α-Amylase inhibitory, antioxidant and emulsification potential of glycoproteinaceous bioactive molecule from Lactobacillus delbrueckii.

The bioactive components of microbial origin have been extensively applied to restrict the enormous enzyme-catalyzed processes. Hence, the present study was executed to explore the α -amylase inhibition (AAI) potential of glycoprotein isolated from Lactobacillus delbrueckii (LGp) to regulate in vitro starch hydrolysis. As a non-competitive inhibitor, the protein exhibited AAI (85%) with, IC50 135 ± 0.55 µg/mL. It was stable over a broad range of pH (3-11) and temperature (25-75 °C). Furthermore, LGp was significantly effective against amylase and starch from different sources. In addition, it also exhibited antioxidant and emulsifying potential. The UV, FT-IR and fluorescence analysis affirm the alterations in amylase molecular conformation after interaction with the LGp inhibitor. These results provide a substantial basis for the future use of LGp for controlled starch hydrolysis in vitro and as an antioxidant and emulsifying agent in the food industry.

Multifunctionalized Cationic Chitosan Polymeric Micelles Polyplexed with pVGF for Noninvasive Delivery to the Mouse Brain through the Intranasal Route for Developing Therapeutics for Alzheimer's Disease.

Multifunctionalized Chitosan-based polymeric micelles were used to deliver pVGF to the brain. VGF (non-acronymic) plays significant roles in neurogenesis and learning as well as synaptic and cognitive functions. Therefore, VGF gene therapy could be a better approach in developing effective therapeutics against Alzheimer's disease. Multifunctionalized chitosan polymeric micelles were developed by grafting oleic acid (OA) on the chitosan (CS) skeleton followed by penetratin (PEN) and mannose (MAN) conjugation. The OA-g-CS-PEN-MAN graft polymer formed cationic nanomicelles in an aqueous medium and polyplexed with pVGF. The polymeric micelles were nontoxic and cationic in charge and had an average hydrodynamic diameter of 199.8 ± 15.73 nm. Qualitative in vitro transfection efficiency of OA-g-CS-PEN-MAN/pGFP polyplex was investigated in bEnd.3, primary neurons, and astrocyte cells. In vivo transfection efficiency of OA-g-CS-PEN-MAN/pVGF polyplexes was analyzed in C57BL6/J mice after intranasal administration for 7 days. The VGF expression levels in primary astrocytes and neurons after OA-g-CS-PEN-MAN/pVGF treatment were 2.4 ± 0.24 and 1.49 ± 0.02 pg/µg of protein, respectively. The VGF expression in the OA-g-CS-PEN-MAN/pVGF polyplex-treated animal group was 64.9 ± 12.7 pg/mg of protein, significantly higher (p < 0.01) than that of the unmodified polymeric micelles. The in vivo transfection outcomes revealed that the developed multifunctionalized OA-g-CS-PEN-MAN polymeric micelles could effectively deliver pVGF to the brain, transfect brain cells, and express VGF in the brain after noninvasive intranasal administration.

Neurogenic Hypertension, the Blood-Brain Barrier, and the Potential Role of Targeted Nanotherapeutics.

Hypertension is a major health concern globally. Elevated blood pressure, initiated and maintained by the brain, is defined as neurogenic hypertension (NH), which accounts for nearly half of all hypertension cases. A significant increase in angiotensin II-mediated sympathetic nervous system activity within the brain is known to be the key driving force behind NH. Blood pressure control in NH has been demonstrated through intracerebrovascular injection of agents that reduce the sympathetic influence on cardiac functions. However, traditional antihypertensive agents lack effective brain permeation, making NH management extremely challenging. Therefore, developing strategies that allow brain-targeted delivery of antihypertensives at the therapeutic level is crucial. Targeting nanotherapeutics have become popular in delivering therapeutics to hard-to-reach regions of the body, including the brain. Despite the frequent use of nanotherapeutics in other pathological conditions such as cancer, their use in hypertension has received very little attention. This review discusses the underlying pathophysiology and current management strategies for NH, as well as the potential role of targeted therapeutics in improving current treatment strategies.

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.

Experimental Models of In Vitro Blood-Brain Barrier for CNS Drug Delivery: An Evolutionary Perspective.

Central nervous system (CNS) disorders represent one of the leading causes of global health burden. Nonetheless, new therapies approved against these disorders are among the lowest compared to their counterparts. The absence of reliable and efficient in vitro blood-brain barrier (BBB) models resembling in vivo barrier properties stands out as a significant roadblock in developing successful therapy for CNS disorders. Therefore, advancement in the creation of robust and sensitive in vitro BBB models for drug screening might allow us to expedite neurological drug development. This review discusses the major in vitro BBB models developed as of now for exploring the barrier properties of the cerebral vasculature. Our main focus is describing existing in vitro models, including the 2D transwell models covering both single-layer and co-culture models, 3D organoid models, and microfluidic models with their construction, permeability measurement, applications, and limitations. Although microfluidic models are better at recapitulating the in vivo properties of BBB than other models, significant gaps still exist for their use in predicting the performance of neurotherapeutics. However, this comprehensive account of in vitro BBB models can be useful for researchers to create improved models in the future.

Agronomic biofortification of forage crops with zinc and copper for enhancing nutritive potential: a systematic review.

Many developing countries are facing a silent increase in deficiency of micronutrients in forage crops that results in decreased levels of essential nutrients in animals. Micronutrients are essential not only for basic metabolic processes of forage crops but also for sustaining animal health. Forage productivity and quality are severely affected by soil micronutrients deficiencies, especially zinc and copper. This review summarizes the literature highlighting the significance of different methodologies used to increase the biomass and quality of forage so as to enhance the micronutrient content of the forage crops through biofortification. Biofortification is a promising and sustainable agriculture-based strategy to reduce micronutrient deficiency in crops. The experiments and trials conducted at different locations of the world showed that copper and zinc concentrations in animal fodders can be enhanced through the process of foliar application. Additionally, agronomic biofortification showed more promising results, and thus is an outstanding, fast, and cost-effective technique for the immediate enrichment of forage in order to overcome malnutrition in animals. © 2022 Society of Chemical Industry.

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics.

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative disorders include Alzheimer's and Parkinson's disease. Although there are several medicines currently approved for managing neurodegenerative disorders, a large majority of them only help with associated symptoms. This lack of pathogenesis-targeting therapies is primarily due to the restrictive effects of the blood-brain barrier (BBB), which keeps close to 99% of all "foreign substances" out of the brain. Since their discovery, nanoparticles have been successfully used for targeted delivery into many organs, including the brain. This review briefly describes the pathophysiology of Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis, and their current management approaches. We then highlight the major challenges of brain-drug delivery, followed by the role of nanotherapeutics for the diagnosis and treatment of various neurological disorders.

A Review of Brain-Targeted Nonviral Gene-Based Therapies for the Treatment of Alzheimer's Disease.

Diseases of the central nervous system (CNS) are difficult to treat owing to the complexity of the brain and the presence of a natural blood-brain-barrier (BBB). Alzheimer's disease (AD) is one of the major progressive and currently incurable neurodegenerative disorders of the CNS, which accounts for 60-80% of cases of dementia. The pathophysiology of AD involves the accumulation of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) in the brain. Additionally, synaptic loss and imbalance of neuronal signaling molecules are characterized as important markers of AD. Existing treatments of AD help in the management of its symptoms and aim toward the maintenance of cognitive functions, behavior, and attenuation of gradual memory loss. Over the past decade, nonviral gene therapy has attracted increasing interest due to its various advantages over its viral counterparts. Moreover, advancements in nonviral gene technology have led to their increasing contributions in clinical trials. However, brain-targeted nonviral gene delivery vectors come across various extracellular and intracellular barriers, limiting their ability to transfer the therapeutic gene into the target cells. Chief barriers to nonviral gene therapy have been discussed briefly in this review. We have also highlighted the rapid advancement of several nonviral gene therapies for AD, which are broadly categorized into physical and chemical methods. These methods aim to modulate Aß, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), apolipoprotein E, or neurotrophic factors' expression in the CNS. Overall, this review discusses challenges and recent advancements of nonviral gene therapy for AD.

Design and Validation of Liposomal ApoE2 Gene Delivery System to Evade Blood-Brain Barrier for Effective Treatment of Alzheimer's Disease.

Targeting gene-based therapeutics to the brain is a strategy actively sought to treat Alzheimer's disease (AD). Recent findings discovered the role of apolipoprotein E (ApoE) isoforms in the clearance of toxic amyloid beta proteins from the brain. ApoE2 isoform is beneficial for preventing AD development, whereas ApoE4 is a major contributing factor to the disease. In this paper, we demonstrated efficient brain-targeted delivery of ApoE2 encoding plasmid DNA (pApoE2) using glucose transporter-1 (glut-1) targeted liposomes. Liposomes were surface-functionalized with a glut-1 targeting ligand mannose (MAN) and a cell-penetrating peptide (CPP) to enhance brain-targeting and cellular internalization, respectively. Among various CPPs, rabies virus glycoprotein peptide (RVG) or penetratin (Pen) was selected as a cell-penetration enhancer. Dual (RVGMAN and PenMAN)-functionalized liposomes were cytocompatible at 100 nM phospholipid concentration and demonstrated significantly higher expression of ApoE2 in bEnd.3 cells, primary neurons, and astrocytes compared to monofunctionalized and unmodified (plain) liposomes. Dual-modified liposomes also showed ∼2 times higher protein expression than other formulation controls in neurons cultured below the in vitro BBB model. These results translated well to in vivo efficacy study with significantly higher transfection of pApoE2 in the C57BL/6 mice brain following single tail vein administration of RVGMAN and PenMAN functionalized liposomes without any noticeable signs of toxicity. These results illustrate the potential of surface-modified liposomes for safe and brain-targeted delivery of the pApoE2 gene for effective AD therapy.

A novel insight into transcriptional and epigenetic regulation underlying sex expression and flower development in melon (Cucumis melo L.).

Melon (Cucumis melo L.) is an important cucurbit and has been considered as a model plant for studying sex determination. The four most common sexual morphotypes in melon are monoecious (A-G-M), gynoecious (--ggM-), andromonoecious (A-G-mm), and hermaphrodite (--ggmm). Sex expression in melons is complex, as the genes and associated networks that govern the sex expression are not fully explored. Recently, RNA-seq transcriptomic profiling, ChIP-qPCR analysis integrated with gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathways predicted the differentially expressed genes including sex-specific ACS and ACO genes, in regulating the sex-expression, phytohormonal cross-talk, signal transduction, and secondary metabolism in melons. Integration of transcriptional control through genetic interaction in between the ACS7, ACS11, and WIP1 in epistatic or hypostatic manner, along with the recruitment of H3K9ac and H3K27me3, epigenetically, overall determine sex expression. Alignment of protein sequences for establishing phylogenetic evolution, motif comparison, and protein-protein interaction supported the structural conservation while presence of the conserved hydrophilic and charged residues across the diverged evolutionary group predicted the functional conservation of the ACS protein. Presence of the putative cis-binding elements or DNA motifs, and its further comparison with DAP-seq-based cistrome and epicistrome of Arabidopsis, unraveled strong ancestry of melons with Arabidopsis. Motif comparison analysis also characterized putative genes and transcription factors involved in ethylene biosynthesis, signal transduction, and hormonal cross-talk related to sex expression. Overall, we have comprehensively reviewed research findings for a deeper insight into transcriptional and epigenetic regulation of sex expression and flower development in melons.

Improved insulin sensitivity in obese-diabetic mice via chitosan Nanomicelles mediated silencing of pro-inflammatory Adipocytokines.

Obesity induced chronic low-level inflammation is strongly associated with the development of insulin resistance and progression of type-2 diabetes. Systemic treatment with anti-inflammatory therapeutics requires high doses and is associated with serious adverse effects owing to generalized suppression of the immune system. Here we study localized knockdown of pro-inflammatory adipocytokines in adipose tissue macrophages (ATMs) and adipocytes using RNA interference for the treatment of insulin resistance. Chitosan nanomicelles conjugated to ATM and adipocyte targeting ligands were used to transfect short hairpin RNA (shRNA) against tumor necrosis factor-α (TNFα) and monocyte chemoattractant protein-1 (MCP-1). Subcutaneous administration of nanomicellar/pDNA polyplexes in obese-diabetic mice resulted in decreased concentration of pro-inflammatory cytokines TNFα, MCP-1, IL-6, and IL-1ß along with increased concentration of insulin-sensitizing adipokine adiponectin. Downregulation of inflammatory cytokines resulted in improved insulin sensitivity and glucose tolerance for up to six-weeks following single dose, compared to untreated obese-diabetic mice.

Bhendi Yellow Vein Mosaic Virus and Bhendi Yellow Vein Mosaic Betasatellite Cause Enation Leaf Curl Disease and Alter Host Phytochemical Contents in Okra.

Whitefly (Bemisia tabaci)-transmitted begomoviruses cause severe diseases in numerous economically important dicotyledonous plants. Okra enation leaf curl disease (OELCuD) has emerged as a serious threat to okra (Abelmoschus esculentus L. Moench) cultivation in the Indian subcontinent. This study reports the association of a monopartite begomovirus (bhendi yellow vein mosaic virus; BYVMV) and betasatellite (bhendi yellow vein mosaic betasatellite; BYVB) with OELCuD in the Mau region of Uttar Pradesh, India. The BYVMV alone inoculated Nicotiana benthamiana and A. esculentus cv. Pusa Sawani plants developed mild symptoms. Co-inoculation of BYVMV and BYVB resulted in a reduced incubation period, an increased symptom severity, and an enhanced BYVMV accumulation by Southern hybridization and quantitative real-time PCR. This is the first study that satisfies Koch's postulates for OELCuD in its natural host. Activities of various antioxidative enzymes were significantly increased in the virus-inoculated okra plants. Differential responses in various biochemical components (such as photosynthetic pigments, phenol, proline, and sugar) in diseased okra plants were observed. This change in phytochemical responses is significant in understanding its impact on virus pathogenesis and disease development.

Dual-Modified Liposome for Targeted and Enhanced Gene Delivery into Mice Brain.

The development of neuropharmaceutical gene delivery systems requires strategies to obtain efficient and effective brain targeting as well as blood-brain barrier (BBB) permeability. A brain-targeted gene delivery system based on a transferrin (Tf) and cell-penetrating peptide (CPP) dual-functionalized liposome, CPP-Tf-liposome, was designed and investigated for crossing BBB and permeating into the brain. We selected three sequences of CPPs [melittin, Kaposi fibroblast growth factor (kFGF), and penetration accelerating sequence-R8] and compared their ability to internalize into the cells and, subsequently, improve the transfection efficiency. Study of intracellular uptake indicated that liposomal penetration into bEnd.3 cells, primary astrocytes, and primary neurons occurred through multiple endocytosis pathways and surface modification with Tf and CPP enhanced the transfection efficiency of the nanoparticles. A coculture in vitro BBB model reproducing the in vivo anatomophysiological complexity of the biologic barrier was developed to characterize the penetrating properties of these designed liposomes. The dual-functionalized liposomes effectively crossed the in vitro barrier model followed by transfecting primary neurons. Liposome tissue distribution in vivo indicated superior ability of kFGF-Tf-liposomes to overcome BBB and reach brain of the mice after single intravenous administration. These findings demonstrate the feasibility of using strategically designed liposomes by combining Tf receptor targeting with enhanced cell penetration as a potential brain gene delivery vector. SIGNIFICANCE STATEMENT: Rational synthesis of efficient brain-targeted gene carrier included modification of liposomes with a target-specific ligand, transferrin, and with cell-penetrating peptide to enhance cellular internalization. Our study used an in vitro triple coculture blood-brain barrier (BBB) model as a tool to characterize the permeability across BBB and functionality of designed liposomes prior to in vivo biodistribution studies. Our study demonstrated that rational design and characterization of BBB permeability are efficient strategies for development of brain-targeted gene carriers.

Nerve Growth Factor Gene Delivery across the Blood-Brain Barrier to Reduce Beta Amyloid Accumulation in AD Mice.

The therapeutic potential of the nerve growth factor (NGF) gene using brain-targeted liposomal nanoparticles was investigated for the treatment of Alzheimer's disease (AD). We designed brain-targeted gene delivery systems with prolonged systemic circulation and enhanced cellular penetration by conjugating the transferrin (Tf) ligand and the penetratin (Pen) peptide to liposomes via a 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) phospholipid. In vitro characterization studies showed that the nanoparticles had homogeneous particle size and positive zeta potential and were able to protect the plasmid DNA against enzymatic degradation. In vivo brain targeting efficiency of designed liposomes was mimicked using an in vitro triple coculture blood-brain barrier (BBB) model. Liposomal nanoparticles dual-modified with Tf and Pen encasing plasmid NGF efficiently crossed the in vitro BBB model and, subsequently, transfected the primary neuronal cells. Increasing NGF expression in primary neuronal cells following treatment with liposomes increased the levels of the presynaptic marker synaptophysin in vitro. A dose-response study in vivo was performed in order to select the appropriate dose of plasmid NGF to induce significant NGF expression and, consequently, a therapeutic effect. Administration of PenTf-liposomes containing pNGF to amyloid precursor protein (APP)/PS1 mice (aged 3 months) for 4 weeks (one injection per week) significantly decreased (p < 0.05) the levels of toxic soluble and insoluble Aß peptides as compared to those levels in untreated APP/PS1 mice. Additionally, the treatment stimulated cell proliferation and increased the levels of synaptic markers, synaptophysin and PSD-95. These data suggest the therapeutic potential of PenTf-liposome-mediated NGF gene therapy, and this system can be considered a candidate for the treatment of AD.

In Vitro and in Vivo Optimization of Phase Sensitive Smart Polymer for Controlled Delivery of Rivastigmine for Treatment of Alzheimer's Disease.

PURPOSE: Alzheimer's disease is a neurodegenerative disorder, and most common form of dementia afflicting over 35 million people worldwide. Rivastigmine is a widely used therapeutic for ameliorating clinical manifestations of Alzheimer's disease. However, current treatments require frequent dosing either orally or via transdermal patch that lead to compliance issues and administration errors risking serious adverse effects. Our objective was to develop a smart polymer based delivery system for controlled release of rivastigmine over an extended period following a single subcutaneous injection. METHODS: Rivastigmine release was optimized by tailoring critical factors including polymer concentration, polymer composition, drug concentration, solvent composition, and drug hydrophobicity (rivastigmine tartrate vs base). Optimized in vitro formulation was evaluated in vivo for safety and efficacy. RESULTS: Formulation prepared using PLGA (50:50) at 5% w/v in 95:5 benzyl benzoate: benzoic acid demonstrated desirable controlled drug release characteristics in vitro. The formulation demonstrated sustained release of rivastigmine tartrate for 7 days in vivo with promising biocompatibility and acetylcholinesterase inhibition efficacy for 14 days. CONCLUSION: The results exemplify an easily injectable controlled release formulation of rivastigmine prepared using phase-sensitive smart polymer. The optimized formulation significantly increases the dosing interval, and can potentially improve patient compliance as well as quality of life of patients living with Alzheimer's disease.

In vitro and in vivo characterization of CPP and transferrin modified liposomes encapsulating pDNA.

The limitations imposed on brain therapy by the blood-brain barrier (BBB) have warranted the development of carriers that can overcome and deliver therapeutic agents into the brain. We strategically designed liposomal nanoparticles encasing plasmid DNA for efficient transfection and translocation across the in vitro BBB model as well as in vivo brain-targeted delivery. Liposomes were surface modified with two ligands, cell-penetrating peptide (PFVYLI or R9F2) for enhanced internalization into cells and transferrin (Tf) ligand for targeting transferrin-receptor expressed on brain capillary endothelial cells. Dual-modified liposomes encapsulating pDNA demonstrated significantly (P < 0.05) higher in vitro transfection efficiency compared to single-modified nanoparticles. R9F2Tf-liposomes showed superior ability to cross in vitro BBB and, subsequently, transfect primary neurons. Additionally, these nanoparticles crossed in vivo BBB and reached brain parenchyma of mice (6.6%) without causing tissue damage. Transferrin receptor-targeting with enhanced cell penetration is a relevant strategy for efficient brain-targeted delivery of genes.

Biodistribution of TAT or QLPVM coupled to receptor targeted liposomes for delivery of anticancer therapeutics to brain in vitro and in vivo.

Combination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used two different CPPs (based on physicochemical properties) and investigated the influence of insertion of CPP to Tf-liposomes on biocompatibility, cellular uptake, and transport across the BBB both in vitro and in vivo. The biodistribution profile of Tf-CPP liposomes showed more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively as compared to free drugs with no signs of toxicity.

ApoE-2 Brain-Targeted Gene Therapy Through Transferrin and Penetratin Tagged Liposomal Nanoparticles.

PURPOSE: Apolipoprotein E2 (ApoE2) gene therapy is a potential disease-modifying therapy for Alzheimer's disease (AD). We investigated the potential of plasmid encoding ApoE2 loaded brain-targeted functionalized-liposomes for treatment of AD. This was achieved via systemic administration of liposomes entrapping therapeutic gene targeting the brain of mice. METHODS: Targeting and transfection efficiency of designed liposomes were determined in bEnd.3, primary glial and primary neuronal cells. The ability of liposomal formulations to translocate across in vitro blood-brain barrier (BBB) and, thereafter, transfect primary neuronal cells was investigated using in vitro triple co-culture BBB model. We quantified ApoE expression in the brain of mice after single intravenous injection of brain-targeted liposomes loaded with plasmid ApoE2. RESULTS: Dual surface modification enhanced the in vitro transfection efficiency of designed liposomes. Successful delivery of therapeutic gene overcoming BBB by Transferrin-Penetratin- modified liposomes was demonstrated both in vitro and in vivo. Significant (p < 0.05) increase in ApoE levels in the brain of mice was observed after intravenous administration of Tf-Pen-liposomes encasing plasmid ApoE2. CONCLUSION: The results indicate that dual-ligand based liposomal gene delivery systems had both enhanced brain targeting and gene delivery efficiencies. Transferrin-Penetratin modified liposomes for delivery of plasmid ApoE2 has great potential for AD treatment.

Editorial of Special Issue "Surface-Functionalized Nanoparticles as Drug Carriers".

Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field.

Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications.

The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (∼50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ∼200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.