Potential Drug Delivery System Research Articles

Liposome as a Potential Drug Delivery System in Addressing Skin Diseases: A Review

Abstract: It was asserted that the manufacturing of liposomes, which was first disclosed in 1961, was a useful technology for drug encapsulation. Furthermore, there are several cosmetic items on the market now that include liposomes. The liposomes are novel drug carrier systems due to their similarity in lipid composition with the epidermal membrane. As a result, they penetrate the epidermis to a greater extent, showing enhanced skin absorption and increased effectiveness of the encapsulated drug molecule. This review briefly addresses the skin's anatomy, skin conditions, and the topical delivery of drugs for the treatment of skin diseases with emphasis on psoriasis by utilizing liposomes and other vesicular drug delivery systems along with challenges and opportunities in the treatment of skin diseases. When compared to alternative distribution methods, their resemblance to biological membranes enables entry into the epidermal barrier. Liposomes are good at penetrating the skin more deeply and reducing therapeutic side effects, which offers hope for the successful treatment of skin problems. Applying liposomes topically has several benefits, including better skin bioavailability and targeting, increased skin hydration by surface adhesiveness, protection of skin structure from external stress, and prolonged dermal release. Further, they have got potential to target the encapsulated drug molecule into pilosebaceous structure, making them an ideal candidate for the treatment of hair follicles and sebaceous gland disorder.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

Low fouling and pH-responsive poly(N-vinyl imidazole)/poly(ethylene glycol) methacrylate copolymer gels for colon targeted diclofenac sodium delivery

Protein and cell adhesion onto drug delivery matrices interferes with the predesigned drug delivery profile to the targeted site. Antifouling surfaces are needed to overcome this problem and improve the effectiveness and efficiency of drug delivery systems. Copolymers of N-vinyl imidazole (NVI) with poly(ethylene glycol methacrylate) (PEGMA) were synthesized via free radical polymerization under cryogenic conditions as potential pH-responsive drug delivery systems resistant to protein and cell adhesion. FTIR spectroscopy, elemental analysis, thermal analysis (DSC), mechanical tests, contact angle, surface energy, and SEM analysis provide the physicochemical properties of the samples. Static adsorption/adhesion experiments show that the copolymer cryogels resist BSA adhesion. Furthermore, the copolymer cryogels demonstrate anti-cell adhesion behavior against colon colorectal carcinoma (HCT-116) cells. They are non-cytotoxic toward HDFa fibroblasts. Diclofenac sodium (DS) - loaded copolymer cryogels show pH-dependent sustained drug delivery. The release studies show a limited release in stomach pH (2.0). On the other hand, enhanced release is observed in pH 5.0 and pH 7.4 within 15 h. The quantities of diclofenac sodium released from the copolymer cryogels are sufficient to show anti-inflammatory activity.

Injectable Hydrogels for Nervous Tissue Repair-A Brief Review.

The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications.

Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease

Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.

Tetracycline hydrochloride loaded-alginate based nanoparticle-hydrogel beads for potential wound healing applications: In vitro drug delivery, release kinetics, and antibacterial activity

Novel hydrogel beads based on nanocomposite with outstanding antibacterial and swelling capabilities have been successfully produced as an efficient drug carrier for potential drug delivery systems in wound healing applications. The beads were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and EDX-Mapping analysis. Then, using tetracycline hydrochloride (TCH) as a model drug system, they were studied in vitro for their potential efficiency as pH and temperature dependent sustained drug delivery carriers. Moreover, they were assessed in terms of porosity, swelling degree, encapsulation efficiency, and in vitro release kinetics. Beads released drugs at their highest levels under alkaline circumstances (pH = 8) and at a temperature of 39 °C, with a cumulative TCH release of 96.2 % at 36 h and in accordance with the Weibull kinetics model (R2 = 0.98). Additionally, the disc diffusion experiment demonstrated the strong antibacterial activity of the synthesized beads and offered a feasible and cost-effective wound dressing material for treating infected wounds.

Design of liposomal nanocarriers with a potential for combined dexamethasone and bevacizumab delivery to the eye

Clinicians face numerous challenges when delivering medications to the eyes topically because of physiological barriers, that can inhibit the complete dose from getting to the intended location. Due to their small size, the ability to deliver drugs of different polarities simultaneously, and their biocompatibility, liposomes hold great promise for ocular drug delivery. This study aimed to develop and characterise a dual loaded liposome formulation encapsulating Bevacizumab (BEV) and Dexamethasone (DEX) that possessed the physicochemical attributes suitable for topical ocular delivery. Liposomes were prepared by using thin film hydration followed by extrusion, and the formulations were optimised using a design of experiments approach. Physicochemical characterisation along with cytocompatibility and bioactivity of the formulations were assessed. Liposomes were successfully prepared with a particle size of 139 ± 2 nm, PDI 0.03 ± 0.01 and zeta potential −2 ± 0.7 mV for the optimised formulation. BEV and DEX were successfully encapsulated into the liposomes with an encapsulation efficiency of 97 ± 0.5 % and 26 ± 0.5 %, respectively. A sustained release of BEV was observed from the liposomes and the bioactivity of the formulation was confirmed using a wound healing assay. In summary, a potential topical eye drop drug delivery system, which can co-load DEX and BEV was developed and characterised for its potential to be used in ocular drug delivery.

Synthesis and supramolecular behavior study of a novel amphiphilic compound for idebenone encapsulation

The synthesis of a new amphiphilic compound obtained from galactose and glycerol monostearate is described, applying an efficient and environmentally friendly technique as is click reactions. The physicochemical characterization was carried out using nuclear magnetic resonance and high resolution mass spectrometry. Indeed, the novel compound enhances the solubility of idebenone, a hydrophobic active pharmaceutical ingredient. Transmission electron microscopy and molecular dynamics simulation were used to visualize the self-aggregated molecules, and dynamic light scattering to analyze the size of the supramolecular structure that shows nano-sized aggregates, with dimensions of up to 200 nm. The cytotoxicity and biocompatibility assay using murine macrophage RAW 264.7 cells showed no cytotoxicity at the 0.1 and 0.05 mg/ml concentration tested. Water solubility of idebenone increased sixteen-fold in the presence of the synthesized compound. Idebenone loading suggests that amphiphilic compound could be used as a potential drug delivery system in medicinal applications.

Liquisolids: A Modernistic approach in Drug Delivery System

Liquisolid Technology aims to make drug entities more soluble that have low solubility and low permeability, through the cosolvency theory in a reasonably simple setup that doesn't require expensive technology. A non-volatile solvent is used to dissolve a medicine into molecular dispersion, which is then converted into a powder that has the appearance of being dry and is easily compressible. Extrudates are produced from the material by extrusion using an extruder. To create spherical particles known as Pellets, the extrudates are placed beneath the spheronizer. These pellets or granules can be filled in capsules or can be compacted into tablets according to their dose and can be utilized. Various evaluation parameters like Carr`s Index, Angle of Repose, FTIR, etc was studied. Overall, the study demonstrated that the liqui-pellet might improve a liquisolid formulation's poor flowability, which is thought to be a significant development in the concept's commercial viability. The current review aims to unfurl the utilization of liquisolid technology as a potential drug delivery system for BCS class 2 and 3 drugs.

Enhancing apoptosis-mediated anticancer activity of evodiamine through protein-based nanoparticles in breast cancer cells

In the cutting-edge era of developing precision therapeutics, nanoparticles have emerged as a potent drug delivery system. Altering the size of poorly water-soluble drugs to nanoscale could confer change in their physical properties, including enhanced water solubility and bioavailability. Evodiamine (EVO), a natural indolequinone alkaloid extract from Evodia rutaecarpa, has shown several important pharmacological applications, anti-cancer being one of them. Protein-based nano-drug delivery systems have gained the interest of researchers due to their better biocompatibility, biodegradability, non-immunogenicity and non-toxicity. In the present study, EVO encapsulated BSA nanoparticles (ENPs) were synthesized and characterized, which were nanoscale-sized (~ 150 nm), monodispersed, spherical shaped, and showed high entrapment efficiency (~ 86%) and controlled drug release. The in-vitro anti-cancer activity of ENPs on human breast cancer cells was dose- and time-dependent. The apoptotic molecular mechanism investigated using FACS, qRT-PCR, and western blotting analysis, revealed increased expression of p53 and Bax and decreased expression of Bcl-2. Biological studies demonstrated comparatively more efficient and targeted delivery of ENPs than pure EVO. The comprehensive physiochemical characterization and in-vitro validation collectively pinpoint ENPs as a promising avenue for harnessing the therapeutic potential of the natural anti-cancer compound EVO. The findings indicate improved cytotoxicity, positioning ENPs as a propitious strategy for advancing breast cancer treatment.

Preliminary characterization of PEGylated nanostructured lipid carriers as potential drug delivery system

Preliminary characterization of PEGylated nanostructured lipid carriers as potential drug delivery system

A vivid outline demonstrating the benefits of exosome-mediated drug delivery in CNS-associated disease environments

The efficacy of drug delivery mechanisms has been improvised with time for different therapeutic purposes. In most cases, nano-sized delivery systems have been modeled over decades for the on-target applicability of the drugs. The use of synthetic drug delivery materials has been a common practice, although research has now focussed more on using natural vehicles, to avoid the side effects of synthetic delivery systems and easy acceptance by the body. Exosome is such a natural nano-sized vehicle that exceeds the efficiency of many natural vehicles, for being immune-friendly, due to its origin. Unlike, other natural drug delivery systems, exosomes are originated within the body's cells, and from there, they happen to travel through the extracellular matrices into neighboring cells. This capacity of exosomes has made them an efficient drug delivery system over recent years and now a large number of researches have been carried out to develop exosomes as natural drug delivery vehicles. Several experimental strategies have been practiced in this regard which have shown that exosomes are exclusively capable of carrying drugs and they can also be used in targeted delivery, for which they efficiently can reach and release the drug at their target cells for consecutive effects. One of the most interesting features of exosomes is they can cross the blood-brain barrier (BBB) in the body and hence, for the disease where other delivery vehicles are incapable of reaching the destination of the drug, exosomes can overcome the hurdle. This review particularly, focuses on the different aspects of using exosomes as a potential nano-sized drug delivery system for some of the severe diseases associated with the central nervous system of the human body.

Effective Strategies in Designing Chitosan-hyaluronic Acid Nanocarriers: From Synthesis to Drug Delivery Towards Chemotherapy.

The biomedical field faces an ongoing challenge in developing more effective anti-cancer medication due to the significant burden that cancer poses on human health. Extensive research has been conducted on the utilization of natural polysaccharides in nanomedicine owing to their properties of biocompatibility, biodegradability, non-immunogenicity, and non-toxicity. These characteristics make them a potent drug delivery system for cancer therapy. The chitosan hyaluronic acid nanoparticle (CSHANp) system, consisting of chitosan and hyaluronic acid nanoparticles, has exhibited considerable potential as a nanocarrier for various cancer drugs, rendering it one of the most auspicious systems presently accessible. The CSHANps demonstrate remarkable drug loading capacity, precise control over drug release, and exceptional selectivity towards cancer cells. These properties enhance the therapeutic effectiveness against cancerous cells. This article aims to provide a comprehensive analysis of CSHANp, focusing on its characteristics, production techniques, applications, and future prospects.

Human serum albumin as a potential drug delivery system for N-methylated hot spot insulin analogs inhibiting hormone aggregation

The purpose of this study was to investigate whether Human Serum Albumin (HSA) can bind N-methylated analogs of hot spots of native insulin. Three N-methylated derivatives of the A13–A19 fragment of native insulin were used: L(N-Me)YQLENY (1), LYQ(N-Me)LENY (2), and L(N-Me)YQ(N-Me)LENY (3). The studied N-methylated insulin fragments possess inhibiting potential against hormone aggregation. A variety of research techniques, including spectroscopic methods and microscopy assays, were used to study the interaction of HSA with the N-methylated insulin fragments. Based on spectroscopic measurements with Congo Red and Thioflavin T, all the analyzed N-methylated peptides were able to interact with the HSA surface. The CD spectrum registered for HSA in the presence of L(N-Me)YQLENY showed the smallest content of α-helix conformation, indicating the most compact HSA structure. Based on the results of MST, the dissociation constants (Kd) for complexes of HSA and peptides 1–3 were 19.2 nM (complex 1), 15.6 nM (complex 2), and 8.07 nM (complex 3). Microscopy assays, dynamic light scattering measurements as well as computer simulation of protein–ligand interaction also confirmed the possibility of docking the N-methylated inhibitors within HSA.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Unraveling the complex roles of macrophages in obese adipose tissue: an overview.

Macrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, and promoting mitochondrial transfer. Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions. Recently, the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology. In this review, we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity, as well as explore the potential of drug delivery systems targeting macrophages, aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.

The ameliorative role of Aloe vera-loaded chitosan nanoparticles on Staphylococcus aureus induced acute lung injury: Targeting TLR/NF-κB signaling pathways.

Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. These NPs can serve as potential candidates for the development of alternative antimicrobial agents.

Pillar[5]arene/albumin biosupramolecular systems for simultaneous native protein preservation and encapsulation of a water-soluble substrate.

The growing resistance of pathogens, bacteria, viruses, and fungi to a number of drugs has encouraged researchers to use natural and synthetic biomimetic systems to overcome this challenge. Multicomponent systems are an attractive approach for drug design and multitarget therapy. In this study, we report the assembly of a three-component (pillar[5]arene, bovine serum albumin, and methyl orange) biosupramolecular system as a potential drug delivery system. We estimated the cytotoxic activity and transfection ability of pillar[5]arene derivatives and investigated the effect of the nature of macrocycle functions (L-phenylalanine, glycine, L-alanine) on the native conformation of serum albumin in a three-component system. NMR, UV-vis, fluorescence, CD spectroscopy, DLS, and molecular docking studies were performed in order to confirm the structure and possible pillar[5]arene/bovine serum albumin/methyl orange interactions occurring during the association process. Results indicate that pillar[5]arene with L-phenylalanine fragments retains the native form of BSA to the maximum extent and forms more stable associates.

A smart thermoresponsive macroporous 4D structure by 4D printing of Pickering-high internal phase emulsions stabilized by plasma-functionalized starch nanomaterials for a possible delivery system

Hierarchically porous structures combine microporosity, mesoporosity, and microporosity to enhance pore accessibility and transport, which are crucial to develop high performance materials for biofabrication, food, and pharmaceutical applications. This work aimed to develop a 4D-printed smart hierarchical macroporous structure through 3D printing of Pickering-type high internal phase emulsions (Pickering-HIPEs). The key was the utilization of surface-active (hydroxybutylated) starch nanomaterials, including starch nanocrystals (SNCs) (from waxy maize starch through acid hydrolysis) or starch nanoparticles (SNPs) (obtained through an ultrasound treatment). An innovative procedure to fabricate the functionalized starch nanomaterials was accomplished by grafting 1,2-butene oxide using a cold plasma technique to enhance their surface hydrophobicity, improving their aggregation, and thus attaining a colloidally stabilized Pickering-HIPEs with a low concentration of each surface-active starch nanomaterial. A flocculation of droplets in Pickering-HIPEs was developed after the addition of modified SNCs or SNPs, leading to the formation of a gel-like structure. The 3D printing of these Pickering-HIPEs developed a highly interconnected large pore structure, possessing a self-assembly property with thermoresponsive behavior. As a potential drug delivery system, this thermoresponsive macroporous 3D structure offered a lower critical solution temperature (LCST)-type phase transition at body temperature, which can be used in the field of smart releasing of bioactive compounds.

Small molecule-based core and shell cross-linked nanoassemblies: from self-assembly and programmed disassembly to biological applications.

Supramolecular assemblies of stimuli-responsive amphiphilic molecules have been of utmost interest in targeted drug delivery applications, owing to their capability of sequestering drug molecules in one set of conditions and releasing them in another. To minimize undesired disassembly and stabilize noncovalently encapsulated drug molecules, the strategy of core or shell cross-linking has become a fascinating approach to constructing cross-linked polymeric or small molecule-based nanoassemblies. In this article, we discuss the design and synthetic strategies for cross-linked nanoassemblies from small molecule-based amphiphiles, with robust stability and enhanced drug encapsulation capability. We highlight their potential biomedical applications, particularly in drug or gene delivery, and cell imaging. This feature article offers a comprehensive overview of the recent developments in the application of small molecule-based covalently cross-linked nanocarriers for materials and biomedical applications, which may inspire the use of these materials as a potential drug delivery system for future chemotherapeutic applications.