Non-Invasive Intranasal Delivery of pApoE2: Effect of Multiple Dosing on the ApoE2 Expression in Mice Brain.

Chitosan-based polymeric micelles are promising non-viral nanocarriers for safe and targeted gene delivery. Multi-functionalized chitosan polymeric micelles were prepared by grafting fatty acid, cell-penetrating peptide, and mannose on the chitosan backbone. The polymeric micelles were subjected to surface morphology and surface topography using scanning electron microscopy and atomic force microscopy, respectively. The hemotoxic profile of the prepared polymeric micelles was established against erythrocytes and was found to be <5% hemotoxic up to the concentration of 600 µg/mL. In vitro ApoE2 expression in primary astrocytes and neurons was analyzed. Multi-functionalized polymeric micelles produced greater (p < 0.05) transfection in astrocytes and neurons in comparison to mono-functionalized micelles. Intranasal administration of polymeric micelles/pApoE2 polyplex led to significantly higher (p < 0.05) in vivo pApoE2 expression than chitosan and unfunctionalized polymeric micelles-treated mice groups. The outcomes of this study predict that the developed multi-functionalized polymeric micelles could be an effective and safe gene delivery platform to the brain through the intranasal route.

Functional Reconstruction of Through and Through Cheek Defect with Free Composite Bi-pedalled Anterolateral Thigh Flap.

Extensive composite defects involving the lip and cheek present difficult reconstructive challenges in view of functional recovery like oral competence, articulation, speech and mastication. This study presents our results of reconstructing through and through cheek defect with the use of free anterolateral thigh (ALT) flaps. All the patients with carcinoma of buccal mucosa and cheek who underwent through and through cheek resection and reconstructed with free composite pedalled anterolateral thigh flap between March 2019 to March 2020 were included in the study. We have assessed the post-operative functional outcome using University of Washington Quality of Life Questionnaire at the end of 12 months duration. We have excluded lost to follow-up and flap failure patients. Fifty patients were matched our inclusion criteria. Mean age was 43 years. Male to female ratio was 4.6:1. Stage 3 disease was in 8 patients and stage 4 disease was in 42 patients. Average size of the flap required was 15 × 7.5 cm, maximum was 24 × 11 cm. Oral competence was good in 74% patients. 80% patients were able to take semisolid diet, 8% were on liquid diet and 12% were dependent on RT feed. Average physical function (70.47 ± 19.09), social-emotional sub-score (81.72 ± 16.63) and composite scores (76.09 ± 17.86) were good and within acceptable range. Chewing (53 ± 29.29) and swallowing (64 ± 21.57) scored poorly among 12 domains. For extensive through and through cheek defects bipedelled ALT provides good functional outcome. In view of advance disease status extensive resection would be responsible for bone and mucosal loss affecting chewing and swallowing. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03416-3.

Integration of cyclodextrins and associated toxicities: A roadmap for high quality biomedical applications.

Cyclodextrins are extensively employed in drug delivery systems like inclusion complexes, metal-organic frameworks, functionalized or PEGylated conjugates, and other nanocarrier systems such as nanosponges or hydrogel nanoparticles for targeted effect or prolonged release action. Applications of CDs range from drug-loaded nanocarrier systems useful for disease conditions (such as cancer, diabetes, and bacterial infections, etc.) to supramolecular chemistry, diagnostics, imaging, biosensors, and medical devices. However, there is a limited data and information on the adverse effects caused by cyclodextrins and their toxicities in the medical field. Various in-vitro and ex-vivo toxic effects such as cytotoxicity, ototoxicity, etc. as well as the adverse and toxic effects depend on the role of administration of cyclodextrins. This review article focuses on the advancement of characteristics, properties and chemistry of cyclodextrins and addresses the new challenges faced in cyclodextrin-based delivery systems and the various toxicities induced by them.

Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route.

Multifunctional fatty acid grafted polymeric micelles are an effective and promising approach for drug and gene delivery to the brain. An alternative approach to bypass the blood-brain barrier is administration through intranasal route. Multifunctional fatty acid grafted polymeric micelles were prepared and characterized for pVGF delivery to the brain. In vitro pVGF expression was analyzed in bEnd.3 cells, primary astrocytes, and neurons. Comparative in-vivo pVGF expression was analyzed to evaluate the effective route of administration between intranasal and intravenous. Biocompatible, multifunctional polymeric micelles were prepared, having an average size of 200 nm, and cationic zeta potential. Modified polymers were found to be hemo- and cyto-compatible. When transfected with the different modified chitosan formulations, significantly (p < 0.05) higher VGF expression was observed in primary astrocytes and neurons using the mannose, Tat peptide, and oleic acid grafted chitosan polymer. Compared to intravenous administration, intranasal administration of pVGF in polyplex formulation led to significantly (p < 0.05) higher pVGF expression. Developed multifunctional polymeric micelles were an effective pVGF delivery platform to the brain. Mannose and Tat ligand tagging improved the pVGF delivery to the brain.

Nanotech-based Food: An Initiative for Alternative Pharmaceuticals.

Nanotechnology opens many avenues in the food sector and offers applications associated with food production, processing, cultivation, and packaging. Nanofood employs nanotechniques like nano-encapsulation to conjugate various phytochemicals, antioxidants, probiotics, minerals, vitamins, etc., into nanovehicles. Food fortification strategies are implemented to incorporate nano-processed substances. Nanofood is mostly used for improving health and as a supplementation in various diseases ranging from liver diseases to neurodegenerative disorders. Here, we focus on recent studies that exhibit comparable results for nanofood and conventional medicines, subsiding the limitations of traditional therapies. Nanofood holds the potential for the management of various health problems and can be used as an alternative to medicine in clinical conditions, like cancers and inflammatory bowel disease. With further advances in nanotechnology and expansion in the scope of the current nanofood industry, in addition to proper regulations set in place, nanofood may offer a wide variety of advantages in terms of safety, long-term stability, etc.

Methanolic extract of Cucumis melo attenuates ethylene glycol-induced nephrolithiasis in Wistar rats.

Evaluation of the effects of methanolic extract of Cucumis melo in ethylene glycol-induced nephrolithiasis on Wistar rats. 0.75% solution of ethylene glycol (EG) in payable water was given to produce nephrolithiasis on Wistar rats. The action of oral intake of methanolic extract of Cucumis melo seed in nephrolithiasis is studied and is matched with the action of oral intake of Cystone (standard) on Wistar rats. EG resulted in hyperoxaluria and deposition of calcium oxalate as well as raised urinary excretion of oxalate and calcium. Supplementation with methanolic extract of Cucumis melo seed decreased the increased renal oxalate, indicating a regulatory effect on oxalate formation endogenously. The outcomes stipulate that the seed of Cucumis melo is endowed with antinephrolithiatic action.

Delivery systems for improving iron uptake in anemia.

Anemia poses a threat to a broad population globally as depleted hemoglobin leads to a plethora of conditions, and the most common cause includes iron deficiency. Iron is an essential element important for erythropoiesis, DNA synthesis, protection of the immune system, energy production, and cognitive function and hence should be maintained at appropriate levels. Various proteins are involved in transporting and absorption of iron, activation of heme synthesis, and RBC production that could be possible targets to improve iron delivery. Oral supplementation of iron either from dietary or synthetic sources has been the frontline therapy for treating iron deficiency in anemia. At the same time, intravenous administration is provided in chronic anemia, such as chronic kidney diseases (CKD). This review focuses on the strategies developed to overcome the disadvantages of available iron therapies and increase iron absorption and uptake in the body to restore iron content. Nanotechnology combined with the food fortification processes gained attention as they help develop new delivery systems to improve iron uptake by enterocytes. Furthermore, naturally obtained products such as polysaccharides, peptides, proteins, and new synthetic molecules have been used in fabrication of iron-carrier systems. The establishment of transdermal iron delivery systems such as microneedle arrays or iontophoresis, or the discovery of new molecules also proved to be an effective way for delivering iron in patients non-compliant to oral therapy.

3D Printed Bioconstructs: Regenerative Modulation for Genetic Expression.

Layer-by-layer deposition of cells, tissues and similar molecules provided by additive manufacturing techniques such as 3D bioprinting offers safe, biocompatible, effective and inert methods for the production of biological structures and biomimetic scaffolds. 3D bioprinting assisted through computer programmes and software develops mutli-modal nano- or micro-particulate systems such as biosensors, dosage forms or delivery systems and other biological scaffolds like pharmaceutical implants, prosthetics, etc. This review article focuses on the implementation of 3D bioprinting techniques in the gene expression, in gene editing or therapy and in delivery of genes. The applications of 3D printing are extensive and include gene therapy, modulation and expression in cancers, tissue engineering, osteogenesis, skin and vascular regeneration. Inclusion of nanotechnology with genomic bioprinting parameters such as gene conjugated or gene encapsulated 3D printed nanostructures may offer new avenues in the future for efficient and controlled treatment and help in overcoming the limitations faced in conventional methods. Moreover, expansion of the benefits from such techniques is advantageous in real-time delivery or in-situ production of nucleic acids into the host cells. Aspects of 3D bioprinting in gene delivery.

Gut microbiome a promising target for management of respiratory diseases.

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

Treatment of insulin resistance in obesity-associated type 2 diabetes mellitus through adiponectin gene therapy.

Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a major healthcare crisis. Development of efficient treatments to treat the underlying chronic inflammation in obesity-associated T2DM, is an unmet medical need. To this end, we have developed a plasmid adiponectin (pADN) based nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is downregulated in obesity. In this study, nanomicelles comprising chitosan conjugated to oleic acid and adipose homing peptide (AHP) were developed to deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112 nm in size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated enzymatic degradation. In vitro, the nanomicellar formulation significantly increased adiponectin production compared to free plasmid as well as standard transfecting agent FuGENE®HD. Single dose subcutaneous administration of pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin sensitivity for up to 6 weeks, which matched the glucose disposal ability of healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was comparable to healthy rats for up to 3 weeks post treatment. Overall, the results indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment approach for obesity-associated T2DM.