Formation of the so-called organic-inorganic nanohybrid material was exploited for the preparation of a controlled release formulation. The inorganic Zn-Al-layered double hydroxide (LDH) was used as a matrix, hosting an active agent or a guest, alpha-naphthaleneacetate (NAA), a plant growth regulator by self-assembly technique. The reverse process, i.e., the deintercalation or release of the guest, NAA was found to be rapid initially, followed by a more sustained release thereafter and this behavior was dependent on the pH of the release medium, the aqueous solution. The mechanism of release has been interpreted on the basis of the ion-exchange process between the NAA anion intercalated in the lamella host and nitrate or hydroxyl anions in the aqueous solution.
Macromolecular protein and peptide therapeutics have been proven to be effective in treating critical human diseases precisely. Thanks to biotechnological advancement, a huge number of proteins and peptide therapeutics were made their way to pharmaceutical market in past few decades. However, one of the biggest challenges to be addressed for protein therapeutics during clinical application is their fast degradation in serum and quick elimination owing to enzymatic degradation, renal clearance, liver metabolism and immunogenicity, attributing to the short half-lives. Size and hydrophobicity of protein molecules make them prone to kidney filtration and liver metabolism. On the other hand, proteasomes responsible for protein destruction possess the capability of specifically recognizing almost all kinds of foreign proteins while avoiding any unwanted destruction of cellular components. At present almost all protein-based drug formulations available in market are administered intravenously (IV) or subcutaneously (SC) with high dosing at frequent interval, eventually creating dose-fluctuation-related complications and reducing patient compliance vastly. Therefore, artificially increasing the therapeutic half-life of a protein by attaching to it a molecule that increases the overall size (eg, PEG) or helps with receptor mediated recycling (eg, albumin), or manipulating amino acid chain in a way that makes it more prone towards aggregate formation, are some of the revolutionary approaches to avoid the fast degradation in vivo. Half-life extension technologies that are capable of dramatically enhancing half-lives of proteins in circulation (2-100 folds) and thus improving their overall pharmacokinetic (PK) parameters have been successfully applied on a wide range of protein therapeutics from hormones and enzymes, growth factor, clotting factor to interferon. The focus of the review is to assess the technological advancements made so far in enhancing circulatory half-lives and improving therapeutic potency of proteins.
The established cancer treatment strategy in clinical setting is based on chemo and radiation therapy, having limitations due to severe side-effects and drug-resistance. Small molecule chemo-drugs target any fast-dividing cells irrespective of healthy or defective origin. As a result, a substantial amount of healthy tissue is also destroyed. Moreover, failure to recognize the heterogeneity of tumour tissue results in drug-resistance over the course of time. On the other hand, peptides and proteins actively target somatic changes that are signature to any specific tumour tissue. Development and metastasis of cancer cells require unique disruption/alteration of protein activity. Identification of those wild and cancerous genotypes and phenotypes is the key to establishing easy 'targets' for protein based targeted therapeutics. The approach is cytostatic and tissue specific, which reduces drug toxicity. Biopharmaceutical products based on proteins and peptides are slowly re-directing oncology from cytotoxic small molecular treatment approach to target oriented cytostatic strategy. This review focuses on current and upcoming peptide and protein-based precision therapeutics. At the same time, the study also shades light on the technological advancement in the field of protein and peptide-based therapeutics.
The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.
Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described.
The influence of microwave irradiation on the drug release properties of freshly prepared and aged alginate, alginate-chitosan and chitosan beads was investigated. The beads were prepared by extrusion method with sulphathiazole as a model drug. The dried beads were subjected to microwave irradiation at 80 W for 10 min, 20 min or three consecutive cycles of 10 and 20 min, respectively. The profiles of drug dissolution, drug content, drug stability, drug polymorphism, drug-polymer interaction, polymer crosslinkage and complexation were determined by dissolution testing, drug content assay, differential scanning calorimetry and Fourier transform infra-red spectroscopy. The chemical stability of drug embedded in beads was unaffected by microwave conditions and length of storage time. The release property of drug was mainly governed by the extent of polymer interaction in beads. The aged alginate beads required intermittent cycles of microwave irradiation to induce drug release retarding effect in contrast to their freshly prepared samples. Unlike the alginate beads, the level of polymer interaction was higher in aged alginate-chitosan beads than the corresponding fresh beads. The drug release retarding property of aged alginate-chitosan beads could be significantly enhanced through subjecting the beads to microwave irradiation for 10 min. No further change in drug release from these beads was observed beyond 30 min of microwave irradiation. Unlike beads containing alginate, the rate and extent of drug released from the aged chitosan beads were higher upon treatment by microwave in spite of the higher degree of polymer interaction shown by the latter on prolonged storage. The observation suggested that the response of polymer matrix to microwave irradiation in induction of drug release retarding property was largely affected by the molecular arrangement of the polymer chains.
Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.
Controlled release fertilizer (CRF) plays a crucial yet necessary part in the sustainable agriculture industry. An alarming rise in call for crop production directly influences the increasing need for synthetically derived fertilizers and pesticides production. The application of CRF has been a gamechanger as an environmentally sustainable pathway to increase crop yields by paving desired phase of plant growth via a direct or indirect mechanism. The mechanism of CRF does not only decreases nutrient dissipation due to volatilization and leaching, but also provides a precisely appropriate nutrient release design that is suitable in the physiological and biochemical aspect of the plant growth. However, CRF is not deployed on larger scale of commercial agriculture practices due to being expensive, has relatively low efficiency in releasing nutrients and its coatings are largely composed of petroleum-based synthetic polymers. Alternatively, there are many polymers derived from renewable and biodegradable sources that can be used as coating material for CRF in the form of bio-nanocomposites. Having said that, there is an apparent gap between the mechanism of the CRFs for promoting plant growth and the prominent role of the nanocomposites especially bio-nanocomposites as coating material for CRF synthesis, thus the importance of nanotechnology application in enhancing the effectiveness of CRF. Therefore, this review attempts to bridge the stated gap and summarizes the comprehensive developments, application mechanisms and future potential of CRF as a fertilizer for crop sustainability.
Aptamers are a class of folded nucleic acid strands capable of binding to different target molecules with high affinity and selectivity. Over the years, they have gained a substantial amount of interest as promising molecular tools for numerous medical applications, particularly in targeted therapeutics. However, only the different treatment approaches and current developments of aptamer-drug therapies have been discussed so far, ignoring the crucial technical and functional aspects of constructing a therapeutically effective aptamer-driven drug delivery system that translates to improved in-vivo performance. Hence, this paper provides a comprehensive review of the strategies used to improve the therapeutic performance of aptamer-guided delivery systems. We focus on the different functional features such as drug deployment, payload capacity, in-vivo stability and targeting efficiency to further our knowledge in enhancing the cell-specific delivery of aptamer-drug conjugates. Each reported strategy is critically discussed to emphasize both the benefits provided in comparison with other similar techniques and to outline their potential drawbacks with respect to the molecular properties of the aptamers, the drug and the system to be designed. The molecular architecture and design considerations for an efficient aptamer-based delivery system are also briefly elaborated.
E. coli mediated gene delivery faces a major drawback of low efficiency despite of being a safer alternative to viral vectors. This study showed a novel, simple and effective strategy to enhance invasive E. coli DH10B vector's efficiency in human epithelial cells. The bactofection efficiency of invasive E .coli vector was analyzed in nine cell lines. It demonstrated highest (16%) reporter gene (GFP) expression in cervical cells. Methods were employed to further enhance its efficiency by adding transfection reagents (trans-bactofection method) to promote entry into host cells, lysosomotropic reagents for escape from lysosomal degradation or antibiotics to lyse internalized bacteria. Increased bacterial entry, as elucidated from nil to 3% expression in liver cells, was obtained upon complexing bacteria with PULSin. Chloroquine mediated endosomal escape resulted in 7.2 folds increase whereas tetracycline addition to lyse internalized bacteria caused ≈90% of GFP in HeLa. Eventually, the combined effect of these three methods exhibited close to 100% GFP in cervical and remarkable increase of 138 folds in breast cells. This is the first study showing comparative study of vector's gene delivery ability in various epithelial cells of the human body with improving its delivery efficiency. These data demonstrated the potential of developed bactofection method to boost up the efficiency of other bacterial vectors also, which could further be used for effectual therapeutic gene delivery in human cells.
Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.
Cell impurities are an emerging nucleating molecular barriers having the capability in disordering the metabolic chain reactions of proteolysis, glycolysis and lipolysis. Their massive effects induced by copolymer crystal growth in compaction with metal and mineral transients are extended as well as in damaging DNA and mRNA structure motif and other molecular assembly e.g. histones structure unites. Their polycrystalline packing modes, polydispersity and their tendency to surface and interface adhesion prompted us in structuring scaffold biomaterials enriched with biopeptides, layered by phospho-glycerides ester-forms. The interface tension of the formed map is flexible and dependent to the surface exposure and its collapse modes to the surrounding molecular ligands. Thus, the attempts in increasing surface exposure e.g. the viscoelastic of structured lipopeptides and types of formed network structures interplays an extra- conjugating biomolecules having a least cytotoxicity effects to cells constituents. Disulfides molecules are selected to be the key regulatory element in rejoining both lipidic and proteic moieties by disordering atoms status via chemical ionization using organic catalyst. The insertion of methionine based peptidic chain at the lateral surfaces of scaffold biomaterials enhances the electron-meta-static motions by raising a molecular disordering status at distinct regions of the map e.g. epimerization into a nonpolar side that helps the chemical conjunction of disulfide groups with the esterified phosphoglycerides mono-layers. These effects in turn are accomplished by the formation of meso-sphere nonpolar- vesicles. The oxidation of disulfide group would alter the ordering of initial molecules by raising a newly molecular disorders to the map with high polarity to surface regions. In the same time indicates a continuation in the crystallization growth factor via a low chemical lesions between the impurities and a supersaturation in the intra-atomic distances with maximum cross linking to the deformed ligand with scaffold biomaterials.
Developing countries are consuming major part of the global urea production with an anticipated nitrogen use efficiency of 20 to 35%. The release of excess nitrogen in the soil is not only detrimental to the environment but also lessens the efficiency of the conventional urea. The urea performance can be enhanced by encapsulating it with slow release coating materials and synchronizing the nutrients' release with the plant up-taking. However, the present cost of most of the coated fertilizers is considerably higher than the conventional fertilizers. The high cost factor prevents their widespread use in mainstream agriculture. This paper documents a review of literature related to the global urea market, issues pertaining to the conventional urea use, natural and synthetic materials for slow release urea and fluidized bed spray coating process. The aim of the current review is to develop technical understanding of the conventional and non-conventional coating materials and associated spray coating mechanism for slow release urea production. The study also investigated the potential of starch as the coating material in relation to the coatings tested previously for controlled release fertilizers.
Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.
The recent designs of dynamic nanoassemblies exploiting the tumor-targeting properties have received increasing attention for tumor imaging and therapy due to their tumor-specific delivery and enhanced antitumor efficacy. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the nano-bio interactions in the tumor microenvironment (TME) remain poorly understood. This review aims to provide an overview of the development of tumor-responsive nanoassemblies towards the imaging, therapy and TME modulation in the tumor site. The tumor biology leading to TME formation and the potential TME properties for the practicable design of tumor-targeting nanoassemblies has been outlined. Furthermore, the various approaches for TME modification and the realization via dynamic nanoassemblies for enhanced tumor therapy were reviewed. Lastly, the prospects of these methods were briefly discussed. These strategies may inspire the development of new combinational cancer therapeutics.
Natural biopolymers have attracted considerable interest for the development of delivery systems for protein drugs owing to their biocompatibility, non-toxicity, renewability and mild processing conditions. This paper offers an overview of the current status and future perspectives of particle designs using biopolymers for the stabilization and controlled-delivery of a model protein drug--insulin. We first describe the design criteria for polymeric encapsulation and subsequently classify the basic principles of particle fabrication as well as the existing particle designs for oral insulin encapsulation. The performances of these existing particle designs in terms of insulin stability and in vitro release behavior in acidic and alkaline media, as well as their in vivo performance are compared and reviewed. This review forms the basis for future works on the optimization of particle design and material formulation for the development of an improved oral delivery system for protein drugs.
Graphene oxide (GO)-based nanocarriers have been frequently studied due to their high drug loading capacity. However, the unsatisfactory biocompatibility of these GO-based nanocarriers hampers their use in clinical settings. This review discusses how each of the physicochemical characteristics (e.g., size, surface area, surface properties, number of layers and particulate states) and surface coatings on GO affect its in vitro and in vivo nanotoxicity. We provide an overview on the effect of GO properties on interactions with cells such as red blood cells, macrophages and cell lines, and experimental organisms including rodents, rabbits and Zebrafish, offering some guidelines for development of safe GO-based nanocarriers. We conclude the paper by outlining the challenges involving GO-based formulations and future perspectives of this research in the biomedical field.
Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.