Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2 months at 40 ± 2 °C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.
This study investigates the impact of various chain lengths of hydrophilic polyglycerol fatty acid esters (HPGEs), namely SWA-10D, M-7D and M-10D on protein interactions and their influence on the surface morphology and interfacial properties of low-fat aerated emulsions under different pressures conditions. M-7D and M-10D samples exhibited larger particle sizes, higher ζ-potential and rougher surface compared to SWA-10D sample at 1 % concentration of HPGEs. Consequently, M-7D and M-10D samples demonstrated lower values of G', G'', and higher values tan δ at the oil-water interface as pressure increased, thereby promoting the formation of less viscoelastic structures. M-7D sample, characterized by lower content of α-helix structures, resulted in an observable redshift in the NH and CO groups of the protein. Molecular docking analysis affirmed that M-7D sample exhibited a lower absolute binding energy value, indicating stronger interaction with the protein compared to other samples, ultimately contributing to the unstable interfacial membrane formed.
The electrospray (ES) technique has proven to be an effective and a versatile approach for crafting drug delivery carriers with diverse dimensions, multiple layers, and varying morphologies. Achieving the desired particle properties necessitates careful optimization of various experimental parameters. This review delves into the most prevalent ES system configurations employed for this purpose, such as monoaxial, coaxial, triaxial, and multi-needle setups with solid or liquid collector. In addition, this work underscores the significance of ES in drug delivery carriers and its remarkable ability to encapsulate a wide spectrum of therapeutic agents, including drugs, nucleic acids, proteins, genes and cells. Depth examination of the critical parameters governing the ES process, including the choice of polymer, surface tension, voltage settings, needle size, flow rate, collector types, and the collector distance was conducted with highlighting on their implications on particle characteristics, encompassing morphology, size distribution, and drug encapsulation efficiency. These insights illuminate ES's adaptability in customizing drug delivery systems. To conclude, this review discusses ES process optimization strategies, advantages, limitations and future directions, providing valuable guidance for researchers and practitioners navigating the dynamic landscape of modern drug delivery systems.
Nanoparticles as cancer therapeutic carrier fail in clinical translation due to complex biological environments in vivo consisting of electrolytes and proteins which render nanoparticle aggregation and unable to reach action site. This review identifies the desirable characteristics of nanoparticles and their constituent materials that prevent aggregation from site of administration (oral, lung, injection) to target site. Oral nanoparticles should ideally be 75-100 nm whereas the size of pulmonary nanoparticles minimally affects their aggregation. Nanoparticles generally should carry excess negative surface charges particularly in fasting state and exert steric hindrance through surface decoration with citrate, anionic surfactants and large polymeric chains (polyethylene glycol and polyvinylpyrrolidone) to prevent aggregation. Anionic as well as cationic nanoparticles are both predisposed to protein corona formation as a function of biological protein isoelectric points. Their nanoparticulate surface composition as such should confer hydrophilicity or steric hindrance to evade protein corona formation or its formation should translate into steric hindrance or surface negative charges to prevent further aggregation. Unexpectedly, smaller and cationic nanoparticles are less prone to aggregation at cancer cell interface favoring endocytosis whereas aggregation is essential to enable nanoparticles retention and subsequent cancer cell uptake in tumor microenvironment. Present studies are largely conducted in vitro with simplified simulated biological media. Future aggregation assessment of nanoparticles in biological fluids that mimic that of patients is imperative to address conflicting materials and designs required as a function of body sites in order to realize the future clinical benefits.
The potential of ultrasonication-driven molecular self-assembly of whey protein isolate (WPI) with chitosan (CS)/chitooligosaccharide (COS) to stabilize Pickering emulsions was examined, based on CS/COS ligands-induced partial unfolding in remodeling the Pickering particles features. Multi-spectral analysis suggested obvious changes in conformational structures of WPI due to interaction with CS/COS, with significantly higher unfolding degrees of WPI induced by COS. Non-covalent interactions were identified as the major forces for WPI-CS/COS conjugates. Ultrasonication enhanced electrostatic interaction between CS's -NH3 groups and WPI's -COO- groups which improved emulsification activity and storability of WPI-COS stabilized Pickering emulsion. This was attributed to increased surface hydrophobicity and decreased particle size compared to WPI-CS associated with differential unfolding degrees induced by different saccharide ligands. CLSM and SEM consistently observed smaller emulsion droplets in WPI-COS complexes than WPI-CS/COS particles tightly adsorbed at the oil-water interface. The electrostatic self-assembly of WPI with CS/COS greatly enhanced the encapsulation efficiency of quercetin than those stabilized by WPI alone and ultrasound further improved encapsulation efficiency. This corresponded well with the quantitative affinity parameters between quercetin and WPI-CS/COS complexes. This investigation revealed the great potential of glycan ligands-induced conformational transitions of extrinsic physical disruption in tuning Pickering particle features.
Gastrointestinal diseases exert a profound impact on global health, leading to millions of healthcare interventions and a significant number of fatalities annually. This, coupled with escalating healthcare expenditures, underscores the need for identifying and addressing potential exacerbating factors. One emerging concern is the pervasive presence of microplastics and nano-plastics in the environment, largely attributed to the indiscriminate usage of disposable plastic items. These nano-plastics, having infiltrated our food chain, pose a potential threat to gastrointestinal health. To understand this better, we co-cultured human gastric fibroblasts (HGF) with polystyrene nano-plastics (PS-NPs) of diverse sizes (80, 500, 650 nm) and meticulously investigated their cellular responses over a 24-hour period. Our findings revealed PS particles were ingested by the cells, with a notable increase in ingestion as the particle size decreased. The cellular death induced by these PS particles, encompassing both apoptosis and necrosis, showcased a clear dependence on both the particle size and its concentration. Notably, the larger PS particles manifested more potent cytotoxic effects. Further analysis indicated a concerning reduction in cellular membrane potential, alongside a marked increase in ROS levels upon PS particles exposure. This suggests a significant disruption of mitochondrial function and heightened oxidative stress. The larger PS particles were especially detrimental in causing mitochondrial dysfunction. In-depth exploration into the PS particles impact on genes linked with the permeability transition pore (PTP) elucidated that these PS particles instigated an internal calcium rush. This surge led to a compromise in the mitochondrial membrane potential, which in tandem with raised ROS levels, further catalyzed DNA damage and initiated cell death pathways. In essence, this study unveils the intricate mechanisms underpinning cell death caused by PS particles in gastric epithelial cells and highlighting the implications of PS particles on gastrointestinal health. The revelations from this research bear significant potential to shape future healthcare strategies and inform pertinent environmental policies.
Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.
Chitosan (CS) based nanoparticles (NPs) were fabricated via an ionic gelation reaction modified by flaxseed gum (FG) or sodium tripolyphosphate (STPP). The average particle size, morphology, interfacial tension, and wettability of NPs were characterized. The particle size of CS-STPP-HA (hyaluronic acid)-FA (ferulic acid) NPs and CS-FG-HA-FA NPs was 400.8 nm and 262.4 nm, respectively under the optimized conditions of CS/STPP = 5:1 (w/w) or CS/FG = 1:1 (v/v) with HA concentration of 0.25 mg/mL and FA dosage of 25 μM. FG acted as a good alternative for STPP to form particles with CS in stabilizing Pickering emulsion with an internal diacylglycerol (DAG) phase of 50-80 % (v/v). The complex nanoparticles had high surface activity and contact angle close to 90 °C, being able to tightly packed at the droplet surface. The emulsions had high thermal, ionic and oxidative stability. With the aid of moisturizing polysaccharides and DAG oil, the emulsions had a good sustained-release ability for FA with deeper penetration and retention into the dermis of the skin. Thus, FG and HA-based NPs serve as green vehicles for the fabrication of novel Pickering emulsions and possess great potential to be applied as a delivery system for lipophilic active agents in functional food and cosmetic products.
Objective: The nasal cavity effectively captures the particles present in inhaled air, thereby preventing harmful and toxic pollutants from reaching the lungs. This filtering ability of the nasal cavity can be effectively utilized for targeted nasal drug delivery applications. This study aims to understand the particle deposition patterns in three age groups: neonate, infant, and adult.Materials and methods: The CT scans are built using MIMICS 21.0, followed by CATIA V6 to generate a patient-specific airway model. Fluid flow is simulated using ANSYS FLUENT 2021 R2. Spherical monodisperse microparticles ranging from 2 to 60 µm and a density of 1100 kg/m3 are simulated at steady-state and sedentary inspiration conditions.Results: The highest nasal valve depositions for the neonate are 25% for 20 µm, for infants, 10% for 50 µm, 15% for adults, and 15% for 15 µm. At mid nasal region, deposition of 15% for 20 µm is observed for infant and 8% for neonate and adult nasal cavities at a particle size of 10 and 20 µm, respectively. The highest particle deposition at the olfactory region is about 2.7% for the adult nasal cavity for 20 µm, and it is <1% for neonate and infant nasal cavities.Discussion and conclusions: The study of preferred nasal depositions during natural sedentary breathing conditions is utilized to determine the size that allows medication particles to be targeted to specific nose regions.
α-mangostin (AM) is a promising natural anticancer agent that can be used in cancer research. However, its effectiveness can be limited by poor solubility and bioavailability. To address this issue, chitosan-based nanoparticles (CSNPs) have been investigated as a potential delivery system to enhance the cytotoxicity to cancer cells and improve selectivity against normal cells. In this study, we developed folate-conjugated chitosan nanoparticles (F-CS-NPs) using a carbodiimide-based conjugation method to attach folate to chitosan (CS), which have different molecular weights. The NPs were crosslinked using tripolyphosphate (TPP) via ionic gelation. To characterize the F-CS-NPs, we utilized various analytical techniques, including transmission electron microscopy (TEM) to evaluate the particle size and morphology, Fourier-transform infrared spectroscopy (FTIR) to confirm the presence of functional groups, and ultraviolet-visible spectroscopy (UV-Vis) to measure the absorption spectrum and confirm the presence of folate. The particle size of AM-F-CS-NPs ranged from 180 nm to 250 nm, with many having favorable charges ranging from +40.33 ± 3.4 to 10.69 ± 1.3 mV. All NPs exhibited the same spherical morphology. The use of F-CS-NPs increased drug release, followed by a sustained release pattern. We evaluated the cytotoxicity of AM, AM-F-CS-HMW, and AM-F-CS-LMW NPs against MCF-7 cells and found IC50 values of 8.47 ± 0.49, 5.3 ± 0.01, and 4.70 ± 0.11 µg/mL, respectively. These results confirm the improved cytotoxicity of AM in MCF-7 cells when delivered via F-CS-NPs. Overall, our in vitro study demonstrated that the properties of F-CS-NPs greatly influence the cytotoxicity of AM in MCF-7 breast cancer cells (significantly different (p < 0.05)). The use of F-CS-NPs as a drug-delivery system for AM may have the potential to develop novel therapies for breast cancer.
Atopic dermatitis is one of the most widespread chronic inflammatory skin conditions that can occur at any age, though the prevalence is highest in children. The purpose of the current study was to prepare and optimize the azelaic acid (AzA) loaded SNEDDS using Pseudo ternary phase diagram, which was subsequently incorporated into the Carbopol 940 hydrogel for the treatment of atopic dermatitis. The composition was evaluated for size, entrapment efficiency, in vitro, ex vivo, and in vivo studies. The polydispersity index of the optimized preparation was found to be less than 0.5, and the size of the distributed globules was found to be 151.20 ± 3.67 nm. The SNEDDS hydrogel was characterized for pH, viscosity, spreadability, and texture analysis. When compared to the marketed formulation, SNEDDS hydrogel was found to have a higher rate of permeation through the rat skin. In addition, a skin irritation test carried out on experimental animals showed that the SNEDDS formulation did not exhibit any erythematous symptoms after a 24-h exposure. In conclusion, the topical delivery of AzA through the skin using SNEDDS hydrogel could prove to be an effective approach for the treatment of atopic dermatitis.
Probiotics viability and stability is a core challenge for the food processing industry. To prolong the viability of probiotics (Lactobacillus acidophilus), gelatin (GE)-chitosan (CH) polyelectrolytes-coated nanoliposomes were developed and characterized. The average particle size of the nanoliposomes was in the range of 131.7-431.6 nm. The mean zeta potential value of the nanoliposomes differed significantly from -42.2 to -9.1 mV. Scanning electron micrographs indicated that the nanoliposomes were well distributed and had a spherical shape with a smooth surface. The Fourier transform infrared spectra revealed that the GE-CH polyelectrolyte coating has been effectively applied on the surface of nanoliposomes and L. acidophilus cells were successfully encapsulated in the lipid-based nanocarriers. X-ray diffraction results indicated that nanoliposomes are semicrystalline and GE-CH polyelectrolyte coating had an influence on the crystalline nature of nanoliposomes. Moreover, the coating of L. acidophilus-loaded nanoliposomes with GE-CH polyelectrolytes significantly improved its viability when exposed to simulated gastrointestinal environments. The findings of the current study indicated that polyelectrolyte-coated nanoliposomes could be used as an effective carrier for the delivery of probiotics and their application to food matrix for manufacturing functional foods.
Core-shell biopolymer nanoparticles are assembled from a hydrophobic protein (zein) core and a hydrophilic polysaccharide (carboxymethyl dextrin) shell. The nanoparticles were shown to have good stability and the ability to protect quercetin from chemical degradation under long-term storage, pasteurization, and UV irradiation. Spectroscopy analysis shows that electrostatic, hydrogen bonding, and hydrophobic interactions are the main driving forces for the formation of composite nanoparticles. Quercetin coated with nanoparticles significantly enhanced its antioxidant and antibacterial activities and showed good stability and slow release in vitro during simulated gastrointestinal digestion. Furthermore, the encapsulation efficiency of carboxymethyl dextrin-coated zein nanoparticles (81.2%) for quercetin was significantly improved compared with that of zein nanoparticles alone (58.4%). These results indicate that carboxymethyl dextrin-coated zein nanoparticles can significantly improve the bioavailability of hydrophobic nutrient molecules such as quercetin and provide a valuable reference for their application in the field of biological delivery of energy drinks and food.
The purpose of this work was to establish the best particle size for recovering high yields of total phenolic compounds (TPC), total anthocyanin compounds(TAC) and total flavonoid compounds (TFC) from roselle (Hibiscus sabdariffa) by applying supercritical carbon dioxide (ScCO2). The extraction rate, diffusivity and solubility of yield in ScCO2 were also studied and calculated utilizing models. Pressure (10 and 30 MPa), temperature (40 and 60 °C), and particle size (250 µm size of 250 µm size of roselle provides the maximum bioactive compound recovery and solubility. Furthermore, the diffusivity and extraction of ScCO2 are increased by decreasing the particle size. Therefore, a smaller particle size is appropriate for roselle extraction by ScCO2 based on the experimental and modelling data.
Starch nanocrystals (SNCs) are tiny particles that possess unique qualities due to their small size, such as increased crystallinity, thin sheet structure, low permeability, and strong resistance to digestion. Although sago starch nanocrystals (SNCs) are naturally hydrophilic, their properties can be modified through chemical modifications to make them more versatile for various applications. In this study, the esterification process was used to modify SNCs using lauroyl chloride (LC) to enhance their surface properties. Three different ratios of LC to SNC were tested to determine the impact on the modified SNC (mSNC). The chemical changes in the mSNC were analyzed using FTIR and 1H NMR spectroscopy. ##The results showed that as the amount of LC increased, the degree of substitution (DS) also increased, which reduced the crystallinity of the mSNC and its thermal stability. However, the esterification process also improved the hydrophobicity of the SNC, making it more amphiphilic. The emulsification capabilities of the mSNC were investigated using a Pickering emulsion, and the results showed that the emulsion made from mSNC-1.0 had better stability than the one made from pristine SNC. This study highlights the potential of SNC as a particle emulsifier and demonstrates how esterification can improve its emulsification capabilities.
Disulfiram (DS) is an anti-alcoholism drug capable of acting against important and hard-to-treat cancers. The drug's relative instability and variable absorption/distribution have led to its variable pharmacokinetics and suboptimal exposure. Hence, it was hypothesised that a nano-enabled form of DS might be able to overcome such limitations. Encapsulation of the labile DS was achieved with quaternary ammonium palmitoyl glycol chitosan (GCPQ) to form a high-capacity, soybean oil-based DS-GCPQ nanoemulsion. DS-GCPQ showed capability of oil-loading up to 50% v/v for a stable entrapment of high drug content. With increasing oil content (10 to 50% v/v), the mean particle size and polydispersity index were also increased (166 to 351 nm and 0.14 to 0.22, respectively) for a given amount of GCPQ. Formulations showed a highly positive particle surface charge (50.9 ± 1.3 mV), contributing to the colloidal stability of the individual particles. DS-GCPQ showed marked cytotoxicity against pancreatic cancer cell lines with enhanced activity in the presence of copper. An intravenous pharmacokinetic study of DS-GCPQ in vivo showed improved plasma drug stability with a DS half-life of 17 min. Prolonged survival was seen in tumour-bearing animals treated with DS-GCPQ supplemented with copper. In conclusion, DS-GCPQ nanoemulsion has the potential to be developed further for cancer therapeutic purposes.
With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.
Chitosan is one of the valuable products obtained from crustacean waste. The unique characteristics of chitosan (antimicrobial, antioxidant, anticancer, and anti-inflammatory) have increased its application in various sectors. Besides unique biological properties, chitosan or chitosan-based compounds can stabilize emulsions. Nevertheless, studies have shown that chitosan cannot be used as an efficient stabilizer because of its high hydrophilicity. Hence, this review aims to provide an overview of recent studies dealing with improving the emulsifying properties of chitosan. In general, two different approaches have been reported to improve the emulsifying properties of chitosan. The first approach tries to improve the stabilization property of chitosan by modifying its structure. The second one uses compounds such as polysaccharides, proteins, surfactants, essential oils, and polyphenols with more wettability and emulsifying properties than chitosan's particles in combination with chitosan to create complex particles. The tendency to use chitosan-based particles to stabilize Pickering emulsions has recently increased. For this reason, more studies have been conducted in recent years to improve the stabilizing properties of chitosan-based particles, especially using the electrostatic interaction method. In the electrostatic interaction method, numerous research has been conducted on using proteins and polysaccharides to increase the stabilizing property of chitosan.
Surface roughness of carrier particles can impact dry powder inhaler (DPI) performance. There are opposing views on the effect of roughness on DPI performance. Hence, a systematic approach is needed to modify carrier surfaces and evaluate the impact on drug delivery. Carrier particle surfaces were modified by fluid bed coating with saturated lactose containing micronized lactose of different sizes (2, 5 and 8 μm) and coated to different levels (20, 40, 60 and 80%). Their drug delivery performance was assessed by the fine particle fraction (FPF). Roughness parameters, mean arithmetic roughness (Ra) and arithmetic mean height (Sa), of the carrier particles, were also evaluated using optical profilometry and scanning laser microscopy. Generally, particles of higher Ra had higher FPF. Higher Sa resulted in higher FPF only for particles with 60 and 80% coat levels. Reduced contact surface area between the drug particle and rougher carrier particle resulted in easier drug detachment during aerosolization. The 5 µm micronized lactose produced optimal carrier particles with respect to FPF and surface roughness. The study highlighted that with the ideal particles for surface roughening and coating level, surface roughening could be efficiently achieved by fluid bed coating for superior DPI performance.
Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.