Triggered Drug Release Research Articles

Capric Acid and Myristic Acid Permeability Enhancers in Curved Liposome Membranes.

Liposomes are considered as advanced drug delivery systems for cancer treatment. A generation of pH-sensitive liposomes is being developed that use fatty acids (FAs) as a trigger for drug release in tumor tissues. However, FAs are also known to enhance permeability, and it is unclear whether FAs in liposomes may cause drug leakage or premature drug release. The passive permeability of the drug through the membrane of the liposome is thus a crucial factor for timely drug delivery. To investigate how the curvature and lipid composition of liposomes affect their passive permeability, coarse-grained molecular dynamics were performed. The permeability was determined with a counting method. Flat bilayers and three liposomes with varying diameters were studied, which had varying lipid compositions of dipalmitoylphosphatidylcholine, cholesterol, and deprotonated or neutral saturated FAs. The investigated permeants were water and two other small permeants, which have different free energy profiles (solubility) across the membrane. First, for the curvature effect, our results showed that curvature increases the water permeability by reducing the membrane thickness. The permeability increase for water is about a factor of 1.7 for the most curved membranes. However, a high curvature decreases permeability for permeants with free energy profiles that are a mix of wells and barriers in the headgroup region of the membrane. Importantly, the type of experimental setup is expected to play a dominant role in the permeability value, i.e., whether permeants are escaping or entering the liposomes. Second, for the composition effect, FAs decrease both the area per lipid (APL) and the membrane thickness, resulting in permeability increases of up to 55%. Cholesterol has a similar effect on the APL but has the opposite impact on membrane thickness and permeability. Therefore, FAs and cholesterol have opposing effects on permeability, with cholesterol's effect being slightly stronger in our simulated bilayers. As all permeability values were well within a factor of 2, and with liposomes usually being larger and less curved in experimental applications, it can be concluded that the passive drug release from a pH-sensitive liposome does not seem to be significantly affected by the presence of FAs.

A self-generated electricity-driven drug delivery system for precision management of myopia

Myopia presents a formidable challenge, especially in children, where clinical management involves the use of atropine and 7-methylxanthine, necessitating multiple doses, strong side effects and encountering suboptimal compliance due to children's resistance. In response to these issues, our research proposes a self-generated electricity-driven drug delivery system (EDDDS) designed for precision myopia treatment. The EDDDS intelligently releases therapeutic drugs, such as atropine, at ocular tissues using drug-coated nanogenerators, aiming to effectively slow down the progression of myopia. This system combines nanotechnology and smart drug delivery mechanisms to achieve controlled and responsive drug administration. The nanogenerators embedded in the EDDDS generate electric fields that trigger drug release upon closing eyes conditions, providing targeted treatment. Simultaneously, the weak voltage can effectively relieve the ciliary muscle, offering additional benefits for myopia management. In vitro and in vivo experiments have demonstrated the efficacy and potential of the EDDDS in precisely modulating myopia progression. The proposed EDDDS holds significant promise as an advanced and high-precision therapeutic approach for myopia management. Its potential to address the limitations of current treatments makes it a promising avenue for future research and clinical applications.

Development of Robust Cationic Light-Activated Thermosensitive Liposomes: Choosing the Right Lipids.

Extensive research has been conducted on cationic light-activated thermosensitive liposomes (CLTSLs) as a means for site-specific and controlled drug release; however, less attention has been given to the stability of these nanoparticles. Selecting the appropriate lipids is crucial for the development of a stable and responsive system. In this study, we investigated the impact of various lipids on the physical properties of cationic light-activated liposomes. Incorporating poly(ethylene glycol) PEG molecules resulted in uniform liposomes with low polydispersity index, while the addition of unsaturated lipid (DOTAP) resulted in extremely leaky liposomes, with almost 80% release in just 10 min of incubation at body temperature. Conversely, the inclusion of cholesterol in the formulation increased liposome stability too much and decreased their sensitivity to stimuli-responsive release, with only 14% release after 2 min of light exposure. To achieve stable and functional CLTSL, we substituted an equivalent amount of unsaturated lipid with a saturated lipid (DPTAP), resulting in stable liposomes at body temperature that were highly responsive to light, releasing 90% of their content in 10 s of light exposure. We also conducted two atomistic molecular dynamics simulations using lipid compositions with saturated and unsaturated lipids to investigate the effect of lipid composition on the dynamical properties of the liposomal lipid bilayer. Our findings suggest that the nature of lipids used to prepare liposomes significantly affects their properties, especially when the drug loading needs to be stable but triggered drug release properties are required at the same time. Selecting the appropriate lipids in the right amount is therefore essential for the preparation of liposomes with desirable properties.

Magnetic iron oxide nanoparticles@lecithin/poly (l-lactic acid) microspheres for targeted drug release in cancer therapy

The use of targeted chemotherapy is a promising solution to mitigate the side effects and dosage of drugs. This research focuses on the development of magnetic microspheres (MMS) based drug carriers for targeted chemotherapy, formulated with iron oxide nanoparticles (Fe3O4 NPs) and poly (l-lactic acid) (PLA) loaded with the antibiotic drug Ciprofloxacin (CIF). In this study, Fe3O4 NPs were synthesized using pomegranate peel extract as a natural reducing and stabilizing agent. The double emulsification method (W1/O/W2) was employed to produce Fe3O4@LEC-CIF-PLA-MMS, which were characterized using various spectral and microscopic techniques. The drug encapsulation efficiency for Fe3O4@LEC-CIF-PLA-MMS was found to be 80.7 %. The in vitro drug release of CIF from Fe3O4@LEC-CIF-PLA-MMS induced by H2O2 and GSH- stimuli was found to be 87.55 % and 82.32 %, respectively in acidic pH 4.5. Notably, the magnetically triggered drug release behaviour of Fe3O4@LEC-CIF-PLA-MMS (93.56 %) was assessed in acidic pH environment upon exposure to low-frequency alternating magnetic field (LF-AMF). Fe3O4@LEC-CIF-PLA-MMS demonstrated significantly enhanced in vitro cytotoxicity (IC50 = 0.8 ± 0.03 μg/mL) against the HeLa-S3 cancer cell lines. Nevertheless, these research findings highlight the potential of Fe3O4@LEC-CIF-PLA-MMS for further development as a chemotherapeutic agent and hold promise for the future of targeted cancer treatment.

Magnetothermal spider silk-based scaffolds for cartilage regeneration

Developing biocompatible, magnetically controlled polymers is a multifunctional solution to many surgical complications. By combining nanoparticle technology with the latest advancements in polymer materials science, we created a multicomponent hybrid system comprised of a robust native spider silk-based matrix; a Mn0.9Zn0.1Fe2O4 nanoparticles coating to provide a controlled thermal trigger for drug release; and liposomes, which act as drug carriers. Fluorescent microscope images show that the dye loaded into the liposomes is released when the system is exposed to an alternating magnetic field due to heating of ferromagnetic nanoparticles, which had a low Curie temperature (40–46°С). The silk matrix also demonstrated outstanding biocompatibility, creating a favorable environment for human postnatal fibroblast cell adhesion, and paving the way for their directed growth. This paper describes a complex approach to cartilage regeneration by developing a spider silk-based scaffold with anatomical mechanical properties for controlled drug delivery in a multifunctional autologous matrix-induced chondrogenesis.

Critical Design Strategies Supporting Optimized Drug Release from Polymer-Drug Conjugates.

The importance of an adequate linking moiety design that allows controlled drug(s) release at the desired site of action is extensively studied for polymer-drug conjugates (PDCs). Redox-responsive self-immolative linkers bearing disulfide moieties (SS-SIL) represent a powerful strategy for intracellular drug delivery; however, the influence of drug structural features and linker-associated spacers on release kinetics remains relatively unexplored. The influence of drug/spacer chemical structure and the chemical group available for conjugation on drug release and the biological effect of resultant PDCs is evaluated. A "design of experiments" tool is implemented to develop a liquid chromatography-mass spectrometry method to perform the comprehensive characterization required for this systematic study. The obtained fit-for-purpose analytical protocol enables the quantification of low drug concentrations in drug release studies and the elucidation of metabolite presence. and provides the first data that clarifies how drug structural features influence the drug release from SS-SIL and demonstrates the non-universal nature of the SS-SIL. The importance of rigorous linker characterization in understanding structure-function correlations between linkers, drug chemical functionalities, and in vitro release kinetics from a rationally-designed polymer-drug nanoconjugate, a critical strategic crafting methodology that should remain under consideration when using a reductive environment as an endogenous drug release trigger.

Prototype of a Coupling Device to Investigate Focused Ultrasound-Induced Inertial Cavitation for Drug Delivery Applications

Abstract Focused ultrasound (FUS) can be used as a drug delivery application for localized chemotherapy to treat cancer. The effect of ultrasound-induced inertial cavitation is promising to trigger drug release from nanocarriers. To investigate this effect, usually, a passive cavitation detection setup is employed. However, applying such a setup is challenging for in vivo experiments, as the test object may need to be fixed inside the water tank. Thus, we present a prototype of a coupling device that could significantly simplify experiments. Since this setup favors undesired sound wave interference and their resulting exceedance of the Mechanical Index, we additionally investigated different signal lengths. The occurrence of standing waves at a signal length of 44 cycles can both be derived from a changing cavitation activity and our calculations. The appearing interference also results in a mean increase of the cavitation activity by ≈ 5.1 %, verified by our experiments as well.

Combination therapy to overcome ferroptosis resistance by biomimetic self-assembly nano-prodrug

Ferroptosis has emerged as a potent form of no-apoptotic cell death that offers a promising alternative to avoid the chemoresistance of apoptotic pathways and serves as a vulnerability of cancer. Herein, we have constructed a biomimetic self-assembly nano-prodrug system that enables the co-delivery of gefitinib (Gefi), ferrocene (Fc) and dihydroartemisinin (DHA) for the combined therapy of both ferroptosis and apoptosis. In the tumor microenvironment, this nano-prodrug is able to disassemble and trigger drug release under high levels of GSH. Interestingly, the released DHA can downregulate GPX4 level for the enhancement of intracellular ferroptosis from Fc, further executing tumor cell death with concomitant chemotherapy by Gefi. More importantly, this nano-prodrug provides highly homologous targeting ability by coating related cell membranes and exhibits outstanding inhibition of tumor growth and metastasis, as well as no noticeable side-effects during treatments. This simple small molecular self-assembled nano-prodrug provides a new reasonably designed modality for ferroptosis-combined chemotherapy.

Scintillating and magnetic stimuli-responsive nanostructures as adjuvants in cancer therapy

We present an overview of recent advances in stimuli-responsive nanostructures for medicine and drug delivery aiming at improving the efficacy and minimizing side effects of cancer therapies. We focus on two complementary system: Self-Lighted Photodynamic Therapy (SLPDT), and magnetic systems for hyperthermia and for controlled drug release. SPLDT, also known as X-ray triggered PDT, bases on hybrid nanostructures such as functionalized SiC/SiOx nanowires and CeF3/ZnO nanostructures. We emphasize the importance of discriminating the various Reactive Oxygen Species (ROS) produced, i.e., singlet oxygen, peroxide, superoxide, and hydroxyl radicals, which have different effects on cells and different therapeutic efficacy. Singlet oxygen is quantified by an ad hoc NIR fluorimeter. SLPDT can be usefully complemented by smart systems responsive to magnetic fields. As examples, we discuss the use of superparamagnetic iron oxide nanoparticles for magnetic hyperthermia and magnetic nanocapsules for triggered drug release. Finally, we highlight promising directions for future developments.

Improving cancer chemotherapy through photothermally triggered drug release from poly(N-isopropylacrylamide-co-acrylic acid)/Prussian blue hydrogel

Recently, microgel-based drug delivery systems have received great attention. However, these systems face various challenges such as low drug loading, leakage, rapid drug elimination by the bloodstream, and low efficacy against tumors. To overcome these limitations, we fabricated a near-infrared (NIR)-responsive poly(N-isopropylacrylamide-co-acrylic acid)/Prussian blue microgel (PNA@PB). The microgel featured improved stability and higher loading of Prussian blue (PB), achieved by chemically linking it to the polymer. For cancer therapy, the microgel was loaded with the model drug doxorubicin (DOX) to obtain PNA@PB@DOX, resulting in a high loading capacity of 26% and encapsulation efficiency of 51%. Upon exposure to 808 nm NIR laser light, the photothermal PB in PNA@PB@DOX raised the temperature above the lower critical solution temperature of the microgel, causing the microgel to shrink and release the drug by 36%. The NIR-triggered drug release by PNA@PB@DOX resulted in improved photothermal/chemotherapy performance, both in vitro and in vivo experiments using A549 lung cancer cells, compared with PNA@PB. The combination of photothermal therapy from PB and photothermal shrinkage-induced chemotherapy from PNA was found to be highly effective in killing cancer cells.

A short review on the applicability and use of cubosomes as nanocarriers.

Cubosomes are nanostructured lipid-based particles that have gained significant attention in the field of drug delivery and nanomedicine. These unique structures consist of a three-dimensional cubic lattice formed by the self-assembly of lipid molecules. The lipids used to construct cubosomes are typically nonionic surfactants, such as monoolein, which possess both hydrophilic and hydrophobic regions, allowing them to form stable, water-dispersible nanoparticles. One of the key advantages of cubosomes is their ability to encapsulate and deliver hydrophobic as well as hydrophilic drugs. The hydrophobic regions of the lipid bilayers provide an ideal environment for incorporating lipophilic drugs, while the hydrophilic regions can encapsulate water-soluble drugs. This versatility makes cubosomes suitable for delivering a wide range of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids. The unique structure of cubosomes also offers stability and controlled release benefits. The lipid bilayers provide a protective barrier, shielding the encapsulated drugs from degradation and improving their stability. Moreover, the cubic lattice arrangement enables the modulation of drug release kinetics by varying the lipid composition and surface modifications. This allows for the development of sustained or triggered drug release systems, enhancing therapeutic efficacy and reducing side effects. Furthermore, cubosomes can be easily modified with targeting ligands or surface modifications to achieve site-specific drug delivery, enhancing therapeutic selectivity and reducing off-target effects. In conclusion, cubosomes offer a versatile and promising platform for the delivery of therapeutic agents. In this manuscript, we will highlight some of these applications.

Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

Applications of MOFs in Drug Delivery

The main research focus of this article is the application of Metal-Organic Frameworks (MOFs) in drug delivery applications. The review primarily concentrates on the methods used for loading drugs into MOFs, their response to stimuli, potential applications, and limitations. The article begins with discussing the limitations of traditional drug delivery systems and introduces MOFs as a potential solution to these limitations. The drug loading strategy section describes the three main methods for loading drugs into MOFs, including their respective benefits and drawbacks. The stimulus response release program section explores various stimuli that can trigger drug release from MOFs, including physical, chemical, and biological factors, and provides examples of how MOFs can respond to these stimuli. The section on application and challenges provides an overview of current studies exploring the potential of MOFs in biomedical applications, including cancer therapy, antibacterial therapy, and anti-inflammatory therapy, while also highlighting the key challenges facing MOFs research, such as biocompatibility and toxicity. Finally, the article concludes by offering prospects for future developments in MOFs research. This review article provides a significant resource for drug delivery researchers and practitioners who wish to investigating the possibility of utilizing MOFs as novel drug delivery vehicles.

Bioreducible exosomes encapsulating glycolysis inhibitors potentiate mitochondria-targeted sonodynamic cancer therapy via cancer-targeted drug release and cellular energy depletion

Nanocarrier-assisted sonodynamic therapy (SDT) has shown great potential for the effective and targeted treatment of deep-seated tumors by overcoming the critical limitations of sonosensitizers. However, in vivo SDT using nanocarriers is still constrained by their intrinsic toxicity and nonspecific cargo release. In this study, we developed bioreducible exosomes for the safe and tumor-specific delivery of mitochondria-targeting sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (T-Ce6)] and glycolysis inhibitors (FX11). Redox-cleavable diselenide linker-bearing lipids were embedded into exosomes to trigger drug release in response to overexpressed glutathione in the tumor microenvironment. Bioreducible exosomes facilitate the cytoplasmic release of their payload in the reducing environment of tumor cells. They significantly enhance drug release and sonodynamic effects when irradiated with ultrasound (US). The mitochondria-targeted accumulation of T-Ce6 efficiently damaged the mitochondria of the cells under US irradiation, accelerating apoptotic cell death. FX11 substantially inhibited cellular energy metabolism, potentiating the antitumor efficacy of mitochondria-targeted SDT. Bioreducible exosomes effectively suppressed tumor growth in mice without significant systemic toxicity, via a combination of mitochondria-targeted SDT and energy metabolism-targeted therapy. This study offers new insights into the use of dual stimuli-responsive exosomes encapsulating sonosensitizers for safe and targeted sonodynamic cancer therapy.

X-ray-induced Drug Release for Cancer Therapy.

Drug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug-loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release. However, conventional light sources primarily concentrate on the ultraviolet (UV) and visible light regions, which suffer from limited biological tissue penetration. This limitation hinders applications for deep-tissue tumor drug release. Given their deep tissue penetration and well-established application technology, X-rays have recently received attention for the pursuit of controlled drug release. With precise spatiotemporal and dosage controllability, X-rays stand as an ideal stimulus for achieving controlled drug release in deep-tissue cancer therapy. This article explores the recent advancements in using X-rays for stimulus-triggered drug release in DDSs and delves into their action mechanisms.

X‐Ray‐Induced Drug Release for Cancer Therapy

AbstractDrug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug‐loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release. However, conventional light sources primarily concentrate on the ultraviolet (UV) and visible light regions, which suffer from limited biological tissue penetration. This limitation hinders applications for deep‐tissue tumor drug release. Given their deep tissue penetration and well‐established application technology, X‐rays have recently received attention for the pursuit of controlled drug release. With precise spatiotemporal and dosage controllability, X‐rays stand as an ideal stimulus for achieving controlled drug release in deep‐tissue cancer therapy. This article explores the recent advancements in using X‐rays for stimulus‐triggered drug release in DDSs and delves into their action mechanisms.

A biocompatible adenine-based metal–organic framework for Ca2+ responsive drug delivery

An anionic zinc-adeninate MOF ZJU-64-NH2 has been successfully fabricated by solvothermal method. The high crystallinity of ZJU-64-NH2 was confirmed through powder X-ray diffraction (PXRD) analysis. The cationic model drug procainamide (PA) was efficiently encapsulated into ZJU-64-NH2 through electrostatic interaction, and its loading capacity was determined to be 12.97 wt%. The drug delivery system PA@ZJU-64-NH2 exhibited Ca2+-triggered drug release due to ion exchange, indicating promising potential for bone tumor therapy. The excellent biocompatibility of ZJU-64-NH2 was demonstrated through MTT assay and confocal microscopy imaging.

A cascade-responsive nanoplatform with tumor cell-specific drug burst release for chemotherapy.

Most of the nanomedicines can reduce the side effects of anti-tumor chemical drugs but do not have good enough therapeutic efficacy, largely due to the sustained drug release profile. It might be a promising alternative strategy to develop a cascade-responsive nanoplatform against tumor with the burst release of chemotherapeutics based on the highly efficient tumor cell targeting delivery. In this work, we constructed innovative nanoparticles (PMP/WPH-NPs) consisting of two functional polymers. PMP contained the MMP-2 enzyme sensitive linker and disulfide bond, which could respond to the tumor-overexpressing enzyme MMP-2 and high-level glutathione. While WPH promoted tumor penetration and acid-responsive drug release by modifying cellular penetrating peptides and polymerizing L-histidine. PMP/WPH-NPs exhibited outstanding features including longer blood circulation time, promoted tumor-specific accumulation, enhanced tumor penetration and efficient escape from lysosomes. Subsequently, the model drug paclitaxel (PTX), widely used in the tumor chemotherapy, was encapsulated into PMP/WPH-NPs via an emulsion solvent evaporation method. Within a short period of time, PTX-PMP/WPH-NP in simulated tumor cellular microenvironment could release 8 times more PTX than that in the physiological environment, demonstrating a good potential in tumor cell-specific burst drug release. In addition, PTX-PMP/WPH-NPs exhibited stronger anti-tumor activity than PTX in vitro and in vivo, which also had good biocompatibility according to the hemolysis assay and H&E staining. In summary, our work has succeeded in designing an original polymeric nanoplatform for programmed burst drug release based on the tailored tumor targeting delivery system. This new approach would facilitate the clinical translation of more anti-tumor nanomedicines. STATEMENT OF SIGNIFICANCE: Biomaterials responsive to the tumor-specific stimulus has conventionally used in the targeted-delivery of anti-tumor drugs. However, the levels of common stimulus are not uniformly distributed and not high enough to effectively trigger drug release. In an effort to achieve a better specific drug release and promote the chemotherapeutic efficacy, we constructed a cascade responsive nanoplatform with tumor cell-specific drug burst release profile. The tailored biomaterial could overcome the bio-barriers in vivo and succeeded in the programmed burst drug release based on the tumor cell-specific delivery of chemotherapeutics.

Metal-Organic Framework in Pharmaceutical Drug Delivery.

Metal-organic frameworks (MOFs) are porous, crystalline materials made up of organic ligands and metal ions/metal clusters linked by coordinative bonds. This large family is becoming increasingly popular for drug delivery due to their tuneable porosity, chemical composition, size and shape, and ease of surface functionalization. There has been a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. Starting with the MOFs classification adapted for drug delivery systems (DDSs) based on the types of constituting metals and ligands. MOFs are appealing drug delivery vehicles because of their substantial drug absorption capacity and slow-release processes, which protect and convey sensitive drug molecules to target areas. Other guest materials have been incorporated into MOFs to create MOF-composite materials, which have added additional functionalities such as externally triggered drug release, improved pharmacokinetics, and diagnostic aids. Magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that increase blood circulation time are examples of synthetically adaptable MOF-composites. By including photosensitizers, which exert lethal effects on cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2), metalorganic frameworks have been employed for photodynamic treatment (PDT) of malignancies among a multitude of nanosized therapies. Importantly, a variety of representative MOF applications are described from the perspectives of pharmaceutics, disease therapy, and advanced drug delivery systems. However, because of their weak conductivity, selectivity, and lack of modification sites, MOF materials' uses in electrochemical biosensing are restricted. MOF-based composites provide excellent electrical conductivity and robust catalytic activity by adding functionalized nanoparticles into MOF structures, which process benefits over single component MOFs.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60–70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4–0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon’s tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.