Enhancing Curcumin's therapeutic potential in cancer treatment through ultrasound mediated liposomal delivery.

Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin's anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm2 power density with 0.6 × 107 microbubbles/mL. Furthermore, the study delved into curcumin liposomes' cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.

Production of Targeted Estrone Liposomes Using a Herringbone Micromixer.

Liposomes are spherical vesicles formed from bilayer lipid membranes that are extensively used in targeted drug delivery as nanocarriers to deliver therapeutic reagents to specific tissues and organs in the body. Recently, we have reported using estrone as an endogenous ligand on doxorubicin-encapsulating liposomes to target estrogen receptor (E.R.)-positive breast cancer cells. Estrone liposomes were synthesized using the thin-film hydration method, which is a long, arduous, and multistep process. Here, we report using a herringbone micromixer to synthesize estrone liposomes in a simple and rapid manner. A solvent stream containing the lipids was mixed with a stream of phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhanced the mixing of the two streams. The small scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters on liposome size, such as the ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations, and solvent type, were investigated. Using this commercially available chip, we obtained liposomes with a radius of 66.1 ± 11.2 nm (mean ± standard deviation) and a polydispersity of 22% in less than 15 minutes compared to a total of ~11 hours using conventional techniques. Calcein was encapsulated inside the prepared liposomes as a model drug and was released by applying ultrasound at different powers. The size of the prepared liposomes was stable over a period of one month. Overall, using microfluidics to synthesize Estrone-liposomes simplified the procedure considerably and improved the reproducibility of the resulting liposomes.

The rare genetic disease research landscape in India.

I am delighted to see this special issue on 'The Rare Genetic Disease Research Landscape in India'' by the Journal of Biosciences, published by the Indian Academy of Sciences in collaboration with Springer Nature. It is the first time that a mainstream biology journal has decided to publish a whole issue on rare genetic disorders. I congratulate the editorial board of the Journal of Biosciences for their timely support to encourage research in this area. I also believe that this issue will increase awareness about rare genetic diseases research and encourage many in India to enter the field.

Effect of phospholipid head group on ultrasound-triggered drug release and cellular uptake of immunoliposomes.

Liposomes are the most successful nanoparticles used to date to load and deliver chemotherapeutic agents to cancer cells. They are nano-sized vesicles made up of phospholipids, and targeting moieties can be added to their surfaces for the active targeting of specific tumors. Furthermore, Ultrasound can be used to trigger the release of the loaded drugs by disturbing their phospholipid bilayer structure. In this study, we have prepared pegylated liposomes using four types of phospholipids with similar saturated hydrocarbon tails including a phospholipid with no head group attached to the phosphate head (DPPA) and three other phospholipids with different head groups attached to their phosphate heads (DPPC, DPPE and DPPG). The prepared liposomes were conjugated to the monoclonal antibody trastuzumab (TRA) to target the human epidermal growth factor receptor 2 (HER2) overexpressed on HER2-positive cancer cells (HER2+). We have compared the response of the different formulations of liposomes when triggered with low-frequency ultrasound (LFUS) and their cellular uptake by the cancer cells. The results showed that the different formulations had similar size, polydispersity, and stability. TRA-conjugated DPPC liposomes showed the highest sensitivity to LFUS. On the other hand, incubating the cancer cells with TRA-conjugated DPPA liposomes triggered with LFUS showed the highest uptake of the loaded calcein by the HER2+ cells.

Service-learning under COVID-19: A scoping review of the challenges and opportunities for practicing service-learning in the 'New Normal'.

Service-learning collaborations have the potential to effectively respond to community needs, students' needs, and institutional priorities. However, natural and man-made crises oftentimes throw these arrangements into disarray. The coronavirus (COVID-19) is one such significant crisis that continues to challenge service-learning collaborations worldwide. Based on a systematic scoping review of scholarship on service-learning programs conducted during COVID-19, this study aimed to explore thematic similarities and differences between them, elucidating key observations and insights for future action. Overall, findings from 13 peer-reviewed articles indicated that, although not immune to the wide-ranging adverse effects of COVID-19, service-learning has proven itself to be an effective responsive pedagogy in times of crisis.

A latent profile analysis of child maltreatment among at-risk youth gang members: Associations with violent delinquency, non-violent delinquency, and gang organizational structures.

BACKGROUND: The relationship between child maltreatment and later delinquency is an enduring concern worldwide. However, the maltreatment-delinquency relationship is relatively underexplored in youth gang populations. Consequently, to date, studies have not examined typologies of maltreatment and their associations with violent delinquency, non-violent delinquency, and gang organizational structures. OBJECTIVE: First, to identify the characteristics of subgroups of youth gang members who varied in abuse type and severity within type. Second, to determine in what ways the profiles differed in terms of gang organizational structures, violent delinquency, and non-violent delinquency. PARTICIPANTS AND SETTINGS: A sample of 161 youth gang members (mean age: 16.8; range: 12-24) were recruited and surveyed by outreach social workers in Hong Kong. METHODS: Latent profile analysis was first used to examine heterogeneity in victimization experiences (physical abuse, sexual abuse, emotional abuse, and neglect). Thereafter, non-parametric tests and post-hoc analyses were conducted to examine associations between the yielded typologies of maltreatment and gang organizational structures, violent delinquency, and non-violent delinquency. RESULTS: Poly-victimization was prevalent in the sample, with 148 respondents (91.9 %) reporting at least two types of past abuses. Three profiles of maltreatment emerged, varying in abuse types and severity within types: 'Minimally maltreated', 'Moderately maltreated, except sexual abuse', and 'Severely maltreated'. In comparison to the 'Minimal' maltreatment profile, the 'Moderate' and 'Severe' profiles were associated with greater delinquent behaviors and being in gangs that encouraged congregate illegal behaviors. CONCLUSIONS: There was a relationship between typologies of maltreatment and gang organizational structures, violent delinquency, and non-violent delinquency in the sample of youth gang members. Implications for practice and future research are discussed.

Comparison of regional versus global growth charts for the classification of small-for-gestational age neonates.

OBJECTIVE: To compare the performance of regional versus global charts for identifying small-for-gestational age (SGA) neonates with short-term adverse outcomes. DESIGN: Prospective cohort study. SETTING: Level-3 neonatal unit in India. PATIENTS: Neonates were categorised into SGA and appropriate-for-gestational age (AGA; 10th-90th centile) using four charts, namely, the AIIMS, Lubchenco, Fenton and Intergrowth 21st charts. They were followed up for adverse outcomes until 28 days. OUTCOMES: We evaluated the (1) burden of SGA, (2) sensitivity and diagnostic OR (DOR), (3) relative risk (RR) and number needed to screen (NNS) to detect adverse outcomes in SGA versus 'optimal' AGA (50th-90th centile) and (4) RR of morbidities in 'additional SGA' (ie, classified as SGA by others but not by AIIMS chart). RESULTS: Among 1367 neonates, 19.6%, 4.5% and 12.5% were classified as SGA by Intergrowth 21st, AIIMS and Lubchenco charts, respectively. Intergrowth 21st had the highest sensitivity (39.1%) but the least DOR (2.6) to detect adverse outcomes; AIIMS chart had low sensitivity (19.3%) but higher DOR (4.3). RR and NNS were 3.7 and 14; 4.4 and 7; 4.0 and 8; 3.6 and 10 with Intergrowth 21st, AIIMS, Lubchenco and Fenton charts, respectively. 'Additional SGA' identified by Intergrowth 21st had lower risk of adverse outcomes than SGA identified by both the charts (RR 0.39; 95% CI 0.19 to 0.82). CONCLUSIONS: Compared with AIIMS and Lubchenco charts, Intergrowth 21st runs the risk of overdiagnosing SGA neonates who may not be at a higher risk of short-term morbidities.

Serum Trace Elements in Children with Well-Controlled and Drug Refractory Epilepsy Compared to Controls: An Observational Study.

Background: Trace elements have been implicated in pathogenesis of epilepsy. Studies till date have shown altered levels of serum trace elements in children with epilepsy. Objective: The objective of the current was to estimate serum levels of trace elements in children with well-controlled and drug refractory epilepsy and compare it with controls. Methodology: In a tertiary care teaching hospital of North India, serum selenium, copper, zinc, and iron were estimated in well-controlled and drug refractory epileptic children aged 2-12 years and compared with age and gender matched controls. Results: A total of 106 children with epilepsy (55 drug refractory and 51 well controlled) and 52 age and gender matched controls were included in the study. Serum selenium and copper were significantly decreased in cases compared to controls. After classifying epilepsy into well-controlled and drug refractory cases, only in the latter the significant difference for serum selenium and copper levels remained compared to controls. Additionally, in the drug refractory cases, serum iron levels were significantly reduced compared to controls. Conclusions: Serum trace elements are altered in children with epilepsy (more so in the drug refractory group) compared to controls. Monitoring of serum trace elements in children with epilepsy should be considered. Up to one-third of epilepsy is drug refractory of which only another third are amenable to surgery. It is worth investigating the therapeutic potential of altered micronutrient status in these patients.

Short-term neurodevelopment and growth outcomes of very and moderate preterm Indian infants.

OBJECTIVE: To study the growth and neurodevelopmental outcome of very and moderate preterm infants (VMPT) compared to term appropriate-for-age (term AGA) infants at 18-months corrected age. METHODS: This prospective cohort study enrolled consecutively born 212 VMPT infants and 250 term AGA controls delivered during study period. OUTCOME MEASURES: Major neurodevelopmental impairment (NDI) defined as any one of cerebral palsy, motor (MoDQ) or mental developmental quotient (MoDQ) <70 on Developmental Assessment Scale for Indian infants, visual or hearing impairment, or epilepsy, and growth outcomes. RESULTS: Among 195 VMPT and 240 term AGA infants who completed follow-up, the frequency of major NDI was 12.8% and 2.5% respectively (RR 5.1; 95% CI [2.13-12.19]). Major NDI was higher among infants <28 weeks gestation (39%) and birthweight <1000 grams (27%). A quarter of VMPT infants exhibited wasting and 18% stunting than 7% each among controls. CONCLUSION: VMPT infants had a higher frequency of major NDI and growth failure at 18-months.

Hybrid liposome/metal-organic framework as a promising dual-responsive nanocarriers for anticancer drug delivery.

In this work, liposome-coated iron (III) benzene-1,3,5-tricarboxylate (Fe-BTC) metal-organic framework is examined as a promising pH/Ultrasound dual-responsive nanocarriers for doxorubicin (DOX) delivery. The successful coating of the MOF particles (Lip-Fe-BTC) with the phospholipid bilayer (PBL) was established by direct fusion into the synthesized liposomes. The liposome coating was verified using several techniques, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The DLS measurements showed an increase in the average particle diameter of liposomes from 150 nm to 163.1 nm for Lip-Fe-BTC particles. The Fe-BTC particles had the highest average particle diameter (287.3 nm). These results demonstrated that the PBL reduced the aggregation of the particles and improved their dispersity in the release medium. The TGA results demonstrated the MOF's excellent thermal stability. Furthermore, the nanocarrier's loading efficiency and capacity were determined to be ~90% and ~13.5 wt%, respectively. The in-vitro DOX release experiments demonstrated that the DOX-loaded Fe-BTC and liposome-coated Fe-BTC particles showed good pH and US dual-responsive capability, making them promising nanocarriers for drug delivery. The application of US enhanced DOX release from both Fe-BTC and liposome-coated Fe-BTC. In the case of Fe-BTC-DOX particles, the application of US enhanced the DOX release to around 38% and 67%, at pH levels of 7.4 and 5.3, respectively. Similarly, DOX release from the Lip-Fe-BTC-DOX particles reached ~35% and ~53%, at pH levels of 7.4 and 5.3, respectively. The MTT assay showed the biocompatibility and low cytotoxicity of these nanocarriers below 100 µg/ml.

Ultrasound-sensitive cRGD-modified liposomes as a novel drug delivery system.

Targeted liposomes enable the delivery of encapsulated chemotherapeutics to tumours by targeting specific receptors overexpressed on the surfaces of cancer cells; this helps in reducing the systemic side effects associated with the cytotoxic agents. Upon reaching the targeted site, these liposomes can be triggered to release their payloads using internal or external triggers. In this study, we investigate the use of low-frequency ultrasound as an external modality to trigger the release of a model drug (calcein) from non-targeted and targeted pegylated liposomes modified with cyclic arginine-glycine-aspartate (cRGD). Liposomes were exposed to sonication at 20-kHz using three different power densities (6.2, 9, and 10 mW/cm2). Our results showed that increasing the power density increased calcein release from the sonicated liposomes. Moreover, cRGD conjugation to the surface of the liposomes rendered cRGD-liposomes more susceptible to ultrasound compared to the non-targeted liposomes. cRGD conjugation was also found to increase cellular uptake of calcein by human colorectal carcinoma (HCT116) cells which were further enhanced following sonicating the cells with low-frequency ultrasound (LFUS).

Associations among Bullying Victimization, Family Dysfunction, Negative Affect, and Bullying Perpetration in Macanese Adolescents.

Bullying has become one of the most significant problem behaviors that school-aged adolescents face. The current study examines the strain-delinquency relationship by employing General Strain Theory as a guiding framework. "Strain" was operationalized as bullying victimization and family dysfunction, "delinquency" was operationalized as bullying perpetration, and "negative affect" was operationalized as anxiety and depression. Analyses were carried out based on a group of 2,139 Macanese schoolchildren. Using a structural equation modeling technique, the results revealed that exposure to family dysfunction and bullying victimization was associated with adolescents' negative affect, such as anxiety and depression. Contrary to our expectations, the indirect effect of victimization on bullying through negative affect was negative, though the mediation effect was relatively small and only significant in boys. In addition, gender analyses of invariance showed that male adolescents who experienced more family conflict and parental control were less likely to engage in bullying. This study could lead to further anti-bullying interventions and practical efforts designed to improve positive parenting and adolescents' interpersonal skills.

Ultrasound-Triggered Liposomes Encapsulating Quantum Dots as Safe Fluorescent Markers for Colorectal Cancer.

Quantum dots (QDs) are a promising tool to detect and monitor tumors. However, their small size allows them to accumulate in large quantities inside the healthy cells (in addition to the tumor cells), which increases their toxicity. In this study, we synthesized stealth liposomes encapsulating hydrophilic graphene quantum dots and triggered their release with ultrasound with the goal of developing a safer and well-controlled modality to deliver fluorescent markers to tumors. Our results confirmed the successful encapsulation of the QDs inside the core of the liposomes and showed no effect on the size or stability of the prepared liposomes. Our results also showed that low-frequency ultrasound is an effective method to release QDs encapsulated inside the liposomes in a spatially and temporally controlled manner to ensure the effective delivery of QDs to tumors while reducing their systemic toxicity.

Ultrasound-Mediated Cancer Therapeutics Delivery using Micelles and Liposomes: A Review.

BACKGROUND: Existing cancer treatment methods have many undesirable side effects that greatly reduce the quality of life of cancer patients. OBJECTIVE: This review will focus on the use of ultrasound-responsive liposomes and polymeric micelles in cancer therapy. METHODS: This review presents a survey of the literature regarding ultrasound-triggered micelles and liposomes using articles recently published in various journals, as well as some new patents in this field. RESULTS: Nanoparticles have proven promising as cancer theranostic tools. Nanoparticles are selective in nature, have reduced toxicity, and controllable drug release patterns making them ideal carriers for anticancer drugs. Numerous nanocarriers have been designed to combat malignancies, including liposomes, micelles, dendrimers, solid nanoparticles, quantum dots, gold nanoparticles, and, more recently, metal-organic frameworks. The temporal and spatial release of therapeutic agents from these nanostructures can be controlled using internal and external triggers, including pH, enzymes, redox, temperature, magnetic and electromagnetic waves, and ultrasound. Ultrasound is an attractive modality because it is non-invasive, can be focused on the diseased site, and has a synergistic effect with anticancer drugs. CONCLUSION: The functionalization of micellar and liposomal surfaces with targeting moieties and the use of ultrasound as a triggering mechanism can help improve the selectivity and enable the spatiotemporal control of drug release from nanocarriers.

Modeling of Anti-Cancer Drug Release Kinetics From Liposomes and Micelles: A Review.

Nanocarriers, such as liposomes and micelles, were developed to enhance the delivery of therapeutic drugs to malignant tissues. Internal or external stimuli can be applied to achieve spatiotemporal controlled release from these carriers. This will result in enhancing their therapeutic efficacy while reducing toxicity. Mathematical modeling is used to simulate drug release from nanocarriers; this will facilitate and optimize the development and design of desirable nanocarriers in a systematic manner, rather than a trial-and-error approach. This review summarizes nine mathematical models often used to simulate drug release from nanocarriers and reviews studies which employed these models to simulate drug release from conventional as well as temperature-, pH-, and ultrasound-triggered micelles and liposomes.

Transferrin-modified liposomes triggered with ultrasound to treat HeLa cells.

Targeted liposomes are designed to target specific receptors overexpressed on the surfaces of cancer cells. This technique ensures site-specific drug delivery to reduce undesirable side effects while enhancing the efficiency of the encapsulated therapeutics. Upon reaching the tumor site, these liposomes can be triggered to release their content in a controlled manner using ultrasound (US). In this study, drug release from pegylated calcein-loaded liposomes modified with transferrin (Tf) and triggered with US was evaluated. Low-frequency ultrasound at 20-kHz using three different power densities (6.2 mW/cm2, 9 mW/cm2 and 10 mW/cm2) was found to increase calcein release. In addition, transferrin-conjugated pegylated liposomes (Tf-PEG liposomes) were found to be more sonosensitive compared to the non-targeted (control) liposomes. Calcein uptake by HeLa cells was found to be significantly higher with the Tf-PEG liposomes compared to the non-targeted control liposomes. This uptake was further enhanced following the exposure to low-frequency ultrasound (at 35 kHz). These findings show that targeted liposomes triggered with US have promising potential as a safe and effective drug delivery platform.

Child abuse: A social evil in Indian perspective.

Child abuse is a social evil which has existed in our society since a long time. The awareness regarding the same has been minimal in developing countries. Many a times, punitive measures taken by parents to discipline their children turn out to be painful scars in their childhood resulting in stunting of their mental and social growth. Doctors and other health care workers have a very important role in identifying and reporting such issues. Law has also evolved over the recent past in safeguarding the future of our children. However, awareness regarding this issue has remained to be the same as before. During the current era of COVID, parents and children have been restricted to their homes. Livelihood of many families have been at risk. These issues have burdened the caretakers at home and absence of teachers who were otherwise their guardian angels have impacted the minds of these children adversely. Hence in this article we intend to provide good clarity about this social evil, and the rights of our children. We also wish to stress upon the duties of parents, doctors, teachers in molding these tender minds so as to get the best out of them.

Ultrasound-Responsive Nanocarriers in Cancer Treatment: A Review.

The safe and effective delivery of anticancer agents to diseased tissues is one of the significant challenges in cancer therapy. Conventional anticancer agents are generally cytotoxins with poor pharmacokinetics and bioavailability. Nanocarriers are nanosized particles designed for the selectivity of anticancer drugs and gene transport to tumors. They are small enough to extravasate into solid tumors, where they slowly release their therapeutic load by passive leakage or biodegradation. Using smart nanocarriers, the rate of release of the entrapped therapeutic(s) can be increased, and greater exposure of the tumor cells to the therapeutics can be achieved when the nanocarriers are exposed to certain internally (enzymes, pH, and temperature) or externally (light, magnetic field, and ultrasound) applied stimuli that trigger the release of their load in a safe and controlled manner, spatially and temporally. This review gives a comprehensive overview of recent research findings on the different types of stimuli-responsive nanocarriers and their application in cancer treatment with a particular focus on ultrasound.

Ultrasound-triggered herceptin liposomes for breast cancer therapy.

The functionalization of liposomes with monoclonal antibodies is a potential strategy to increase the specificity of liposomes and reduce the side-effects associated with chemotherapeutic agents. The active targeting of the Human Epidermal growth factor Receptor 2 (HER2), which is overexpressed in HER2 positive breast cancer cells, can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized calcein and Doxorubicin-loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab (TRA). Both liposomes were characterized for their size, phospholipid content and antibody conjugation. Exposing the liposomes to low-frequency ultrasound (LFUS) triggered drug release which increased with the increase in power density. Trastuzumab conjugation resulted in enhancing the sensitivity of the liposomes to LFUS. Compared to the control liposomes, TRA-liposomes showed higher cellular toxicity and higher drug uptake by the HER2 + cell line (SKBR3) which was further improved following sonication with LFUS. Combining immunoliposomes with LFUS is a promising technique in the field of targeted drug delivery that can enhance efficiency and reduce the cytotoxicity of antineoplastic drugs.