conditions accruing from dysbiosis is relatively new. Synbiotics, however, face challenge of low stability during their sojourn in the GIT, which is generally overcome by various encapsulation techniques. Various studies also showed potential role of synbiotics in drug delivery. However, it is an emerging area and lacks clinical correlation. It is important to focus on clinical trials of formulations wherein synbiotics have been used as therapeutic moiety as well as pharmaceutical carrier for treating various diseases.
Harnessing the dual role of polysaccharides in treating gastrointestinal diseases: As therapeutics and polymers for drug delivery

Corrie L, Gulati M, Awasthi A, Vishwas S, Kaur J, Khursheed R, et al.

Chem Biol Interact, 2022 Dec 01;368:110238.
PMID: 36306865 DOI: 10.1016/j.cbi.2022.110238

Polysaccharides (PS) represent a broad class of polymer-based compounds that have been extensively researched as therapeutics and excipients for drug delivery. As pharmaceutical carriers, PS have mostly found their use as adsorbents, suspending agents, as well as cross-linking agents for various formulations such as liposomes, nanoparticles, nanoemulsions, nano lipid carriers, microspheres etc. This is due to inherent properties of PS such as porosity, steric stability and swellability, insolubility in pH. There have been emerging reports on the use of PS as therapeutic agent due to its anti-inflammatory and anti-oxidative properties for various diseases. In particular, for Crohn's disease, ulcerative colitis and inflammatory bowel disease. However, determining the dosage, treatment duration and effective technology transfer of these therapeutic moieties have not occurred. This is due to the fact that PS are still at a nascent stage of development to a full proof therapy for a particular disease. Recently, a combination of polysaccharide which act as a prebiotic and a probiotic have been used as a combination to treat various intestinal and colorectal (CRC) related diseases. This has proven to be beneficial, has shown good in vivo correlation and is well reported. The present review entails a detailed description on the role of PS used as a therapeutic agent and as a formulation pertaining to gastrointestinal diseases.
Fulltext Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment

Corrie L, Kaur J, Awasthi A, Vishwas S, Gulati M, Saini S, et al.

Pharmaceutics, 2022 Nov 06;14(11).
PMID: 36365213 DOI: 10.3390/pharmaceutics14112395

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.
Fulltext Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives

Chaitanya MVNL, Ramanunny AK, Babu MR, Gulati M, Vishwas S, Singh TG, et al.

Pharmaceutics, 2022 Nov 07;14(11).
PMID: 36365218 DOI: 10.3390/pharmaceutics14112401

Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from its dietary and therapeutic values, RA is an important anticancer phytochemical owing to its multi-targeting anticancer mechanism. These properties provide a scope for RA's therapeutic uses beyond its traditional use as a dietary source. However, its oral bioavailability is limited due to its poor solubility and permeability. This impedes its efficacy in treating cancer. Indeed, in recent years, tremendous efforts have been put towards the development of nanoformulations of RA for treating cancer. However, this research is in its initial stage as bringing a nanoparticle into the market itself is associated with many issues such as stability, toxicity, and scale-up issues. Considering these pitfalls during formulation development and overcoming them would surely provide a new face to RA as a nanomedicine to treat cancer. A literature search was conducted to systematically review the various biological sources, extraction techniques, and anticancer mechanisms through which RA showed multiple therapeutic effects. Various nanocarriers of RA pertaining to its anticancer activity are also discussed in this review.
Fulltext Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

Harish V, Tewari D, Mohd S, Govindaiah P, Babu MR, Kumar R, et al.

Pharmaceutics, 2022 Nov 07;14(11).
PMID: 36365221 DOI: 10.3390/pharmaceutics14112403

Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box-Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (-12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in Cmax (1.07-folds), AUC0-t (4.70-folds), t1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.

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