Applications In Drug Delivery Systems Research Articles

Chitosan/Graphene Oxide Composite Films and Their Biomedical and Drug Delivery Applications: A Review

The healing of wounds is still a challenging clinical problem for which an efficient and fast treatment is needed. Therefore, recent studies have created a new generation of wound dressings that can accelerate the wound healing process with minimal side effects. Chitosan, a natural biopolymer, is an attractive candidate for preparing biocompatible dressings. The biodegradability, non-toxicity, and antibacterial activities of chitosan have made it a promising biopolymer for treating wounds. Graphene oxide has also been considered by researchers as a non-toxic, inexpensive, and biocompatible material for wound healing applications. This review paper discusses the potential use of chitosan/graphene oxide composite films and their application in wound dressing and drug delivery systems.

Supramolecular Gels Incorporating Cordyline terminalis Leaf Extract as a Polyphenol Release Scaffold for Biomedical Applications.

Cordyline terminalis leaf extract (aqCT) possesses abundant polyphenols and other bioactive compounds, which are encapsulated in gelatin–polyethylene glycol–tyramine (GPT)/alpha-cyclodextrin (α-CD) gels to form the additional functional materials for biomedical applications. In this study, the gel compositions are optimized, and the GPT/α-CD ratios equal to or less than one half for solidification are found. The gelation time varies from 40.7 min to 5.0 h depending on the increase in GPT/α-CD ratios and aqCT amount. The aqCT extract disturbs the hydrogen bonding and host–guest inclusion of GPT/α-CD gel networks, postponing the gelation. Scanning electron microscope observation shows that all gels with or without aqCT possess a microarchitecture and porosity. GPT/α-CD/aqCT gels could release polyphenols from 110 to 350 nmol/mL at the first hour and sustainably from 5.5 to 20.2 nmol/mL for the following hours, which is controlled by feeding the aqCT amount and gel properties. GPT/α-CD/aqCT gels achieved significant antioxidant activity through a 100% scavenging DPPH radical. In addition, all gels are non-cytotoxic with a cell viability more than 85%. Especially, the GPT3.75α-CD10.5aqCT gels with aqCT amount of 3.1–12.5 mg/mL immensely enhanced the cell proliferation of GPT3.75α-CD10.5 gel without extract. These results suggest that the inherent bioactivities of aqCT endowed the resulting GPT/α-CD/aqCT gels with effective antioxidant and high biocompatibility, and natural polyphenols sustainably release a unique platform for a drug delivery system or other biomedical applications.

Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering

AbstractDifferently to most chemically synthesized medical materials, polyhydroxyalkanoates (PHAs) are intracellular carbon and energy storage granules, which is a family of natural bio‐polymers synthesized by microorganism's materials. Due to excellent biocompatibility reasonable biodegradability and versatile material difference, PHAs are well medical biomaterials candidates for applications in tissue engineering and drug delivery, including commercial PHB, PHBV, PHBHHx, PHBVHHx, P34HB and few uncommercial PHAs. Electrospinning nanofibers with the size of 10–10,000 nm can improve the mechanical properties and decrease the crystallinity of PHA, meanwhile simulate the structure and function of native extracellular matrix of cells. Hence, PHAs electrospinning nanofibers as engineered scaffolds have been widely used for tissue engineering scaffolds in cardiovascular, vascular, nerve, bone, cartilage and skin; also, as carriers for application in drug delivery system. In this review, we highlight the extraction and properties of medical PHAs from natural or engineered microorganism, and microstructure, current manufacturing techniques and medical applications of electrospinning nanofibers of PHAs. Moreover, the current challenges and prospects of PHAs electrospinning nanofibers are discussed rationally, providing an insight into developing vibrant fields of PHAs electrospinning nanofibers‐based biomedicine.

Simple fabrication of biocompatible chitosan/graphene oxide microspheres for pH-controlled amoxicillin delivery

Chitosan (CS) is one of the main members of the polysaccharide family which could be used for obtaining a system with a pH-controlled and sustained drug release profile. By considering this, the current research describes the simple fabrication of a series of the new pH-sensitive microspheres based on CS and graphene oxide (GO) to evaluate their efficiency as the drug carrier. The successful formation of the CS/GO microspheres was explored via several characterization techniques. Amoxicillin (AMX) as an antibacterial drug was loaded about 78%-89% in the prepared microspheres (AMX@CS/GO). The highest drug loading value was obtained for CS/GO; 15%. Drug release and MTT tests respectively approved the positive influence of CS in obtaining sustained and pH-controlled AMX release behavior and more biocompatibility. From this isotherm study, the maximum binding capacity of CS/GO 15% for AMX was determined at about 172.41 mg g−1. The antibacterial activity of the AMX loaded microspheres was confirmed via the disc diffusion method. In conclusion, the outputs of this work revealed that the fabricated CS/GO 15% could be potentially proposed as a biocompatible system for drug delivery applications.

Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases.

The increasing burden of respiratory diseases caused by microbial infections poses animmense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.

A Comparative Study on Applications of Novel Drug Delivery System for Herbal Formulations

For plant actives and extracts, novel drug delivery systems (NDDS) have made great strides in the past few years. Bioactive and plant extracts have been used to create a variety of novel herbal formulations, including polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microspheres, transferosomes, and ethosomes. There are a number of advantages that the novel formulations have over conventional formulations, including improved solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, improved tissue distribution of macrophages, sustained delivery, and protection from physical or chemical degradation, among others. A review of the current state of herbal formulation development, including preparation method, active ingredient type, size, entrapment efficiency, route of administration and biological activity is highlighted in the present work.

Construction of N-Doped Hollow Carbon Nanospheres Through a Novel Self-Template Strategy as High-Performance Electrode Materials for Supercapacitors

N-doped hollow carbon nanospheres (NHCSs) with mesopores-rich hierarchical structure have been synthesized by a self-template strategy using resorcinol-formaldehyde resin as precursors. The crucial point of this strategy is the selective dissolution of acetones for oligomers and subsequent rearrangement dependent on the structure-directing agent (CTAB). The large specific surface area (1325.0 m2 g−1), abundant and accessible mesopores (6.6 nm), unexpected nitrogen doping concentration (3.5 wt.%), and favorable graphitization (0.88), enable the as-prepared NHCSs to be a candidate for energy storage materials. When utilized as supercapacitor electrode, the NHCSs exhibit high specific capacitance of 293.1 F g−1 at 0.5 A g−1, impressive rate performance of 225.0 F g−1 at 20 A g−1, and good cycling performance (over 88.24% the peak capacity was retained after 5000 cycles at 5 A g−1). The self-template strategy displays potential prospects as a versatile route to reconstruct porous structures of carbon materials from phenolic resin polymers, thereby broadening the applications in drug delivery, adsorption, and energy storage systems.

Loading and release of\xa0cancer chemotherapy drugs utilizing simultaneous temperature and pH-responsive nanohybrid

BackgroundRecently, the development of nanocarriers and the improvement of their biochemical properties have became of great importance. Single-walled carbon nanotubes (SWCNT) have many applications in drug delivery systems (DDS) as a common carbon-based structure. In the current work, the penetration, co-loading, and co-release of Doxorubicin (DOX) and Paclitaxel (PAX), as two cancer chemotherapy agents, were investigated using a novel modified copolymer with functionalized SWCNT.ResultsThis study proposes a dual-responsive smart carrier that is sensitive to pH and temperature. The carrier consists of functionalized SWNT and Dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) grafting on SWCNT. This suggested carrier was investigated by utilizing molecular simulations. Interaction energies between DOX, PAX, and carrier as well as the affinity of drugs to the nanocarrier were studied. The energy analysis of drug release and adsorption presented that DOX and PAX delivery using this carrier is selective and sensitive at healthy and cancerous conditions. The attraction of DMAA-TMC, as a biodegradable and biocompatible copolymer, with SWCNT showed that degradation mechanism in acidic environment deformed the copolymer. This leads to a smart release mechanism in an acidic cancerous tissue. Additionally, it improves hydrophilicity, optimum nano-particle size, and cell cytotoxicity concerns.ConclusionsThe simulation results manifested a significant contribution of DMAA-TMC in the adsorption and release of cancer chemotherapy drugs in normal and neoplastic tissues. The interaction of copolymer also improves the biocompatibility and biodegradability of the SWCNT. Smart drug delivery carrier can be a valuable nanohybrid for loading, transporting, and releasing of cancer chemotherapy drugs.Graphical abstract

Carbon Dots: A Future Blood-Brain Barrier Penetrating Nanomedicine and Drug Nanocarrier.

Drug delivery across the blood–brain barrier (BBB) is one of the biggest challenges in modern medicine due to the BBB’s highly semipermeable property that limits most therapeutic agents of brain diseases to enter the central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types of CDs and CD-ligand conjugates have been reported successfully penetrating the BBB, which shows a promising progress in the application of CD-based drug delivery system (DDS) for the treatment of CNS diseases. In this review, our discussion of CDs includes their classification, preparations, structures, properties, and applications for the treatment of neurodegenerative diseases, especially Alzheimer’s disease (AD) and brain tumor. Moreover, abundant functional groups on the surface, especially amine and carboxyl groups, allow CDs to conjugate with diverse drugs as versatile drug nanocarriers. In addition, structure of the BBB is briefly described, and mechanisms for transporting various molecules across the BBB and other biological barriers are elucidated. Most importantly, recent developments in drug delivery with CDs as BBB-penetrating nanodrugs and drug nanocarriers to target CNS diseases especially Alzheimer’s disease and brain tumor are summarized. Eventually, future prospects of the CD-based DDS are discussed in combination with the development of artificial intelligence and nanorobots.

All-Polycarbonate Graft Copolymers with Tunable Morphologies by Metal-Free Copolymerization of CO2 with Epoxides

Brush-type macromolecules (BMs) have attracted much attention over the past decades because of their unique properties and potential applications in nanoscience, drug-delivery systems, and photonics. A two-step strategy of synthesis of polycarbonate-grafted copolymers with either star-shaped or brush-typed morphologies using a “grafting from” approach is reported; the backbone in these all-polycarbonate graft copolymers is made of poly(cyclohexene carbonate) (PCHC), and the side grafts are made of poly(propylene carbonate) (PPC). In the first step, poly (vinyl-cyclohexene carbonate) (PVCHC) backbones of two different sizes (PVCHC35, PVCHC283) were prepared by copolymerization of vinyl-cyclohexene oxide (VCHO) with CO2 in the presence of triethylborane (TEB), using tetrabutyl ammonium succinate (TBAS) as the initiator. In the second step, the dangling vinyl double bonds of PVCHC were transformed into carboxylic acid groups. After partial neutralization of the latter using tetrabutyl ammonium hydroxide, the PPC grafts could be grown from the backbone carboxylic sites by copolymerization of propylene oxide (PO) with CO2 in the presence of TEB. Before attempting the synthesis of the above all-polycarbonate grafted copolymers, we check the viability of the above synthetic strategy by preparing graft copolymers made of a polymethacrylate backbone and PPC side grafts. In the latter case, the backbone was generated by reversible addition–fragmentation chain-transfer (RAFT) polymerization of methacrylic acid (MAA), followed by the growth of PPC side grafts using the backbone carboxylates as initiating sites. In both cases (PVCHC-g-PPC and PMAA-g-PPC), two types of architectures corresponding to two different morphologies were synthesized: star-shaped morphologies were obtained from rather short backbones, and relatively long grafts, on the one hand, and semiflexible cylinders were grown from rather long backbones and short grafts. These various structures were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography/light scattering (GPC/LS), and their morphologies were further investigated by atomic force microscopy (AFM). The reported synthetic method provides a robust way to synthesize well-defined polycarbonates with either star-type or brush-type morphologies and graft copolymers made of polyacrylate backbones and polycarbonate grafts. Thermal and mechanical properties of these graft copolymers were also investigated.

Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels.

In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and physiological variability resulting in unsatisfactory therapeutic efficacy of lipophilic active substances requires application of multicompartment drug delivery systems. This manuscript provides an up-to-date comprehensive review of the literature on emulsion-based vaginal dosage forms (EVDF) including macroemulsions, microemulsions, nanoemulsions, multiple emulsions and self-emulsifying drug delivery systems. The first part of the paper discusses (i) the influence of anatomical-physiological conditions on therapeutic efficacy of drug forms after local and systemic administration, (ii) characterization of EVDF components and the manufacturing techniques of these dosage forms and (iii) methods used to evaluate the physicochemical and pharmaceutical properties of emulsion-based vaginal dosage forms. The second part of the paper presents (iv) the results of biological and in vivo studies as well as (v) clinical evaluation of EVDF safety and therapeutic efficacy across different indications.

A review of nanoparticle drug delivery systems responsive to endogenous breast cancer microenvironment

Breast cancer, as a malignant disease that seriously threatens women's health, urgently needs to be researched to develop effective and safe therapeutic drugs. Nanoparticle drug delivery systems (NDDS), provide a powerful means for drug targeting to the breast cancer, enhancing the bioavailability and reducing the adverse effects of anticancer drug. However, the breast cancer microenvironment together with heterogeneity of cancer, impedes the tumor targeting effect of NDDS. Breast cancer microenvironment, exerts endogenous stimuli, such as hypoxia, acidosis, and aberrant protease expression, shape a natural shelter for tumor growth, invasion and migration. On the basis of the ubiquitous of endogenous stimuli in the breast cancer microenvironment, researchers exploited them to design the stimuli-responsive NDDS, which response to endogenous stimulus, targeted release drug in breast cancer microenvironment. In this review, we highlighted the effect of the breast cancer microenvironment, summarized innovative NDDS responsive to the internal stimuli in the tumor microenvironment, including the material, the targeting groups, the loading drugs, targeting position and the function of stimuli-responsive nanoparticle drug delivery system. The limitations and potential applications of the stimuli-responsive nanoparticle drug delivery systems for breast cancer treatment were discussed to further the application.

Biodegradable polycaprolactone (PCL) based polymer and composites

Abstract Polycaprolactone (PCL) is a biodegradable polyester that has advantages over other biopolymers, making it an extensively researched polymer. PCL is a hydrophobic, slow-degrading, synthetic polymer making it particularly interesting for the preparation of long-term implantable devices and a variety of drug delivery systems. Recently, PCL has been used for additional applications including food packaging and tissue engineering. In this chapter, the processing methods and characterization of PCL will be discussed. The chapter will summarize the synthesis of poly(α-hydroxy acid) and the ring-opening polymerization of PCL. Discussion on the biodegradability of PCL will be reviewed. The biomedical applications of PCL, such as, drug-delivery systems, medical devices, and tissue engineering will be also summarized. Finally, the chapter will conclude with a characterization section outlining recent studies focusing on PCL based composites and films.

An overview of characterizations and applications of proniosomal drug delivery system

Proniosomal drug delivery system is a stable provesicular system in nanotechnology to overcome the drawbacks associated with other vesicular systems. These are water-soluble pro-vesicular drug carriers coated with a non-ionic surfactant which on hydration give niosomes. The system is encapsulated and shows a systemic and targeted delivery of poorly soluble drugs with increased bioavailability and decreased side effects. Here we have covered characterizations and applications of the proniosomal drug delivery system.

An overview of characterizations and applications of proniosomal drug delivery system

An overview of characterizations and applications of proniosomal drug delivery system

Preparation and characterization of dexamethasone loaded sodium alginate-graphene oxide microspheres for bone tissue engineering

Over 2.2 million bone graft transplantations are performed by clinicians worldwide annually. The development of synthetic bone graft substitute for the treatment of bone defects is still an utmost challenge in bone tissue engineering. In the current study, we have fabricated calcium ion cross-linked alginate (Alg), alginate-graphene oxide (Alg-GO) and alginate-graphene oxide-dexamethasone (Alg-GO-Dex) composite microspheres as an alternative bone graft substitute. Various properties of developed microspheres were investigated using appropriate characterization tools including Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy combined with energy dispersive X-ray diffraction. In vitro biomineralization study was performed using simulated body fluid (SBF) solution. Biocompatibility of the developed microspheres was studied with osteoblast-like cells (MG-63). The developed microspheres showed more than 80% of porosity and dispersion of GO in the alginate matrix was uniform. The size of developed microspheres is in the range of 1.5 ± 0.5 mm, and Dex drug was released from the microspheres in sustainable manner. Excellent apatite formation was observed on the surface of the microspheres using SBF solution which is useful for bone tissue regeneration. In vitro studies using osteoblast like MG-63 cells revealed profound biocompatibility. Thus, the developed Alg-GO-Dex composite microspheres have potential applications in drug delivery system towards bone tissue engineering applications.

Preparation of Azithromycin Nanofibers as Controlled Release Ophthalmic Drug Carriers Using Electrospinning Technique: In Vitro and In Vivo Characterization.

Purpose: Conventional topical dosage forms face with some challenges like low intraocularbioavailability, which could be overcome by application of novel drug delivery systems.Therefore, this study was conducted to prepare azithromycin (AZM)-loaded chitosan/polyvinylalcohol/polyvinyl pyrrolidone (CS/PVA-PVP) nanofibers with the prolonged antibacterialactivity by electrospinning method. Methods: After preparation of nanofibers, they were characterized in terms of physicochemicaland morphological properties. In vitro and in vivo release of the drug from nanofibers wereevaluated using microbial assay against the Micrococcus luteus. Antibacterial efficacy of thenanofibers was assessed. The ophthalmic irritation test was also performed. MTT test wascarried out to evaluate cytotoxicity of the formulations. Results: All the formulations were found to be stable with uniform thickness, weight, and drugcontent. Nanofibers had a diameter range from 119 ± 29 to 171 ± 39 nm. The inserts were nonirritantand non-toxic to the rabbits’ eye. Based on the obtained results, the crosslinked AZMnanofibers showed slower and more controlled drug release in tear fluid compared to the noncrosslinkedones, within 184 hours. Conclusion: Our results revealed that the prepared nanofibers could be considered as suitableand non-invasive inserts for the prolonged ophthalmic delivery of AZM.

A pH-sensitive curcumin loaded microemulsion-filled alginate and porous starch composite gels: Characterization, in vitro release kinetics and biological activity

To improve the controlled release and stability of the loaded drug, the alginate–porous starch solution, as the gel matrix (GM), was prepared and added into curcumin-loaded microemulsion (CUR-ME) in a certain proportion, and then mixed with slow-gelling agents (CaCO3 + d-glucono-δ-lactone) to prepared curcumin-loaded microemulsion gel (CUR-ME-G). With increasing the proportion of GM from 25% (CUR-ME3G1) to 83% (CUR-ME1G5), the drug loading efficiency increased from 24% to 98% and the maximum drug loading capacity (14.9 mg/g) was found in CUR-ME1G3 with 75% GM. Moreover, a denser structure that entrapped all microemulsion droplets was formed with increasing the proportion of microemulsion according to the observation of scanning electron microscopy. This was also confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy that no new peaks appeared in CUR-ME-G, while the hydrogen bonding interactions might exist between curcumin and sodium alginate. The in vitro release of the CUR-ME-G followed diffusion-controlled mechanism that was consistent with the first-order kinetic model. The release rate depended on the components of the CUR-ME-G and the pH value of the release medium. CUR-ME-G with curcumin concentration of 0.20% exhibited the best biological activity. CUR-ME-G might provide a potential application in the smart drug delivery systems.

Review of nanomembranes: materials, fabrications and applications in tissue engineering (bone and skin) and drug delivery systems

Review of nanomembranes: materials, fabrications and applications in tissue engineering (bone and skin) and drug delivery systems

TiO₂-Chitosan Hybrid Materials for Drug Delivery Applications: Conjugation Reaction with a Model Drug and Evaluation of the Functional Properties.

The combination of TiO₂ and chitosan is known to allow the achievement of implantable devices which combines the mechanical properties of TiO₂, with the presence of chitosan, which ensures antibacterial properties combined with an in-situ drug-delivery of biomolecules physisorbed and/or covalently linked to chitosan. In this study, 5-aminofluorescein (5-AF), a derivative of fluorescein containing a primary amino group, has been used as model molecule to simulate a drug. This dye is characterized by low cost and low toxicity, and due to its high molar absorptivity it can easily be detected by means of absorption and emission spectroscopies. The combination of 5-AF and maleic anhydride (MA) with TiO₂-chitosan materials has generated a range of novel hybrid materials tailored to applications in localized stimuli-responsive drug delivery systems. Maleic anhydride has been used as pH sensitive spacer for the covalent functionalization of the TiO₂-chitosan hybrid with MA as linker molecule. This functionalization allowed to obtain a pH-sensitive hybrid material. The efficiency of the functionalization has been verified by means of different physico-chemical characterization techniques. The behaviour of the functionalized materials is related to different parameters, among which the ratio between physisorbed/coordinated and chemisorbed 5-AF and the matrix degradation. Moreover, delivery tests in simulated body solutions at different pH have been performed showing a pH-sensitive drug delivery behaviour and indicating that the release of 5-AF is favoured at basic pH.