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Spatiotemporal targeting of anti-glioma drugs remains a pressing issue in glioblastoma (GBM) treatment. We challenge this issue by developing a minimally invasive

The blood-brain barrier (BBB) and tumor heterogeneity have resulted in abysmally poor clinical outcomes in glioblastoma (GBM) with the standard therapeutic regimen. Despite several anti-glioma drug delivery strategies, the lack of adequate chemotherapeutic bioavailability in gliomas has led to a suboptimal therapeutic gain in terms of improvement in survival and increased systemic toxicities. This has paved the way for designing highly specific and non-invasive drug delivery approaches for treating GBM. The intranasal (IN) route is one such delivery strategy that has the potential to reach the brain parenchyma by circumventing the BBB. We recently showed that

The WHO estimates an average of 10 million deaths per year due to the increasing number of infections and the predominance of drug resistance. To improve clinical outcomes and contain the spread of infections, the development of newer diagnostic tools is imperative to reduce the time and cost involved to reach the farthest population. The current study focuses on the development of a point-of-care technology that uses crystal violet entrapped, lectin functionalized chitosan nanoparticles to detect the presence of clinically relevant bacterial infections. Spherical nanoparticles of200 nm in diameter make up the biosensing nanomaterial, showed specific clumping in the presence of bacteria to form visible aggregates as compared to a nonbacterial sample. Visible agglutination confirmed the presence of bacteria in the samples. The devices require just 100 μL of sample and were tested with various bacteria-spiked saline, simulated urine, artificial sputum, and simulated respiratory and wound swabs. The developed device did not require any sample preparation or sophisticated instruments while enabling rapid differentiation between bacterial and nonbacterial infections within 10 min. The

Nanotechnology-based drug delivery platforms have shown great potential in overcoming the limitations of conventional therapy for glioblastoma (GBM). However, permeation across the blood-brain barrier (BBB), physiological complexity of the brain, and glioma targeting strategies cannot entirely meet the challenging requirements of distinctive therapeutic delivery stages. The objective of this research is to fabricate lipid nanoparticles (LNPs) for the co-delivery of paclitaxel (PTX) and miltefosine (HePc) a proapoptotic agent decorated with transferrin (Tf-PTX-LNPs) and investigate its anti-glioma activity both in vitro and in vivo orthotopic NOD/SCID GBM mouse model. The present study demonstrates the anti-glioma effect of the dual drug combination of PTX and proapoptotic HePc lipid-based transferrin receptor (TfR) targeted alternative delivery (direct nose to brain transportation) of the nanoparticulate system (Tf-PTX-LNPs, 364 ± 5 nm, -43 ± 9 mV) to overcome the O

As declared by WHO, antimicrobial resistance (AMR) is a high priority issue with a pressing need to develop impactful technologies to curb it. The rampant and inappropriate use of antibiotics due to the lack of adequate and timely diagnosis is a leading cause behind AMR evolution. Unfortunately, populations with poor economic status and those residing in densely populated areas are the most affected ones, frequently leading to emergence of AMR pathogens. Classical approaches for AMR diagnostics like phenotypic methods, biochemical assays, and molecular techniques are cumbersome and resource-intensive and involve a long turnaround time to yield confirmatory results. In contrast, recent emergence of nanotechnology-assisted approaches helps to overcome challenges in classical approaches and offer simpler, more sensitive, faster, and more affordable solutions for AMR diagnostics. Nanomaterial platforms (metallic, quantum-dot, carbon-based, upconversion, etc.), nanoparticle-based rapid point-of-care platforms, nano-biosensors (optical, mechanical, electrochemical), microfluidic-assisted devices, and importantly, nanotheranostic devices for diagnostics with treatment of AMR infections are examples of rapidly growing nanotechnology approaches used for AMR management. This review comprehensively summarizes the past 10 years of research progress on nanotechnology approaches for AMR diagnostics and for estimating antimicrobial susceptibility against commonly used antibiotics. This review also highlights several bottlenecks in nanotechnology approaches that need to be addressed prior to considering their translation to clinics.

Background: Micronutrient deficiency is a known cause of adverse neurodevelopment and growth. Poor adherence to oral regimes of micronutrient supplements is a known challenge during the implementation of supplementation programs. The present study evaluates the benefits of liposomal encapsulated micronutrient fortified body oils (LMF oil) that can be used for infant body massage in terms of neurodevelopment and prevention of deficiency. Study design: Double-blind randomized clinical trial Methods: 444 healthy infants aged 4-7weeks were randomized to receive either LMF oil (containing iron, vitamin D, folate, and vitamin B12) or placebo oil for gentle body massage till 12months of age. Blood samples were collected at 6 and 12 months for transferrin saturation (TSAT), hemoglobin, and 25-hydroxy vitamin (25-OH-D) levels. Mental and motor development was assessed at 12 months using developmental assessment for Indian Infants (DASII). Results: A total of 391 infants completed the study. There was no significant improvement in the hemoglobin in the intervention group at 12 months of age as compared to the placebo group [-0.50 vs.-0.54 gm%]. There was a marginally significant improvement in 25-OH-D at 12 months in the LMF oil group [+1.46vs.-0.18ng/ml, p=0.049]. In the subgroup of infants with moderate anemia, the intervention prevented the decline in hemoglobin at 12 months of age [adjusted mean change +0.11vs.-0.51gm%, p=0.043]. The mental or motor developmental quotients in the intervention group were not significantly different from those in the placebo group. Conclusion: Use of LMF oil for prevention of nutritional deficiency did not offer significant protection against nutritional anemia but prevented vitamin D deficiency to some extent with improvement in 25-OH-D at 12 months. In the subgroup of infants with moderate anemia, the intervention prevented the decline in hemoglobin at 12 months of age. The intervention did not result in significant improvement in mental or motor development. Further evaluation with increased doses needs to be undertaken.Trial registration: CTRI no: CTRI/2017/11/010710; dated 30/11/2017 [http://ctri.nic.in/Clinicaltrials/advancesearchmain.php ]

The therapeutic gain in loco-regionally advanced unresectable head and neck squamous cell carcinoma (HNSCC) is limited with the traditional use of concurrent chemoradiotherapy (CRT) owing to dose-limiting toxicities of systemic clinical radiosensitizers. Delivery through regional platforms is challenging due to limited drug permeation but allows spatio-temporal control of combinatorial regimens locally to overcome drug resistance. We address these challenges by developing biodegradable gellan- and lipid-based dual nanocarriers-in-ion-triggered porous mucoadhesive hydrogels for enhanced site-specific delivery of clinically relevant radiosensitizers i.e. cisplatin and paclitaxel. Interestingly, the nanoparticle-in-gel prolonged the tumor bioaccumulation of both the chemotherapeutic drugs with reduced systemic absorption, thereby improving in vivo efficacy which was confirmed by PET-CT imaging and safety as compared to systemic commercial formulations approved for HNSCC chemoradiotherapy. The nanoparticles facilitated intracellular radiosensitizer uptake and cell arrest to synergistically enhance radiation-induced DNA nicks and apoptosis. Our findings suggest the clinical potential of the present platform in the loco-regional management of HNSCC requiring curative CRT.

Adequate micronutrient availability is particularly important in women, children and infants. Micronutrient deficiencies are the major cause of maternal and neonatal morbidity. To overcome this, WHO recommends the use of folic acid and iron supplements for reducing anaemia and improving the health of the mother and infants. Oral intake of supplements for nutritional deficiencies are associated with gastric irritation, nausea, constipation and non-patient compliance due to associated taste. In case of absorption deficiency nutrients administered orally pass-through digestive tract unabsorbed. In the present study, we propose transdermal delivery of nutraceuticals to avoid the limitations associated with oral intake. Transdermal delivery has limited use because of the closely packed barrier of the stratum corneum that limits the permeability of molecules across skin. Here, we have used biomimetic nanovesicles impregnated in transdermal patches for delivery of folic acid and iron. Nanovesicles are prepared using an abundant component of cell membrane, phosphatidyl choline and a permeation enhancer. Further these nanovesicles are impregnated onto polyacrylate based transdermal patch. In vitro studies have shown the ability of nanovesicles to fluidise skin lipids and penetrate into deeper skin. In vivo application of transdermal patches gradually increased the systemic concentration of nutraceuticals. Post application of the patch, five-fold increase in plasma folic acid concentration and 1.5-fold increase in plasma iron concertation was achieved in 6 h. Developed nanovesicles were compatible with keratinocytes and fibroblasts as tested in vitro and have the potential to enhance the cellular uptake of molecules. Skin irritation studies on human volunteers have confirmed the safety of nutraceutical loaded nanovesicles. Thus, the developed nutraceutical loaded transdermal patches provide a potential, easy to use platform for micronutrient delivery in infants and mothers.

The increase in drug-resistant strains of Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has led to an increased rate of infection-related mortality. The emergence of drug resistance has rendered many antibiotics ineffective. The poor penetration and retention of antibiotics in mammalian cells lead to recurrent latent infections. Thus, there is an increasing need for biodegradable, non-toxic anti-infectives that are effective in treating MRSA infections. Phytochemicals such as berberine (BBR) and curcumin (CCR) have long been explored for their antibacterial activities, but their efficacy is often limited due to low bioavailability, water solubility, and poor cell penetration. When used in combination these antimicrobials did not show any synergistic effect against MRSA. Here, both of them were co-encapsulated in liposomes (BCL) and evaluated for biocompatibility, synergistic antimicrobial activity, intracellular infections, associated inflammation, and on biofilms formed by MRSA. Co-encapsulation of BBR and CCR in liposomes decreased their MICs by 87% and 96%, respectively, as compared to their free forms with a FICI of 0.13, indicating synergy between them. BCL inhibited the growth of MRSA and prevented biofilm formation better than free drugs. Co-culture studies showed that intracellular infection was reduced to 77% post BCL treatment. It also reduced the production of pro-inflammatory cytokines by macrophages following infection. The liposomes were found to be five times more efficient than clindamycin and can be used as a potential antimicrobial carrier against intracellular infections.

Indian communities have the ancient cultural practice of gentle oil massage for infants which has been shown to play a beneficial role in neuro-motor development. The concept of incorporating nanosized liposomes of micronutrients (i.e., iron, folate, vitamin B12, and vitamin D) in the body oil leverages this practice for transdermal supplementation of essential micro-nutrients. This paper describes the experience of developing an intervention in the form of body oil containing nanosized liposomes of iron and micro-nutrients built on the social context of infant oil massage using a theory of change approach. The process of development of the intervention has been covered into stages such as design, decide and implement. The design phase describes how the idea of nanosized liposomal encapsulated micronutrient fortified (LMF) body oil was conceptualized and how its feasibility was assessed through initial formative work in the community. The decide phase describes steps involved while scaling up technology from laboratory to community level. The implementation phase describes processes while implementing the intervention of LMF oil in a community-based randomized controlled study. Overall, the theory of change approach helps to outline the various intermediate steps and challenges while translating novel technologies for transdermal nutrient fortification to community level. In our experience, adaptation in the technology for large scale up, formative work and pilot testing of innovation at community level were important processes that helped in shaping the innovation. Meticulous mapping of these processes and experiences can be a useful guide for translating similar innovations.

Poor adherence to drug dosing schedule is responsible for ∼50% of hospitalization cases. Most patients fail to adhere to a strict dosing schedule due to invasive drug administration, off-target toxicities, or medical conditions like dementia. The emerging concept of wearable devices (WDs), implantable devices (IDs) and combined wearable and implantable devices (WIDs) for drug delivery has created new opportunities for treating patients with chronic diseases needing repeated and long-term medical attention like diabetes, ocular disorders, cancer, wound healing, cardiovascular diseases, and contraception. WDs, worn on the body surface have created appealing non-invasive, self-administrable drug delivery platforms which receive huge patient compliance. Microneedle-skin patches, wound healing patches, drug-eluting contact lenses, mouth guards, intra-vaginal rings, pharmaceutical jewelry, and drug-loaded self-care textiles are popular WDs explored in drug delivery. In contrast, IDs are surgically placed inside body tissue allowing higher payload and enhanced localized effect for an extended duration. Hormone micropumps, hydrogel/nanofibrous depot, coronary stents, intravitreal devices, and intrauterine devices are some representative examples of IDs. In this review, we have described the past 10 years of research progress on drug-delivering WDs and IDs in the context of treating diseases that demand repeated and long-term medication, especially those affecting soft tissues. We highlighted several technical challenges that need to be addressed before considering the translation of such technologies to clinics.

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca