Recent advances of electrospray technique for multiparticulate preparation: Drug delivery applications.

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.

Phytofabrication and Characterisation of Zinc Oxide Nanoparticles Using Pure Curcumin.

Zinc oxide and curcumin, on their own and in combination, have the potential as alternatives to conventional anticancer drugs. In this work, zinc oxide nanoparticles (ZnO NPs) were prepared by an eco-friendly method using pure curcumin, and their physicochemical properties were characterised. ATR-FTIR spectra confirmed the role of curcumin in synthesising zinc oxide curcumin nanoparticles (Green-ZnO-NPs). These nanoparticles exhibited a hexagonal wurtzite structure with a size and zeta potential of 27.61 ± 5.18 nm and -16.90 ± 0.26 mV, respectively. Green-ZnO-NPs showed good activity towards studied bacterial strains, including Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. The minimum inhibitory concentration of Green-ZnO-NPs was consistently larger than that of chemically synthesised ZnO NPs (Std-ZnO-NPs) or mere curcumin, advocating an additive effect between the zinc oxide and curcumin. Green-ZnO-NPs demonstrated an efficient inhibitory effect towards MCF-7 cells with IC50 (20.53 ± 5.12 µg/mL) that was significantly lower compared to that of Std-ZnO-NPs (27.08 ± 0.91 µg/mL) after 48 h of treatment. When Green-ZnO-NPs were tested against Artemia larvae, a minimised cytotoxic effect was observed, with LC50 being almost three times lower compared to that of Std-ZnO-NPs (11.96 ± 1.89 µg/mL and 34.60 ± 9.45 µg/mL, respectively). This demonstrates that Green-ZnO-NPs can be a potent, additively enhanced combination delivery/therapeutic agent with the potential for anticancer therapy.

Optimization of Chitosan-Decorated Solid Lipid Nanoparticles for Improved Flurbiprofen Transdermal Delivery.

Transdermal delivery is a potential alternative route to oral administration for drugs associated with stomach discomfort, such as flurbiprofen, a widely nonsteroidal anti-inflammatory drug (NSAID). This study aimed to design solid lipid nanoparticle (SLN) transdermal formulations of flurbiprofen. Chitosan-coated SLNs were prepared by the solvent emulsification method, and their properties and permeation profiles across the excised rat skin were characterized. The particle size of uncoated SLNs was at 695 ± 4.65 nm, which increased to 714 ± 6.13, 847 ± 5.38, and 900 ± 8.65 nm upon coating with 0.05, 0.10, and 0.20% of chitosan, respectively. The drug association efficiency was improved when a higher concentration of chitosan was employed over SLN droplets that endowed a higher affinity of flurbiprofen with chitosan. The drug release was significantly retarded as compared to the uncoated entities and followed non-Fickian anomalous diffusion that was depicted by "n" values of >0.5 and <1. Also, the total permeation of chitosan-coated SLNs (F7-F9) was significantly higher than that of the noncoated formulation (F5). Overall, this study has successfully designed a suitable carrier system of chitosan-coated SLNs that provide insight into the current conventional therapeutic approaches and suggest new directions for the advancements in transdermal drug delivery systems for improved permeation of flurbiprofen.

A Review on Physicochemical Properties of Polymers Used as Filaments in 3D-Printed Tablets.

Three-dimensional (3D) printing technology has presently been explored widely in the field of pharmaceutical research to produce various conventional as well as novel dosage forms such as tablets, capsules, oral films, pellets, subcutaneous implants, scaffolds, and vaginal rings. The use of this innovative method is a good choice for its advanced technologies and the ability to make tailored medicine specifically for individual patient. There are many 3D printing systems that are used to print tablets, implants, and vaginal rings. Among the available systems, the fused deposition modeling (FDM) is widely utilized. The FDM has been regarded as the best choice of printer as it shows high potential in the production of tablets as a unit dose in 3D printing medicine manufacturing. In order to design a 3D-printed tablet or other dosage forms, the physicochemical properties of polymers play a vital role. One should have proper knowledge about the polymer's properties so that one can select appropriate polymers in order to design 3D-printed dosage form. This review highlighted the various physicochemical properties of polymers that are currently used as filaments in 3D printing. In this manuscript, the authors also discussed various systems that are currently adopted in the 3D printing.

Advanced Drug Delivery Systems for Renal Disorders.

Kidney disease management and treatment are currently causing a substantial global burden. The kidneys are the most important organs in the human urinary system, selectively filtering blood and metabolic waste into urine via the renal glomerulus. Based on charge and/or molecule size, the glomerular filtration apparatus acts as a barrier to therapeutic substances. Therefore, drug distribution to the kidneys is challenging, resulting in therapy failure in a variety of renal illnesses. Hence, different approaches to improve drug delivery across the glomerulus filtration barrier are being investigated. Nanotechnology in medicine has the potential to have a significant impact on human health, from illness prevention to diagnosis and treatment. Nanomaterials with various physicochemical properties, including size, charge, surface and shape, with unique biological attributes, such as low cytotoxicity, high cellular internalization and controllable biodistribution and pharmacokinetics, have demonstrated promising potential in renal therapy. Different types of nanosystems have been employed to deliver drugs to the kidneys. This review highlights the features of the nanomaterials, including the nanoparticles and corresponding hydrogels, in overcoming various barriers of drug delivery to the kidneys. The most common delivery sites and strategies of kidney-targeted drug delivery systems are also discussed.

Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization.

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment.

As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages. The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based nanocarrier towards CRC treatment.

Synthesis, Characterization and In Vitro Evaluation of Chitosan Nanoparticles Physically Admixed with Lactose Microspheres for Pulmonary Delivery of Montelukast.

This study aimed to synthesise montelukast-loaded polymeric nanoparticles via the ionic gelation method using chitosan as a natural polymer and tripolyphosphate as a crosslinking agent. Tween 80, hyaluronic acid and leucine were added to modify the physicochemical properties of nanoparticles, reduce the nanoparticles' uptake by alveolar macrophages and improve powder aerosolisation, respectively. The nanoparticles ranged from 220 nm to 383 nm with a polydispersity index of ≤0.50. The zeta potential of nanoparticles ranged from 11 mV to 22 mV, with a drug association efficiency of 46-86%. The simple chitosan nanoparticles (F2) were more spherical in comparison to other formulations (F4-F6), while the roughness of hyaluronic acid (F5) and leucine (F6) added formulations was significantly high er than F2 and Tween 80 added formulation (F4). The DSC and FTIR analysis depict that the physical and chemical properties of the drug were preserved. The release of the drugs from nanoparticles was more sustained in the case of F5 and F6 when compared to F2 and F4 due to the additional coating of hyaluronic acid and leucine. The nanoparticles were amorphous and cohesive and prone to exhalation due to their small size. Therefore, nanoparticles were admixed with lactose microspheres to reduce particle agglomeration and improve powder dispersion from a dry powder inhaler (DPI). The DPI formulations achieved a dispersed fraction of 75 to 90%, a mass median aerodynamic diameter (MMAD) of 1-2 µm and a fine particle fraction (FPF) of 28-83% when evaluated using the Anderson cascade impactor from Handihaler®. Overall, the montelukast-loaded nanoparticles physically admixed with lactose microspheres achieved optimum deposition in the deep lung for potential application in asthmatic patients.

Synthesis and Characterization of Chitosan-Decorated Nanoemulsion Gel of 5-Fluorouracil for Topical Delivery.

(1) Background: The present study aimed to prepare chitosan-coated nanoemulsion gel containing 5-fluorouracil for enhanced topical delivery. (2) Methods: To formulate the nanoemulsion gel, oleic acid was used as the oil phase and Carbopol 940 as a gelling agent. Chitosan was used as a coating agent to control the release of 5-FU. Drug−excipient compatibility was evaluated using ATR-FTIR. The prepared nanoemulsion formulations were characterized based on particle size distribution, zeta potential, % encapsulation efficiency and drug content. In vitro drug release, skin drug retention and ex vivo permeation profiles were performed across rat skin using a Franz diffusion cell. Skin irritation experiments were also conducted on rats to examine the irritation potential of the formulations. (3) Results: It was found that the drug and excipients were compatible and chitosan successfully coated 5-FU, as demonstrated by ATR-FTIR results. The introduction of chitosan increased the size and zeta potential of the nanoemulsion. The 5-FU release in vitro was significantly lowered in the case of chitosan-decorated nanoemulsion (5-FU-C-NE), whereas the permeation and skin drug retention were higher in the case of 5-FU-C-NE. The formulations were proven non-irritant to the skin of the rats. The optimized formulation of the nanoemulsion was introduced into 1% Carbopol 940 gel. Incorporating the nanoemulsion into the gel further reduced the drug release in vitro and ex vivo permeation, whereas the retention of the drug in the skin was significantly increased (ANOVA; p < 0.05). The increase in skin retention was due to the presence of chitosan and Carbopol 940. The in vitro and ex vivo results were also confirmed with in vivo studies. Incorporating nanoemulsion into gel has resulted in higher Tmax, longer half-life and greater skin drug retention. (4) Conclusion: The results suggest that chitosan-decorated nanoemulsion gel is safe and can potentially be used to promote 5-FU skin retention, which is ideal for skin diseases such as melanoma.

Formulation of Polymers-Based Methotrexate Patches and Investigation of the Effect of Various Penetration Enhancers: In Vitro, Ex Vivo and In Vivo Characterization.

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug-excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed Cmax ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, Tmax was 8 h to 10 h, and t1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis.

Polymeric Microparticles: Synthesis, Characterization and In Vitro Evaluation for Pulmonary Delivery of Rifampicin.

Rifampicin, a potent broad-spectrum antibiotic, remains the backbone of anti-tubercular therapy. However, it can cause severe hepatotoxicity when given orally. To overcome the limitations of the current oral therapy, this study designed inhalable spray-dried, rifampicin-loaded microparticles using aloe vera powder as an immune modulator, with varying concentrations of alginate and L-leucine. The microparticles were assessed for their physicochemical properties, in vitro drug release and aerodynamic behavior. The spray-dried powders were 2 to 4 µm in size with a percentage yield of 45 to 65%. The particles were nearly spherical with the tendency of agglomeration as depicted from Carr's index (37 to 65) and Hausner's ratios (>1.50). The drug content ranged from 0.24 to 0.39 mg/mg, with an association efficiency of 39.28 to 96.15%. The dissolution data depicts that the in vitro release of rifampicin from microparticles was significantly retarded with a higher L-leucine concentration in comparison to those formulations containing a higher sodium alginate concentration due to its hydrophobic nature. The aerodynamic data depicts that 60 to 70% of the aerosol mass was emitted from an inhaler with MMAD values of 1.44 to 1.60 µm and FPF of 43.22 to 55.70%. The higher FPF values with retarded in vitro release could allow sufficient time for the phagocytosis of synthesized microparticles by alveolar macrophages, thereby leading to the eradication of M. tuberculosis from these cells.

Vibrio spp. and Their Vibriocin as a Vibriosis Control Measure in Aquaculture.

Vibriosis disease is a major threat to the aquaculture industry caused by Vibrio spp. that are often resistant to antibiotics. Alternative controlling measures such as bacteriocins could be effective due to their narrow-spectrum activity. Hence, this systematic literature review (SLR) was carried out to review the feasibility of Vibrio spp. and their vibriocins to be used as a vibriosis control measure in aquaculture. A literature search using the web of science (WOS) and SCOPUS databases resulted in 42 unique articles which were reviewed. The results showed that Vibrio spp. could be used as a probiotic to control vibriosis, but not recommended due to their opportunistic nature and pathogenesis. Vibriocin showed narrow-spectrum activity against Vibrio spp. including highly pathogenic strains such as V. alginolyticus, V. harveyi, and V. parahaemolyticus. This supported this review's hypothesis of using vibriocin as a targeted vibriosis control measure. Vibrio cholerae was the most studied and showed the highest inhibition range, inhibiting 13 different vibrio and non-vibrio species. Various innovations were reported in the field and vibriocins can now be produced on large scales using whole-cell culture. Vibriocins were structurally diverse, large molecular weight, and relatively heat stable. These vibriocins mainly inhibited the cell wall but could have other novel mechanisms. These properties could affect the extraction process as well as applications in aquaculture, hence, should be considered in future research.

Chitosan oleate-tripolyphosphate complex-coated calcium alginate bead: Physicochemical aspects of concurrent core-coat formation.

This study designed chitosan species-coated calcium alginate beads through concurrent core-coat formation. Chitosan oleate was synthesized by carbodiimide chemistry and characterized by 1H NMR and FTIR techniques. Chitosan or chitosan oleate was coated onto the forming alginate or alginate/tripolyphosphate core using vibratory nozzle extrusion-microencapsulation approach, followed by calcium crosslinking. Chlorpheniramine maleate served as a model water-soluble drug. The molecular characteristics, size, shape, morphology, swelling, erosion, water uptake, drug content and drug release profiles of beads were evaluated. Discrete spherical coated beads were obtained through minimizing successive bead adhesion through an interplay of nozzle vibrational frequency and polymeric solution flow rate. The tripolyphosphate ions in the core possessed higher diffusional kinetics than alginate and were better able to attract chitosan species onto bead surfaces to facilitate alginate-chitosan coacervation. Amphiphilic chitosan oleate formed smaller aggregates than chitosan. It interacted with greater ease with core alginate and tripolyphosphate. The gain in alginate/tripolyphosphate interaction with chitosan oleate at the core-coat interface enhanced bead robustness against swelling and water uptake with drug release consequently dependent on the loss of alginate-drug interaction.

Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery.

Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.

Alginate Nanoformulation: Influence of Process and Selected Variables.

Nanocarriers are defined as structures and devices that are constructed using nanomaterials which add functionality to the encapsulants. Being small in size and having a customized surface, improved solubility and multi-functionality, it is envisaged that nanoparticles will continue to create new biomedical applications owing to their stability, solubility, and bioavailability, as well as controlled release of drugs. The type and physiochemical as well as morphological attributes of nanoparticles influence their interaction with living cells and determine the route of administration, clearance, as well as related toxic effects. Over the past decades, biodegradable polymers such as polysaccharides have drowned a great deal of attention in pharmaceutical industry with respect to designing of drug delivery systems. On this note, biodegradable polymeric nanocarrier is deemed to control the release of the drug, stabilize labile molecules from degradation and site-specific drug targeting, with the main aim of reducing the dosing frequency and prolonging the therapeutic outcomes. Thus, it is essential to select the appropriate biopolymer material, e.g., sodium alginate to formulate nanoparticles for controlled drug delivery. Alginate has attracted considerable interest in pharmaceutical and biomedical applications as a matrix material of nanocarriers due to its inherent biological properties, including good biocompatibility and biodegradability. Various techniques have been adopted to synthesize alginate nanoparticles in order to introduce more rational, coherent, efficient and cost-effective properties. This review highlights the most used and recent manufacturing techniques of alginate-based nanoparticulate delivery system, including emulsification/gelation complexation, layer-by-layer, spray drying, electrospray and electrospinning methods. Besides, the effects of the main processing and formulation parameters on alginate nanoparticles are also summarized.

Alginate-C18 Conjugate Nanoparticles Loaded in Tripolyphosphate-Cross-Linked Chitosan-Oleic Acid Conjugate-Coated Calcium Alginate Beads as Oral Insulin Carrier.

Simple alginate, alginate-stearic acid, and alginate-C18 conjugate nanoparticles and tripolyphosphate-cross-linked chitosan-oleic acid conjugate-coated calcium alginate beads as the vehicle of nanoparticles were designed. Their size, ζ potential, morphology, drug load, drug release, matrix molecular characteristics, mucus penetration, HT-29 cell line cytotoxicity and intracellular trafficking, in vivo blood glucose lowering, and insulin delivery profiles were characterized. Alginate-C18 conjugate nanoparticles were nontoxic. Among all nanoparticle variants, they had reduced size and ζ potential thus enhancing particulate mucus penetration and intracellular trafficking. Their insulin reabsorption tendency was minimized as alginate active COOH/COO- sites were preoccupied with C18. Their loading into coated beads was translated to reduced drug release in simulated gastric phase with nanoparticles being released in the intestinal phase. The combination dosage form increased the blood glucose lowering extent of insulin and blood insulin level compared with nanoparticles or beads alone. Nanoparticles in beads represented a viable approach for oral insulin delivery.