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Introduction: The incidence of Central Nervous System (CNS) disorders, including Parkinson's disease, Alzheimer's disease, stroke, and malignancies, has risen significantly in recent decades, contributing to millions of deaths annually. Efficacious treatment of these disorders requires medicines targeting the brain. The Blood-brain Barrier (BBB) poses a formidable challenge to effective drug delivery to the brain, hindering progress in CNS therapeutics. This review explores the latest developments in nanoparticulate carriers, highlighting their potential to overcome BBB limitations., Objective: This study aimed to evaluate and summarise the critical factors and pathways in the nanoparticle- based CNS targeted drug delivery., Methods: An extensive literature search was conducted, comprising the initial development of nanoparticle- based CNS-targeted drug delivery approaches to the latest advancements using various online search tools., Results: The properties of nanoparticles, such as type of nanoparticles, size, shape, surface charge, hydrophobicity, and surface functionalisation, along with properties of the BBB during normal and pathological conditions and their impact on the delivery of nanoparticles across the BBB, are identified and discussed here., Conclusion: Important properties and pathways that determine the penetration of nanoparticles across the CNS are reviewed in this article, along with recent advances in the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The complexity of treating neurological diseases has meant that new strategies have had to be developed to deliver drugs to the brain more efficiently and safely. Intranasal drug delivery is characterized by its ease of administration, safety, and rapid delivery directly from the nose to the brain. Several strategies have been developed to improve the delivery of drugs to the brain via nasal administration. These include the use of mucoadhesive and thermoresponsive polymers and their combination into polymer blends, as well as the use of liposomes, niosomes, and nano- and microemulsions. Therefore, this review focuses on technologies for developing pharmaceutical systems aimed at delivery via the nose to the brain, contributing to new treatments for difficult neurological disorders. Some of the most common and difficult-to-treat neurological conditions, the intranasal route of administration, and the anatomy of the nasal cavity have been discussed, as well as factors that may influence the absorption of drugs administered into the nose. The types of intranasal formulations and the devices that can be used to administer these products are also discussed in this review. Strategies for improving the transport of bioactive agents and increasing bioavailability are highlighted. The technologies discussed in this review can facilitate the development of formulations with improved properties, such as drug release and mucoadhesiveness, which have several advantages for patients requiring complex neurological treatments., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Objective: To explore the potential of transnasal drug delivery systems (DDS) as an effective means of bypassing the bloodbrain barrier (BBB) for enhanced central nervous system (CNS) targeting, aiming to improve therapeutic outcomes for CNS disorders while reducing systemic side effects., Methods: A review of current and emerging DDS technologies, including polymer nanoparticles, liposomes, and micelles, was conducted to assess their suitability for precision-targeted delivery to the brain through the transnasal route., Results: The investigated DDS demonstrate promising capabilities for CNS targeting via the nasal pathway, effectively preserving both the nasal mucosa and CNS integrity. These systems enhance drug precision within neural tissues, potentially improving therapeutic outcomes without harming adjacent tissues., Conclusions: Transnasal DDS offer a promising alternative to traditional delivery methods, with significant potential to advance the treatment of cerebrovascular diseases, neurodegenerative disorders, brain tumors, and psychiatric conditions. This approach represents an evolving frontier in neurotherapeutics, with the potential to transform CNS drug delivery practices., Competing Interests: Declarations. Competing Interest: The authors declare that they have no known competing financial interests or personal rela-tionships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intranasal drug delivery route has emerged as a promising non-invasive method of administering drugs directly to the brain, bypassing the blood-brain barrier (BBB) and blood-cerebrospinal fluid barriers (BCSF). BBB and BCSF prevent many therapeutic molecules from entering the brain. Intranasal drug delivery can transport drugs from the nasal mucosa to the brain, to treat a variety of Central nervous system (CNS) diseases. Intranasal drug delivery provides advantages over invasive drug delivery techniques such as intrathecal or intraparenchymal which can cause infection. Many strategies, including nanocarriers liposomes, solid-lipid NPs, nano-emulsion, nanostructured lipid carriers, dendrimers, exosomes, metal NPs, nano micelles, and quantum dots, are effective in nose-to-brain drug transport. However, the biggest obstacles to the nose-to-brain delivery of drugs include mucociliary clearance, poor drug retention, enzymatic degradation, poor permeability, bioavailability, and naso-mucosal toxicity. The current review aims to compile current approaches for drug delivery to the CNS via the nose, focusing on nanotherapeutics and nasal devices. Along with a brief overview of the related pathways or mechanisms, it also covers the advantages of nasal drug delivery as a potential method of drug administration. It also offers several possibilities to improve drug penetration across the nasal barrier. This article overviews various in-vitro, ex-vivo, and in-vivo techniques to assess drug transport from the nasal epithelium into the brain., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes with a new 'complexing excipient' - vitamin B 12 -targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B 12 -internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B 12 receptor-mediated cellular internalization of B 12 -targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2-3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B 12 -targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B 12 -targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite research efforts full potential of siRNA-based therapeutics has not yet been fully realized due to a need for suitable, effective delivery formulations. Here, we examine a potential of a new class of water-soluble chitosans as siRNA platform for pulmonary delivery. The system is based on piperazine-substituted chitosans, a material designed to integrate established, safe application of chitosan for mucosal administration with novel properties: the piperazine-substituted chitosans are freely water-soluble at physiological pH, possess low cytotoxicity (no significant reduction in cell viability up to 0.1 mg/ml), and provide efficient incorporation of siRNA into sub-300 nm colloidal complexes (at relatively low polymer/siRNA ratio of 5:1). In vitro, the complexes achieved silencing of a model gene at a level of 40-80%, when tested in a panel of lung epithelial cells. Considering the formulation 'developability', there were no significant changes in the complexes' size and integrity on aerosolisation by microsprayer (PenCentury™) device. Following intratracheal aerolisation, the complexes deposited throughout the lung, although relatively inhomogeneously, as judged from IVIS imaging of the isolated mouse lung (visualizing DY647-siRNA). In vivo data illustrate absence of adverse effects on repeated administration of complexes and significant tumor reduction in atopical lung cancer model in mice. Altogether, the data illustrates potential of substituted chitosan derivatives to be utilized as a safe system for inhalation delivery of siRNA.

Introduction: Research into oral delivery of biologics has a long and rich history but has not produced technologies used in the clinic. The area has evolved in terms of strategies to promote oral biologics delivery from early chemical absorption enhancers to nanomedicine to devices. Continued activity in this area is justifiable considering the remarkable proliferation of biologics., Areas Covered: The article discusses some physiological barriers to oral delivery of biologics, with a special focus on less characterized barriers such as the basement membrane. Recent progress in oral delivery of biologics via nanomedicine is subsequently covered. Finally, the emerging field of device-mediated gastrointestinal delivery of biotherapeutics is discussed, Expert Opinion: Oral delivery of biologics is considered a 'panacea' in drug delivery. Almost century-old approaches of utilizing chemical absorption enhancers have not produced clinically translated technologies. Nanomedicine for oral biologics delivery has demonstrated potential, but the field is relatively new, and technologies have not progressed to the clinic. Device-mediated oral biologics delivery (e.g. ultrasound or microneedles) is in its infancy. However, this space is likely to intensify owing to advances in electronics and materials, as well as the challenges and history related to clinical translation of alternative approaches.

The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was augmented by addition of chitosan in solution, this was not reflected in the bioelectrical parameters and the metabolic activity of the tissue. Regarding transport across the excised olfactory tissue, none of the nanoparticle systems tested, irrespective of particle size or surface modification, was transported across the epithelium to appear in measurable amounts in the receiver chamber.

This work examines the potential drug delivery barrier of the basement membrane (BM) by assessing the permeability of select macromolecules and nanoparticles. The study further extends to probing the effect of BM on intestinal epithelial cell attachment and monolayer characteristics, including cell morphology. Serum-free cultured Caco-2 cells were grown on BM-containing porous supports, which were obtained by prior culture of airway epithelial cells (Calu-3), shown to assemble and deposit a BM on the growth substrate, followed by decellularisation. Data overall show that the attachment capacity of Caco-2 cells, which is completely lost in serum-free culture, is fully restored when the cells are grown on BM-coated substrates, with cells forming intact monolayers with high electrical resistance and low permeability to macromolecules. Caco-2 cells cultured on BM-coated substrates displayed strikingly different morphological characteristics, suggestive of a higher level of differentiation and closer resemblance to the native intestinal epithelium. BM was found to notably hinder the diffusion of macromolecules and nanoparticles in a size dependent manner. This suggests that the specialised network of extracellular matrix proteins may have a significant impact on transmucosal delivery of certain therapeutics or drug delivery systems., (Copyright © 2014. Published by Elsevier Inc.)

The production of microparticles using a supercritical carbon dioxide based PGSS technique (CriticalMix™) has been exploited to develop blended systems targeted at pulmonary delivery. Hence, PEG based polymers of different molecular weights (1000-6000 Da) were blended in situ with fatty acids (stearic, palmitic or myristic acid) or with commercially available PEG-stearates. The effect of the different thermodynamic properties of the polymers was evaluated by characterising the microparticles produced in terms of their melting temperature by conventional DSC and in the presence of high pressure CO(2) using a high pressure variable volume view cell. The microparticles produced were also assessed by SEM and particle size distribution. It is well known that as the molecular weight of the PEG chains increases, so does the viscosity of the melt and this leads to an increase in the particle size. In the paper we show that blending with myristic acid provides optimal control of particle size when the blend is sprayed from scCO(2) leading to high yields in the optimal aerodynamic size range of 2-5 μm for the deep lung delivery. The highest yield and smallest particles (~5 μm) were produced with a blend of PEG 3000 and myristic acid (1:1) whereas the batches containing palmitic acid and stearic acid showed lower yields and larger particle sizes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In a study directed towards non-invasive delivery of therapeutic biomacromolecules, we examined whether surface modification of sub-200 nm model nanoparticles with the Fc portion of IgG promotes their cell uptake and transport across the airway epithelial cells. The study initially confirms the expression of the relevant receptor, namely neonatal Fc receptor (FcRn), by Calu-3 cell layers simulating the airway epithelium and demonstrates FcRn-mediated cell association, internalization and transcellular transport of molecular IgG. Surface decoration of nanoparticles with the Fc portion of IgG enhanced both cell uptake and translocation of the particulate system across the cell layers, in a manner strongly suggesting FcRn involvement in these processes. The study further demonstrates the potential of Fc-modified nanoparticles to 'shuttle' a model therapeutic antibody fragment across the epithelial cell layers. Fc-modified nanoparticles are transported in the μg/h/cm(2) range, presenting a substantial increase in transport capacity in comparison to molecular IgG (ng/h/cm(2) range), therefore warranting consideration of the FcRn transcytotic pathway for further investigation as a means to achieve transmucosal delivery of nanoparticulate systems that could act as carriers of a range of biotherapeutics., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This review aims to evaluate the evidence for the existence of a direct nose-to-brain delivery route for nanoparticles administered to the nasal cavity and transported via the olfactory epithelium and/or via the trigeminal nerves directly to the CNS. This is relevant in the field of drug delivery as well as for new developments in nanotechnology. Experiments in animal models have shown that nano-sized drug delivery systems can enhance nose-to-brain delivery of drugs compared to equivalent drug solutions formulations. Protection of the drug from degradation and/or efflux back into the nasal cavity may partly be the reason for this effect of nanoparticles. It is uncertain, however, whether drug from the nanoparticles is being released in the nasal cavity or the nanoparticles carrying the drug are transported via the olfactory system or the trigeminal nerves into the CNS where the drug is released. Furthermore, toxicity of nanoparticulate drug delivery systems in the nasal cavity and/or in the CNS has not been extensively studied and needs to be considered carefully.

Small molecular weight drugs, peptides, and nanoparticles have previously been shown to localize in the central nervous system after intraneural administration. A basic understanding of direct nose-to-brain drug delivery, particularly for nanoparticles with different physicochemical characteristics, remains unclear. In this study, fluorescence microscopy and stereology were used to track intranasally administered chitosan-coated polystyrene (C-PS) or polysorbate-coated polystyrene (P80-PS) nanoparticles (100 nm or 200 nm in diameter) in olfactory and respiratory nasal epithelia and olfactory bulbs in mice. Chitosan coating caused particles to adhere to the extracellular mucus which could provide useful modality for paracellular drug transport. Nanoparticle transport was exclusively transcellular. None of the nanoparticle formulations showed preference for uptake into olfactory axons over other nasal epithelial cells. Both 100 nm PS and 100 nm P80-PS were observed in olfactory epithelial cells but were absent from the olfactory bulbs; therefore, it is speculated that an optimal nanoparticle diameter for axonal transport is <100 nm in mice.

Advances in biotechnology have now created a capacity to produce therapeutically active proteins on a commercial scale, opening the potential for their application in an array of disease conditions. The process of translation of the variety of different therapeutic proteins into the medicines used in clinics is now occurring. To assist in this translation, new formulations to deliver proteins could play an important role. These new formulations need to more adequately address the pharmacological and therapeutic requirement for each particular protein/peptide and, in that way, either improve present therapies or extend with new entries the current list of protein based medicines used in clinic.

A novel 2-(dimethylamino)ethyl methacrylate-block-2-(methacryloyloxyethyl phosphorylcholine) (DMAEMA-MPC) diblock copolymer was synthesized and investigated as a new non-viral vector for gene delivery. The attractive perspective of this phosphorylcholine (PC)-based material is its propensity to condense DNA efficiently via the cationic DMAEMA block, as previously demonstrated for the respective homopolymer, with the MPC block acting as a biocompatible steric stabilizer. Two series of DMAEMA-MPC diblock copolymers were synthesized for evaluation, varying independently and systematically either MPC or DMAEMA block length. Markedly different DNA-copolymer complexes were observed depending on the copolymer molecular composition. Certain polymeric structures led to formation of highly condensed, sterically stabilized DNA complexes of 120-140 nm diameter, while some resulted in partly condensed DNA-polymer complexes with 'spaghetti' structures, indicating the importance of a copolymer composition to balance condensing and steric stabilization effect. A low level of non-specific cellular association of the complexes with optimized physicochemical properties was seen, indicating the role of MPC surface layer in the interactions with biological membranes and important property in preventing promiscuous interactions with tissues in the body and potentially allowing for cellular specific delivery of the condensates following the attachment of a targeting ligand.

The optimization of DNA-cationic polymer complexation is crucial for nonviral gene delivery. Although physicochemical characterization of the interaction between DNA and cationic polymers has recently attracted more attention in the nonviral DNA delivery field, the literature on the effect of varying polycation charge density on DNA-cationic polymer complexation is still scarce. Thus, the aim of this study was to systematically assess the influence of the degree of ionization of a weak cationic polyelectrolyte (poly[2-(dimethylamino)ethyl methacrylate] or DMAEMA homopolymer) on its ability to form complexes with DNA. This was achieved by varying the solution pH from 4.0 to 8.0 and analyzing the resulting effects on the binding affinity, thermodynamic properties, complex size, and morphology. Lowering the solution pH led to higher degrees of ionization for the cationic polymer and hence greater binding affinities with DNA, as judged by the increased propensity of the former to displace ethidium bromide from DNA and also by relatively low monomer:nucleotide molar ratio (0.8:1) required to retard the migration of free DNA. Isothermal titration microcalorimetry studies further confirmed that a stronger interaction occurred at low pH than at high pH. By decreasing the pH from 8.0 to 6.6, K(obs) increased from 7.8 x 10(5) to 20.4 x 10(5) M(-1). More efficient condensation at low pH was demonstrated by the reduction of ethidium bromide fluorescence in the loading wells from gel electrophoresis, decreased complex sizes without agglomeration occurring at high polymer/DNA ratios, together with discrete and dense spherical complexes observed in TEM studies. This may be attributed to the presence of electrostatic stabilization from excess cationic polymer chains, which provide a repulsive shell around the polymer/DNA complex. The physicochemical data indicate that the increased degree of ionization for the DMAEMA homopolymer at lower pH results in higher binding affinity, smaller and more compact complexes, and more efficient condensation. These findings therefore highlight the importance of the degree of ionization on DNA complex formation for weak cationic polyelectrolytes.

The intranasal route of administration provides a noninvasive method to deliver drugs into the systemic circulation and/or directly into the brain. Direct nose-to-brain drug delivery offers the possibility to treat central nervous system diseases more effectively, as it can evade the blood-brain barrier. In vitro and ex vivo intranasal models provide a means to investigate physiological and pharmaceutical factors that could play a role in drug delivery across the nasal epithelium as well as to determine the mechanisms involved in drug absorption from the nose. The development and implementation of cost-effective pharmacokinetic models for intranasal drug delivery with good in vitro-in vivo correlation can accelerate pharmaceutical drug product development and improve economic and ecological aspects by reducing the time and costs spent on animal studies. Special considerations should be made with regard to the purpose of the in vitro/ex vivo study, namely, whether it is intended to predict systemic or brain delivery, source and site of tissue or cell sampling, viability window of selected model, and the experimental setup of diffusion chambers. The type of model implemented should suit the relevant needs and requirements of the project, researcher, and interlaboratory. This review aims to provide an overview of in vitro and ex vivo models that have been developed to study intranasal and direct nose-to-brain drug delivery., (© 2023 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons Ltd.)

PEGylated polyamidoamine (PAA) polymers were investigated for the production of sterically stabilised DNA delivery systems. Comparison of a PEGylated polymer (NG47) with a non-PEGylated polymer (NG49) showed similar binding of co-polymer to DNA by displacement of ethidium bromide (EB) and DNA melting studies. Gel electrophoresis, turbidimetric analysis and PCS demonstrated differences in the colloidal properties of the complexes, which were attributable to the formation of soluble complexes by the PEGylated co-polymer. However, transmission electron microscopy (TEM) showed that the resulting complexes containing poly(ethylene glycol) (PEG) were not well condensed, susceptible to degradation by nucleases, and thus not suited for in vivo delivery. The poor properties of the PEGylated co-polymer were attributed to an excess of PEG. However, polymer blends of NG47 and NG49 at defined ratios of polymer to co-polymer and total repeating units (RUs) to nucleotide, spontaneously formed complexes with a range of desirable properties. These included small size and polydispersity, high particle density, low surface charge and resistance to nuclease degradation. Complexes made with PEGylated polymer alone, and the polymer blends both suffered from a reduced polyfection activity. This was attributed to a low surface charge on the complex, which reduced interactions with the cell membrane and consequent uptake of the particles into the cell.

While covalent attachment of small drug molecules to AB copolymers for the formation of polymeric micelles for drug delivery has been investigated, few studies have focused on non-covalent interactions. The aim of this study was therefore to explore the potential of non-covalent interactions between an AB copolymer, Poly(aspartic acid)-poly(ethylene glycol) (Pasp-PEG), with anionic pendant groups and diminazene aceturate, a small molecular weight cationic drug. Micelles were prepared by mixing solutions of Pasp-PEG and diminazene in 25 mM Tris-HCl buffer. At all Pasp-PEG concentrations studied, the micelles appeared to be water soluble with a unimodal size distribution and ranged in size from approximately 22 to 60 nm. The polyionic micelles also displayed similar and small absolute zeta potential values at various drug:monomer molar ratios which confirmed stabilisation by the PEG corona. The scattering intensity was maximal and remained unchanged, while particle size increased slightly at pH range from 3.4 to 7.2. At this pH range both the polymer and drug would be ionised and ionic interactions possible to drive micellar formation. An increase in size and scattering intensity with addition of NaCl to the micelles was attributed to dehydration of the PEG corona which may have led to aggregation of the micelles. The absence of micellar dissociation upon addition of salt was attributed to the dominance of hydrogen bonding between Pasp and diminazene aceturate, as assessed by isothermal titration microcalorimetry. Morphological evaluation of these constructs showed them to be discrete and fairly uniform in size and shape. This study was therefore successful in confirming the potential of non-covalent interactions using an AB copolymer to form polyionic micelles for drug delivery.

The current research work aims to study the pharmacokinetic and nasal ciliotoxicity of donepezil liposome-based in situ gel to treat Alzheimer's disease. The physicochemical properties and first-pass metabolism of donepezil HCl result in low concentrations reaching the brain post oral administration. To overcome this problem, donepezil HCl-loaded liposomes were formulated using the ethanol injection method. The donepezil HCl-loaded liposomes were spherical with a size of 103 ± 6.2 nm, polydispersity index of 0.108 ± 0.008, and entrapment efficiency of 93 ± 5.33 %. The optimized in situ gel with donepezil HCl-loaded liposomes showed 80.11 ± 7.77 % drug permeation than donepezil HCl solution-based in situ gel (13.12 ± 4.84 %) across sheep nasal mucosa. The nasal ciliotoxicity study indicated the safety of developed formulation for administration via nasal route. The pharmacokinetics and biodistribution study of developed formulation showed higher drug concentration (1239.61 ± 123.60 pg/g) in the brain after nasal administration indicating its better potential via the nasal pathway. To treat Alzheimer's disease, the administration of liposome-based in situ gel through the nasal pathway can therefore be considered as an effective and promising mode of drug delivery., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Neuroinflammation (NIF) plays an essential role in the pathology of neurological disorders like Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy. Despite progress in the drug discovery and development of new drugs, drug delivery to the central nervous system (CNS) still represents the challenge due to the presence of the blood-brain barrier (BBB). Targeting NIF may require an adequate amount of drug to cross the BBB. Recently, the intranasal (IN) drug administration has attracted increasing attention as a reliable method to cross the BBB and treat neurological disorders. On the other hand, using optimized nanoparticles may improve the IN delivery limitations, increase the mucoadhesive properties, and prevent drug degradation. NPs can carry and deliver drugs to the CNS by bypassing the BBB. In this review, we described briefly the NIF as a pathologic feature of CNS diseases. The potential treatment possibilities with IN transfer of NP-loaded drugs will enhance the establishment of more efficient nanoformulations and delivery systems., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neurodegenerative diseases like Alzheimer's disease require treatment where it is essential for drug to reach brain. Nose to brain delivery of drugs enables direct transport to brain bypassing blood brain barrier. Imatinib mesylate, an anti-cancer agent, was found to have potential anti-Alzheimer's activity and thus repurposed for the same. However, the drug has severe side effects, poor brain bioavailability which may hinder effective treatment of Alzheimer's disease. In the current work, imatinib mesylate-loaded liposomes were prepared with particle size below 150 nm with sustained drug release up to 96 h. The liposomal drug formulation was compared with plain drug solution for cytotoxicity on N2a cells and did not show any kind of toxicity at concentrations up to 25 μg/mL. The nanocarrier formulation was then evaluated for brain deposition by nose to brain administration in comparison with drug solution in rats. The liposomes effectively improved the brain deposition of drug in brain from formulation compared to pure drug solution as indicated by AUC from in vivo experiments. These results indicate that the nose to brain delivery of liposomal imatinib mesylate improved the drug deposition and residence time in brain compared to drug solution administered through oral and intranasal routes.

The first step in the development of Helicobacter pylori pathogenicity is the receptor-mediated adhesion to the gastric epithelium. Inhibition of outer membrane proteins of H. pylori (e.g. BabA) by antiadhesive drugs will contribute to reduced recolonization and infection. Pectin from apple inhibits the BabA and LPS-mediated adhesion of H. pylori to human stomach cells. Pectin-coated liposomes with encapsulated amoxicillin were characterized for polydispersity, zeta potential, encapsulation efficiency, stability, and amoxicillin release. Coated liposomes did not influence the viability of AGS and HT29-MTX cells up to 100 μg/mL but exert cytotoxicity against H. pylori at 10 μg/mL. Pectin-coating of liposomes provoked direct interaction and subsequent binding of the particles to surface structures of H. pylori, and interaction with mucus from porcine stomach and mucus secreted by HT29-MTX cells. Laser scanning microscopy of H. pylori and AGS cells together with liposomes indicated co-aggregation. The mucoadhesive effect seems interesting as stomach cells are covered by a mucus layer. H. pylori is able to penetrate and cross the mucin rapidly to reach pH-neutral epithelium to escape the acidic environment, followed by interaction with epithelial cells. In summary, all experimental evidence is consistent with a specific interaction of pectin-coated liposomes with mucins and surface structures of H. pylori. As the coated liposomes show mucoadhesion to the negatively charged mucins, docking to stomach mucin, mucus penetration, and recognition of and adhesion to H. pylori, they can be considered a novel type of multifunctional drug carriers for local antibiotic therapy against H. pylori. KEY POINTS: • Smart, multifunctional mucoadhesive liposomes • Specific targeting against BabA/LPS of Helicobacter pylori • Inhibition of bacterial adhesion of H. pylori to human host cells • Release of antibiotic cargo.

The purpose of this study was to construct and characterize iron oxide nanoparticles (IONP CO ) for intracellular delivery of the anthracycline doxorubicin (DOX; IONP DOX ) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONP DOX within 24 h (100% at 70 h). Efficient internalization of IONP DOX and IONP CO in HeLa cells occurred through pino- and endocytosis, with both IONP accumulating in a perinuclear pattern. IONP CO were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL IONP CO . Treatment with IONP DOX resulted in a concentration- and time-dependent decrease in cell proliferation (IC 50  = 27.5 ± 12.0 μg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONP CO (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONP DOX efficiently delivered DOX resulting in increased cell death vs IONP CO .

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes 1,2 , yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications 3-5 . Compared with subcutaneously administered drugs, oral formulations create less patient discomfort 4 , show greater chemical stability at high temperatures 6 , and do not generate biohazardous needle waste 7 . An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract 8 . We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.

The shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (T g ) or melting (T m )], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m -1 , material-water interfacial tension <6 mN m -1 ), especially if the nanoparticles are soft (<1 GPa), rough (R rms > 10 nm), porous (>1 m 2 g -1 ), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Oral application of therapeutic enzymes is a promising and non-invasive administration that improves patient compliance. However, the gastrointestinal tract poses several challenges to the oral delivery of proteins, including harsh pH conditions and digestive proteases. A promising way to stabilise enzymes during their gastrointestinal route is by modification with polymers that can provide both steric shielding and selective interaction in different digestive compartments. We give an overview of modification technologies for oral enzymes ranging from functionalisation of native proteins, to site-specific mutation and protein-polymer engineering. We specifically focus on enzymes that are active directly in the gastrointestinal lumen and not systemically absorbed. In addition, we discuss examples of microparticle and nanoparticle encapsulated enzymes for improved oral delivery. The modification of orally administered enzymes offers a broad chemical variability and may be a promising tool for enhancing their gastrointestinal stability.

Abstract: To exert its activity a drug must reach its pharmacological site(s) of action(s) within the body. One of the current approaches to achieve site specific delivery utilises the use of a carrier. This review focuses on the physicochemical and biological properties of polymeric particulate carriers in the nanometre size range surface modified by poly(ethylene oxide) (PEO). Such systems are able to bypass the normal physiological defence processes occurring after the intravenous injection of particulates and, depending on the particle size and PEO layer properties, remain for a prolonged period of time in the systemic circulation, or have a degree of selectivity for sites of deposition within the body. [Copyright &y& Elsevier]

Alzheimer's disease (AD) is one of the most common diseases of the central nervous system in the middle-aged and elderly population. It is a neurodegenerative disorder, and its main clinical symptoms include the loss of established memories, a decline in learning capacity, and the buildup of β-amyloid peptides. The disease is often accompanied by neurodegenerative changes and the formation of neurofibrillary tangles. However, the number of drugs available for the clinical treatment of AD remains limited. Currently, existing medications are not effective in completely curing the disease or stopping its progression. Due to their excellent biocompatibility and biodegradability, polymers have been widely used as drug delivery carriers in various fields including cancer therapy and wound healing. The use of polymers enables targeted drug delivery and prolonged release profiles. In recent years, researchers have made significant progress in utilizing polymers such as polyethylene glycol, poly (lactic-co-glycolic acid) (PLGA), and chitosan (CS) to deliver drugs and blood-brain barrier receptor ligands for the treatment of AD. Moreover, many polymers with inherent therapeutic properties have been developed, including the already marketed GV-971 as well as experimental polymers such as PLGA and CS oligosaccharide. This review summarizes the applications of polymers in AD treatment over the past few years and highlights their current limitations to help researchers better understand current advancements in polymer development and identify future research directions. [ABSTRACT FROM AUTHOR]

Nanomedicine, the most promising approach for regulated and targeted drug delivery, is frequently applied in cancer treatment. Essentially, accumulating evidence indicates that nanomedicine has positive results in the treatment of breast cancer (BC), with many BC patients benefiting from nanomedicine-related treatments. Currently, nanodrug delivery systems based on stimulus responses are gaining popularity because of their additional ability to manage drug release depending on the interior environment of the cancer. This review includes a synopsis of several types of internal (pH, redox, enzyme, reactive oxygen species, and hypoxia) stimuli-responsive nanoparticle drug delivery systems as well as perspectives for forthcoming times. Stimulus-responsive nanoparticles can remain stable under physiological conditions while being rapidly activated to release drugs in response to specific stimuli, prolonging blood circulation and increasing cancer cellular uptake, resulting in excellent therapeutic performance and improved biosafety. In this paper, we discuss tumor microenvironment responsive Nanoformulation for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Chitosan (CS) derivatives have been extensively investigated to enhance the physicochemical and biological properties of CS, such as its solubility, biocompatibility, and bioactivity, which are required in various areas of pharmacy and medicine. The present work emphasizes the ongoing research and development in this field, suggesting that the further exploration of CS derivatives could lead to innovative solutions that benefit society. The physicochemical properties, biological activities, methods of preparation, advantages, limitations, intended application areas, and realized practical implementations of particular CS derivatives are summarized and discussed herein. Despite the numerous promising attributes of CS derivatives as reported in this paper, however, challenges like target selectivity, standardization (purity, chitosan structural variability), and cost-effectiveness still need addressing for widespread implementation, especially in drug delivery. Therefore, basic research studies still prevail in CS drug delivery systems. However, for specific applications such as wound healing and tissue engineering, implementations of CS derivatives in practice are found to be more frequent. To obtain a more complex view of the topic, information from the scientific papers reviewed is supplemented with information from actual patents and clinical studies. Both basic research advances and the most successful and important medical implementations of CS derivatives are discussed concerning further challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment. [ABSTRACT FROM AUTHOR]

Spatiotemporally controlled cargo release is a key advantage of nanocarriers in anti-tumor therapy. Various external or internal stimuli-responsive nanomedicines have been reported for their ability to increase drug levels at the diseased site and enhance therapeutic efficacy through a triggered release mechanism. Redox-manipulating nanocarriers, by exploiting the redox imbalances in tumor tissues, can achieve precise drug release, enhancing therapeutic efficacy while minimizing damage to healthy cells. As a typical redox-sensitive bond, the disulfide bond is considered a promising tool for designing tumor-specific, stimulus-responsive drug delivery systems (DDS). The intracellular redox imbalance caused by tumor microenvironment (TME) regulation has emerged as an appealing therapeutic target for cancer treatment. Sustained glutathione (GSH) depletion in the TME by redox-manipulating nanocarriers can exacerbate oxidative stress through the exchange of disulfide-thiol bonds, thereby enhancing the efficacy of ROS-based cancer therapy. Intriguingly, GSH depletion is simultaneously associated with glutathione peroxidase 4 (GPX4) inhibition and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization, triggering mechanisms such as ferroptosis and cuproptosis, which increase the sensitivity of tumor cells. Hence, in this review, we present a comprehensive summary of the advances in disulfide based redox-manipulating nanocarriers for anticancer drug delivery and provide an overview of some representative achievements for combinational therapy and theragnostic. The high concentration of GSH in the TME enables the engineering of redox-responsive nanocarriers for GSH-triggered on-demand drug delivery, which relies on the thiol-disulfide exchange reaction between GSH and disulfide-containing vehicles. Conversely, redox-manipulating nanocarriers can deplete GSH, thereby enhancing the efficacy of ROS-based treatment nanoplatforms. In brief, we summarize the up-to-date developments of the redox-manipulating nanocarriers for cancer therapy based on DDS and provide viewpoints for the establishment of more stringent anti-tumor nanoplatform. [ABSTRACT FROM AUTHOR]

Nowadays, the interest in research towards the local administration of drugs via the inhalation route is growing as it enables the direct targeting of the lung tissue, at the same time reducing systemic side effects. This is of great significance in the era of nucleic acid therapeutics and personalized medicine for the local treatment of severe lung diseases. However, the success of any inhalation therapy is driven by a delicate interplay of factors, such as the physiochemical profile of the payload, formulation, inhalation device, aerodynamic properties, and interaction with the lung fluids. The development of drug delivery systems tailored to the needs of this administration route is central to its success and to revolutionize the treatment of respiratory diseases. With this review, we aim to provide an up-to-date overview of advances in the development of nanoparticulate carriers for drug delivery to the lung tissue, with special regard concerning lipid and polymer-based nanocarriers (NCs). Starting from the biological barriers that the anatomical structure of the lung imposes, and that need to be overcome, the current strategies to achieve efficient lung delivery and the best support for the success of NCs for inhalation are highlighted. [ABSTRACT FROM AUTHOR]

Nanoscale drug delivery systems (nDDS) have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects. Although several nDDS have been successfully approved for clinical use up to now, biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment. Polyethylene glycol (PEG)-modification (or PEGylation) has been regarded as the gold standard for stabilising nDDS in complex biological environment. However, the accelerated blood clearance (ABC) of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications. Zwitterionic polymer, a novel family of anti-fouling materials, have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility. Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues. More impressively, zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution, pressure gradients, impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications. The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS, which could facilitate their better clinical translation. Herein, we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlying mechanisms. Finally, prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment. [ABSTRACT FROM AUTHOR]

Several therapeutic agents are used for controlling brain diseases, but they are not successfully reaching target sites due to the complex nature of the brain. Nasal administration as an alternate administration route has been proposed for brain targeting. To solve the above limitation linked to brain targeting through the transmission of nasal products, encourage the production of novel drug delivery by the combination of nanotechnology. The present review focuses on the latest understanding of pathways underlying central nervous system intranasal transmission. Novel Drug delivery systems as important methods for targeting the brain without toxicity in the nasal mucosa and central nervous system, they have acquired the capacity of CNS. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan–DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Poly-γ-glutamic acid (γ-PGA) is a natural polymer composed of glutamic acid monomer and it has garnered substantial attention in both the fields of material science and biomedicine. Its remarkable cell compatibility, degradability, and other advantageous characteristics have made it a vital component in the medical field. In this comprehensive review, we delve into the production methods, primary application forms, and medical applications of γ-PGA, drawing from numerous prior studies. Among the four production methods for PGA, microbial fermentation currently stands as the most widely employed. This method has seen various optimization strategies, which we summarize here. From drug delivery systems to tissue engineering and wound healing, γ-PGA's versatility and unique properties have facilitated its successful integration into diverse medical applications, underlining its potential to enhance healthcare outcomes. The objective of this review is to establish a foundational knowledge base for further research in this field. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPs' uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect. [ABSTRACT FROM AUTHOR]

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers' act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine's low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor's effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma's rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect. [ABSTRACT FROM AUTHOR]

The role of nanotechnology in the diagnostics and therapeutics of diabetes has been widely known. In this paper, the authors have tried to comprehensively cover the recent advances in this field. After giving a brief account of diabetes and the limitations of the current anti-diabetic regime, the authors have discussed nanoparticle-based drug delivery systems for diabetes, quality and safety evaluation parameters of nano-based anti-diabetic therapeutics, and the limitations of conventional anti-diabetic therapies overcome by nanotechnology. This article also discusses the clearance mechanisms and toxicity concerns of NPs based on anti-diabetic drugs. The authors have summarized the current trends and suggested future directions for nanotechnology. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effect of Moringa oleifera nanoparticles (MoNP) supplementation based on the Self Nano Emulsifying Drug Delivery System on insulin resistance in prediabetes models. Twenty-five Rattus norvegicus were split into five groups, containing five rats each: normal control group (given a standard diet), as well as a prediabetes control group and three intervention groups fed a high-fat diet for four weeks. Those with fasting blood serum (FBS) ranged betwen 100-130 mg/dL were deemed prediabetic. The intervention groups were then given MoNP at dosages of 75, 125, and 225 mg/kg bw, respectively, whereas the normal and prediabetic groups received a regular diet. FBS, fasting insulin, TNF-α, IL-6, triglycerides, and HOMA-IR were all examined after treatment. MoNP significantly reduced TNF-α, IL-6, triglycerides, and HOMA-IR levels (p<0.05). It also generated a considerable rise in insulin levels in contrast to the prediabetic control group (p<0.05). Supplementation of MoNP at the lowest dose of 75 mg/kg body weight was able to lower FBS to normal levels from 130.04 mg/dL to 97.34 mg/dL and reduce HOMA-IR from 4.20 to 3.71 (p < 0.05). The administration of MoNP can reduce inflammatory cytokines and insulin resistance in the prediabetes model. [ABSTRACT FROM AUTHOR]

Obesity has reached an epidemic proportion in the last thirty years, and it is recognized as a major health issue in modern society now with the possibility of serious social and economic consequences. By the year 2030, nearly 60% of the global population may be obese or overweight, which emphasizes a need for novel obesity treatments. Various traditional approaches, such as pharmacotherapy and bariatric surgery, have been utilized in clinical settings to treat obesity. However, these methods frequently show the possibility of side effects while remaining ineffective. There is, therefore, an urgent need for alternative obesity treatments with improved efficacy and specificity. Polymeric materials and chemical strategies are employed in emerging drug delivery systems (DDSs) to enhance therapy effectiveness and specificity by stabilizing and controlling the release of active molecules such as natural ingredients. Designing DDSs is currently a top priority research objective with an eye towards creating obesity treatment approaches. In reality, the most recent trends in the literature demonstrate that there are not enough in-depth reviews that emphasize the current knowledge based on the creation and design of DDSs for obesity treatment. It is also observed in the existing literature that a complex interplay of different physical and chemical parameters must be considered carefully to determine the effectiveness of the DDSs, including microneedles, for obesity treatment. Additionally, it is observed that these properties depend on how the DDS is synthesized. Although many studies are at the animal-study stage, the use of more advanced DDS techniques would significantly enhance the development of safe and efficient treatment approaches for obese people in the future. Considering these, this review provides an overview of the current anti-obesity treatment approaches as well as the conventional anti-obesity therapeutics. The article aims to conduct an in-depth discussion on the current trends in obesity treatment approaches. Filling in this knowledge gap will lead to a greater understanding of the safest ways to manage obesity. [ABSTRACT FROM AUTHOR]

Synthetic polypeptides are biocompatible and biodegradable macromolecules whose composition and architecture can vary over a wide range. Their unique ability to form secondary structures, as well as different pathways of modification and biofunctionalization due to the diversity of amino acids, provide variation in the physicochemical and biological properties of polypeptide-containing materials. In this review article, we summarize the advances in the synthesis of polypeptides and their copolymers and the application of these systems for drug delivery in the form of (nano)particles or hydrogels. The issues, such as the diversity of polypeptide-containing (nano)particle types, the methods for their preparation and drug loading, as well as the influence of physicochemical characteristics on stability, degradability, cellular uptake, cytotoxicity, hemolysis, and immunogenicity of polypeptide-containing nanoparticles and their drug formulations, are comprehensively discussed. Finally, recent advances in the development of certain drug nanoformulations for peptides, proteins, gene delivery, cancer therapy, and antimicrobial and anti-inflammatory systems are summarized. [ABSTRACT FROM AUTHOR]

Nanocarriers have been extensively developed in the biomedical field to enhance the treatment of various diseases. However, to effectively deliver therapeutic agents to desired target tissues and enhance their pharmacological activity, these nanocarriers must overcome biological barriers, such as mucus gel, skin, cornea, and blood-brain barriers. Polysaccharides possess qualities such as excellent biocompatibility, biodegradability, unique biological properties, and good accessibility, making them ideal materials for constructing drug delivery carriers. Nanogels, as a novel drug delivery platform, consist of three-dimensional polymer networks at the nanoscale, offering a promising strategy for encapsulating different pharmaceutical agents, prolonging retention time, and enhancing penetration. These attractive properties offer great potential for the utilization of polysaccharide-based nanogels as drug delivery systems to overcome biological barriers. Hence, this review discusses the properties of various barriers and the associated constraints, followed by summarizing the most recent development of polysaccharide-based nanogels in drug delivery to overcome biological barriers. It is expected to provide inspiration and motivation for better design and development of polysaccharide-based drug delivery systems to enhance bioavailability and efficacy while minimizing side effects. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly aggressive malignant tumor, and the most prevalent primary malignant tumor affecting the brain and central nervous system. Recent research indicates that the genetic profile of GBM makes it resistant to drugs and radiation. However, the main obstacle in treating GBM is transporting drugs through the blood–brain barrier (BBB). Albumin is a versatile biomaterial for the synthesis of nanoparticles. The efficiency of albumin-based delivery systems is determined by their ability to improve tumor targeting and accumulation. In this review, we will discuss the prevalence of human glioblastoma and the currently adopted treatment, as well as the structure and some essential functions of the BBB, to transport drugs through this barrier. We will also mention some aspects related to the blood–tumor brain barrier (BTBB) that lead to poor treatment efficacy. The properties and structure of serum albumin were highlighted, such as its role in targeting brain tumors, as well as the progress made until now regarding the techniques for obtaining albumin nanoparticles and their functionalization, in order to overcome the BBB and treat cancer, especially human glioblastoma. The albumin drug delivery nanosystems mentioned in this paper have improved properties and can overcome the BBB to target brain tumors. [ABSTRACT FROM AUTHOR]

Background: Emulsomes are a type of lipid-based nanoparticle that consists of a solid lipid core surrounded by a phospholipid bilayer and have shown promise as drug delivery systems for a variety of applications. The major advantageous aspect of employing lipid-based carriers is their ability to enhance the solubility and bioavailability of poorly water-soluble drugs, mandatorily in case of intranasal drug delivery. These structures have portrayed significant ability to encapsulate drug with poor water solubility and low oral bioavailability, further leading to a completely enhanced drug delivery systems for achieving stability and controlled release of drug. The selection of lipid components and their physiochemical properties can be tailored to optimize drug solubility, blood brain barrier permeability, and enhanced targeting. Intranasal drug delivery systems offer several advantages over other routes of administration. Intranasal delivery of drugs can provide rapid and efficient absorption into the bloodstream, bypassing first-pass metabolism in the liver and potentially reducing the risk of systemic side effects. Nasal mucosa comprises of dense network of blood vessels, that allow much enhanced rapid drug absorption and direct systemic delivery once the medication is being insufflated through the nasal route. Emulsomes can be used to encapsulate a wide range of drugs, including hydrophobic compounds that are difficult to formulate using traditional delivery methods. By incorporating targeting ligands or other components into the emulsome structure, it is possible to create formulations that are highly selective for specific tissues or cells. The characterization parameters majorly particle size, zeta potential, and encapsulation efficiency play a significant role while demonstrating the effectiveness of emulsome formulation and further its nasal route of administration. Therefore, by assessing and evaluating the parameters, researchers could effectively gain insights into the quality, stability, and enhanced therapeutic effects of emulsome drug carrier, leading to impactful information which would help in future intranasal emulsome preparation preparations, optimization and ensuring the overall effectiveness of the drug delivery systems. Short conclusion: This review discusses the idea of emulsomes drug delivery systems, reviews the effectiveness of emulsomes for the delivery of small molecules, and pays particular attention to its structural and formulation design including benefits of intranasal emulsome delivery with recent advancements, stability aspects, and various considerations related to drug delivery and comprising of future prospects. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop an innovative gallic-acid (GA) drug delivery system that could be administered transdermally, resulting in enhanced therapeutic benefits and minimal negative consequences. The method employed involved the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with GA through nanoprecipitation-denoted GA@PLGANPs. The results reveal that this strategy led to perfectly spherical, homogeneous, and negatively charged particles, which are suitable for administration via skin patches or ointments. A further analysis indicates that these GA@PLGANPs exhibit remarkable antioxidant activity as well as potent antibacterial effects against a diverse range of microorganisms, making them ideal candidates for numerous applications. Additionally, it has been observed that these nanoparticles can effectively mitigate oxidative stress while also significantly inhibiting microbial growth by exerting detrimental effects on bacterial cell walls or membranes. In conclusion, on the basis of the findings presented in this study, there is strong evidence supporting the potential use of GA@PLGANPs as an effective therapy option with reduced side effects compared to conventional drug delivery methods. [ABSTRACT FROM AUTHOR]

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review. [ABSTRACT FROM AUTHOR]

Cancer is still one of the leading causes of death worldwide. Nanotechnology, particularly nanoparticle-based platforms, is at the leading edge of current cancer management research. Polymer-based nanosystems have piqued the interest of researchers owing to their many benefits over other conventional drug delivery systems. Polymers derived from both natural and synthetic sources have various biomedical applications due to unique qualities like porosity, mechanical strength, biocompatibility, and biodegradability. Polymers such as poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polyethylene glycol (PEG) have been approved by the USFDA and are being researched for drug delivery applications. They have been reported to be potential carriers for drug loading and are used in theranostic applications. In this review, we have primarily focused on the aforementioned polymers and their conjugates. In addition, the therapeutic and diagnostic implications of polymer-based nanosystems have been briefly reviewed. Furthermore, the safety of the developed polymeric formulations is crucial, and we have discussed their biocompatibility in detail. This article also discusses recent developments in block co-polymer-based nanosystems for cancer treatment. The review ends with the challenges of clinical translation of polymer-based nanosystems in drug delivery for cancer therapy. [ABSTRACT FROM AUTHOR]