Delivery Systems For Bioactive Compounds Research Articles

Development of Microemulsions<i> </i>Containing<i> Carthamus tinctorius</i> Extract for 5α-Reductase Inhibition

The purpose of this study was to develop micromeulsion consisting of Carthamus tinctorius floret extract (CT) as an ingredient to inhibit 5α-reductase activity. CT was extracted using a simple maceration technique with ethanol and inhibition of 5α-reductase activities was determined. Solutions of 2% CT extract were loaded into four microemulsion (ME) formulas (F1, F2, F3 and F4) and investigated for their physical properties, skin permeation and stability. Results showed that crude CT extract had no toxic effects on DU145 cells at concentrations of 0.0001-1.0 mg/mL. For reduction of 5α-reductase activities, concentration of CT extract at 0.05 mg/mL exhibited highest 5-reductase type-1 inhibition activity on the DU-145 cell line at 89.96% of the control, higher than standard finasteride (31.39%) and dutasteride (38.58%). The results indicated that a thermodynamically stable microemulsion improved the stability and permeation rate of CT extract. Among the ME formula, F3 was most appropriate for ME formulation with highest permeation rate and good stability during 30 days of storage. Therefore, using nanotechnology for stable transdermal delivery systems of bioactive compounds from Thai medicinal plants is one approach to improve skin and hair follicle permeation.

Mapping the location of DATEM in multi-phase systems: Synthesis and characterization of spin-label probe analogues

Electron paramagnetic resonance (EPR) spectroscopy has emerged as a fast, reliable, non-invasive and sensitive method to determine the distribution, localization and reactivity of labelled ingredients in micro-heterogeneous systems. However, the commercially available probe molecules are very limited. In the present work, five new nitroxide [(4-hydroxy-2, 2, 6, 6-tetramethylpiperidin-1-oxyl (TEMPOL)] derivatives (1b–5b) of diacetyl tartaric acid esters of monoglycerides (DATEM) (1a–5a), a widely used food emulsifier, were synthesized under Steglich conditions and characterized by MS (mass-spectrometry), FT-IR (Fourier-transform infrared spectroscopy), EPR, NMR (nuclear magnetic resonance spectroscopy), fluorescence spectroscopy, and DSC (differential scanning calorimetry) analysis. Phase partitioning studies proved that the new spin labels are adequately capable of describing the localizations and partitioning of the corresponding DATEM in multi-phase systems. Findings disclosed in this work will provide new knowledge on ingredient reactivity and localization in multi-phase systems; which is vital to aid the design of more efficient delivery systems for bioactive compounds.

Properties of Ternary Biopolymer Nanocomplexes of Zein, Sodium Caseinate, and Propylene Glycol Alginate and Their Functions of Stabilizing High Internal Phase Pickering Emulsions

A pH-cycle method based on preparing an alkaline solution of zein followed by neutralization with an acid can be used to prepare zein nanoparticles. In the present work, partial alkaline hydrolysis of propylene glycol alginate (PGA) to a lower pH was studied to prepare binary zein-PGA nanocomplexes and ternary complexes with additional sodium caseinate (NaCas). 0.5% or more PGA was sufficient to reduce the pH to 7.5 or lower, eliminating the need for titration, and resulted in simultaneous nanocomplex formation. The addition of NaCas into alkaline zein-PGA solution resulted in smaller complexes with all biopolymers, whereas adsorption on binary zein-PGA complexes was observed when NaCas was added into the neutral zein-PGA dispersions. The formation of nanocomplexes involved with hydrophobic and electrostatic attractions and hydrogen bonds and was further affected by the amount of NaCas. The ternary nanocomplexes with equal masses of zein and NaCas had an excellent capacity to prepare gel-like Pickering emulsions with as much as 80% v/v oil with characteristics suitable for texture modification and delivery systems of bioactive compounds in food and consumer products. Therefore, PGA can be used to possibly scale-up the pH-cycle method to produce zein-based nanoparticles with unique functional properties.

Multilayer biopolymer/poly(ε-caprolactone)/polycation nanoparticles

Combining two or more materials for carrier construction is one of the topical approaches to avoid/diminish deficiencies and to increase functionality in delivery systems for bioactive compounds. In this context, here, multilayered nanoparticles comprising both natural (atelocollagen—AteCol; hyaluronic acid derivative—HA) and synthetic [poly(e-caprolactone)—PCL; polyethylenimine—PEI; poly(l-lysine)—PLL] polymers were prepared and characterized. The combination of a modified double-emulsion method with polymer modification reactions allowed improvement of the polymer particle’s functionality. Fourier transform infrared spectroscopy (FTIR), UV–Vis spectroscopy, fluorescence spectroscopy, dynamic light scattering, transmission/scanning electron microscopy and fluorescence microscopy investigations confirmed the obtention of the envisaged nanomaterials with the expected composition and structure. The double-layered biopolymer/PCL-based nanoparticles formed in a first synthesis step could be successfully coated with PEI and PLL. The gel electrophoresis assay attested the DNA packing ability of the formed nano-vehicles involving surface grafting of the former biopolymer/PCL-based nanoparticles in the case of both cationic polymers, for N/P ratios of 10 (PEI coating) and 3.5 (PLL coating), respectively. According to the FTIR registration, the protein’s native form was preserved. Considering the advantage of biocompatibility and high versatility (controlled size, tuned chemistry and biodegradation rate) some of the resulted nanomaterials may appear as potential candidates for biomedical uses (i.e., drug/gene delivery and tissue engineering).

Formation of biopolymer complexes composed of pea protein and mesquite gum – Impact of quercetin addition on their physical and chemical stability

The purpose of this study was to prepare and evaluate the chemical and physical properties of protein-polyphenol-polysaccharide ternary soluble complexes composed of pea protein isolate (PPI), quercetin (Q) and mesquite gum (MG). PPI and MG were mixed in varying ratios at pH 5.0 and hydrodynamic diameter, ζ-potential, turbidity and soluble complexes yield were used to identify the optimal PPI:MG ratio (1:3 PPI:MG). A pH range of 3.0–7.0 was tested to find the optimal pH to form the soluble complexes using the previously mentioned ratio. Turbidity, hydrodynamic diameter and ζ-potential measurements were used for establishing the optimal pH (5.0) leading to the formation of soluble complexes which exhibited a hydrodynamic diameter of 333 ± 15 nm and ζ-potential of −19.00 ± 0.20 mV. The binding constant and number of binding sites of Q with PPI determined by fluorescence were 10.007 × 104 M−1 and 1.095 at 25 °C, respectively. Ternary complexes between PPI-Q-MG had a hydrodynamic diameter of 134 ± 7 nm, ζ-potential of −19.65 ± 0.21 mV, encapsulation efficiency of 89.83 ± 0.24%, scavenging activity of 36.09 ± 1.38% measured by ABTS, provided strong protection against UV-light degradation, and exhibited high physical stability during 28 days at 4 °C. The present work revealed that ternary complexes could be an effective delivery system for bioactive compounds with applications in a wide range of functional foods and beverages.

Ribbon-like Foldamers for Cellular Uptake and Drug Delivery.

Different intracellular delivery systems of bioactive compounds have been developed, including cell-penetrating peptides. Although usually nontoxic and biocompatible, these vectors share some of the general drawbacks of peptides, notably low bioavailability and susceptibility to protease degradation, that limit their use. Herein, the conversion of short peptide sequences into poly-α-amino-γ-lactam foldamers that adopt a ribbon-like structure is investigated. This template is used to distribute critical cationic and/or hydrophobic groups on both sides of the backbone, leading to potent short, cell-permeable foldamers with a low positive-charge content. The lead compound showed dramatically improved protease resistance and was able to efficiently deliver a biologically relevant cargo inside cells. This study provided a simple strategy to convert short peptide sequences into efficient protease-resistant cell-penetrating foldamers.

Evaluation of non-covalent ternary aggregates of lactoferrin, high methylated pectin, EGCG in stabilizing β-carotene emulsions

The present study explored the potential of ternary aggregates composed of lactoferrin (LF), high methylated pectin (HMP) and EGCG in stabilizing β-carotene emulsions. Different ternary aggregates were fabricated by mixing the three components in different sequences, followed by spray drying. Fluorescence measurement and FTIR analysis indicated that ternary aggregates and LF-HMP binary complex were formed mainly through hydrogen bonding and hydrophobic interactions. The mixing sequences of three components and the spray drying process resulted in different structures of ternary aggregates. When applied to stabilizing β-carotene emulsions, ternary aggregates were effective in retarding droplet aggregation and creaming, and protecting β-carotene from degradation, compared to the binary complexes of LF, HMP or EGCG. The least loss of β-carotene was observed in the emulsions stabilized by spray-dried ternary aggregates. The conclusion obtained from the present study would be useful in the development of novel delivery systems for bioactive compounds.

Fate of edible solid lipid nanoparticles (SLN) in surfactant stabilized o/w emulsions. Part 2: Release and partitioning behavior of lipophilic probes from SLN into different phases of o/w emulsions

The release and partitioning of encapsulated compounds from solid lipid nanoparticles (SLN) to other matrix constituents was investigated in o/w emulsions stabilized by different surfactants (CTAB, SDS, Tween 20) by confocal laser scanning microscopy (CLSM) and electron paramagnetic resonance spectroscopy (EPR) spectroscopy. CLSM images revealed that the encapsulated probe Coumarin 6 (C6) was located in the oil droplets after SLN were mixed with the different emulsions. The EPR spin probe TEMPOL‐benzoate (TB) showed different dynamics as a function of its specific solubilization sites in SLN. Four different populations of the spin probe could be separated giving the smallest population in the aqueous environment and the major population at the SLN interface. Two further populations were associated with differently crystalized lipid environments. This implies that both loosely structured regions with α- and β’-polymorphs and environments of β-polymorphs are present in SLN. In separated model emulsion systems, a prolonged release of TB from SLN was evident which predominately originated from the SLN interface. The released TB partitioned into the oil phase (25%) and into the o/w interface (30–45%), regardless of the presence or absence of additional surfactant micelles. Hence, these edible SLN may be used as delivery system for bioactive compounds in food emulsions with low impact of the surfactant used to stabilize the emulsion. The partial redistribution of the encapsulated compounds should be taken into account, but can also offer benefits when a prolonged release of lipophilic additives is desired.

Simultaneous treatment of heat and high pressure homogenization of zein in ethanol–water solution: Physical, structural, thermal and morphological characteristics

Abstract The effects of high pressure homogenization (HPH) and/or heat treatment on the physical, structural, thermal and morphological characteristics of zein in ethanol–water solution were investigated. The results showed that HPH significantly reduced the size of zein nanoparticles. Both of HPH and heat treatment resulted in the increase of ultraviolet absorption and fluorescence intensity, as well as the enhanced thermal stability of zein. Compared with the individual HPH and thermal treatment, the coupled treatment of heat and HPH induced more obvious changes on the secondary structure of zein with the α-helix content increasing from 49.2% to 67.1%. The morphology of zein was greatly modified from sphericity to oval, dumbbell-like and random geometrical shape after HPH at 125 MPa. The synergistic effect was found between thermal treatment and HPH at 75 MPa, which resulted in size reduction of zein nanoparticles with the spherical shape and uniform distribution. Industrial relevance Thermal treatment has been extensively applied to modify the physiochemical properties of water soluble proteins like β-lactoglobulin, lactoferrin and livetins. However, the available reports on the heat-induced structural and physicochemical changes of alcohol-soluble proteins are limited. Nowadays, the new insight into protein modification is to apply physical treatments such as high pressure homogenization (HPH). HPH has been applied to modify the physiochemical, functional and structural properties of water soluble proteins, including faba bean protein, whey proteins, peanut proteins and soy protein isolate. However, little information is available about the effect of HPH treatment on structural modifications of alcohol-soluble proteins. Besides, according to the previous literatures, the combined treatment of thermal with HPH is commonly employed to improve the stability of dairy products. Nevertheless, to our best knowledge, there is no report about the coupled treatment of thermal and HPH on the modification of ethanol-soluble protein. Results from present work can be used to confirm the hypothesis that the simultaneous treatment of thermal and HPH would be an attractive modification method for zein with better thermal behaviors and structural properties to develop new food grade materials, which could be useful in the development of the potential delivery systems for bioactive compounds.

Gel-like pea protein Pickering emulsions at pH 3.0 as a potential intestine-targeted and sustained-release delivery system for β-carotene

In recent years, there is increasing interest in the development of food-grade Pickering emulsions as promising delivery systems for bioactive compounds. Our previous work reported that most of the proteins in pea protein isolate (PPI) at pH3.0, present in the nanoparticle form, can effectively perform as a kind of food-grade Pickering stabilizers for oil-in-water emulsions (LWT, 2014). The purpose of this study was to further report that PPI-stabilized emulsions at pH3.0 exhibited great potential to act as intestine-targeted and sustained-release delivery systems for β-carotene. The emulsions were produced by microfluidization at a specific protein concentration of 6.0% (w/v) and varying oil fractions (ϕ) of 0.2–0.6. The results indicated that increasing ϕ was favorable for the gel-like network strengthening of these emulsions. The gel formation was largely related to the droplet flocculation as well as inter-floc attractive interactions. The in vitro simulated digestion results showed that the release of β-carotene during the intestinal digestion of these emulsions could be well modulated by altering ϕ. The gel-like emulsion at ϕ=0.6 exhibited much lower release of β-carotene, but higher stability towards degradation during the digestion, than that at ϕ=0.3. The findings provide important information not only for the design of novel delivery systems for lipophilic bioactive components, but also for the development of plant protein-based formulations.

Modulating the morphology of hydrogel particles by thermal annealing: mixed biopolymer electrostatic complexes

Biopolymer hydrogel particles formed by electrostatic complexation of proteins and polysaccharides have various applications within the food and other industries, including as delivery systems for bioactive compounds, as texture modifiers, and as fat replacers. The functional attributes of these electrostatic complexes are strongly influenced by their morphology, which is determined by the molecular interactions between the biopolymer molecules. In this study, electrostatic complexes were formed using an amphoteric protein (gelatin) and an anionic polysaccharide (pectin). Gelatin undergoes a helix-to-coil transition when heated above a critical temperature, which impacts its molecular interactions and hydrogel formation. The aim of this research was to study the influence of thermal annealing on the properties of hydrogel particles formed by electrostatic complexation of gelatin and pectin. Hydrogel particles were fabricated by mixing 0.5 wt% gelatin and 0.01 wt% pectin at pH 10 (where both were negatively charged) at various temperatures, followed by acidification to pH 5 (where they have opposite charges) with controlled acidification and stirring. The gelation () and melting temperature () of the electrostatic complexes were measuring using a small amplitude oscillation test: °C and °C. Three annealing temperatures (5, 30 and 50 °C) corresponding to different regimes (, , and ) were selected to control the configuration of the gelatin chain. The effects of formation temperature, annealing temperature, and incubation time on the morphology of the hydrogel particles were characterized by turbidity, static light scattering, and microscopy. The results of this study will facilitate the rational design of hydrogel particles with specific particle dimensions and morphologies, which has important implications for tailoring their functionality for various applications.

Food-grade protein-based nanoparticles and microparticles for bioactive delivery: fabrication, characterization, and utilization.

Proteins can be used to fabricate nanoparticles and microparticles suitable for use as delivery systems for bioactive compounds in pharmaceutical, food, cosmetic, and other products. Food proteins originate from various animal or vegetal sources and exhibit a wide diversity of molecular and physicochemical characteristics, e.g., molecular weight, conformation, flexibility, polarity, charge, isoelectric point, solubility, and interactions. As a result, protein particles can be assembled using numerous different preparation methods, from one or more types of protein or from a combination of a protein and another type of biopolymer (usually a polysaccharide). The final characteristics of the particles produced are determined by the proteins and/or polysaccharides used, as well as the fabrication techniques employed. This chapter provides an overview of the functional properties of food proteins that can be used to assemble nanoparticles and microparticles, the fabrication techniques available to create those particles, the factors that influence their stability, and their potential applications within the food industry.

Biopolymer nanoparticles as potential delivery systems for anthocyanins: Fabrication and properties

Biopolymer nanoparticles and microparticles may be used as delivery systems for bioactive compounds in food and pharmaceutical applications. In this study, biopolymer nanoparticles were assembled from whey protein isolate (WPI) and beet pectin (BP) using thermal processing and electrostatic complexation. This approach involved mixing the two biopolymers at pH5.8, heating (90°C, 5min) to induce protein nanoparticle formation and then adjusting the solution to pH4.0 to promote coating of the protein nanoparticles with pectin. This process led to the formation of relatively small anionic biopolymer nanoparticles (d<200nm) at pH4. The biopolymer particles had a high negative charged from pH8 to 4.0 but became less anionic at lower pH values. The mean particle diameter was relatively small (d<200nm) around pH4.0 but increased appreciably at lower and higher pH due to particle flocculation. The biopolymer nanoparticles were loaded with an anthocyanin-rich extract. A higher loading efficiency was observed when anthocyanin was added before heating the WPI-BP solution (LE=55%) rather than after (LE=35%), which was attributed to increased protein–polyphenol interactions. The encapsulation of anthocyanins within biopolymer particles improved their heat stability. However, encapsulated anthocyanin had a lower antioxidant activity than non-encapsulated anthocyanin, which was attributed to the thermal processing step required during particle fabrication and the binding of anthocyanins to biopolymers within the nanoparticles. Color measurements indicated that the encapsulation of anthocyanin within biopolymer particles did not inhibit its degradation after ascorbic acid addition. Overall, our results show that the encapsulation of anthocyanins within the biopolymer particles fabricated in this study was not particularly effective at improving their antioxidant activity or color stability. Alternative strategies are therefore needed to encapsulate this important color and nutraceutical agent.

Processes improving the dispersibility of spray-dried zein nanoparticles using sodium caseinate

Zein has been studied as a versatile food biopolymer to fabricate nanoparticles for encapsulating a large variety of bioactive compounds. Being water-insoluble prolamines, dispersing zein nanoparticles in aqueous systems is a challenge. Recently, sodium caseinate (NaCas) was observed to have improved the dispersibility of freeze-dried zein nanoparticles but not for spray-dried samples. In this paper, three different approaches were studied to produce spray-dried zein nanoparticles precipitated by dispersing aqueous ethanol solutions of zein into the aqueous phase. The control (S2) was produced by dispersing zein solution into NaCas dispersion without pH adjustment. The other two approaches involved conditions dissociating NaCas: adjusting NaCas dispersion to pH 11.0 (S5) or dissolving NaCas in heated zein solution before dispersing to a pH 8.0 buffer (S4). After hydrating the spray-dried powder, dispersions demonstrated varying turbidity and precipitation stability during storage. Entire NaCas was observed to have adsorbed on S2 zein nanoparticles, corresponding to bigger particles, higher turbidity and lower stability of dispersions than those of S4 and S5. Conversely, only κ-casein was on zein nanoparticles of S4 and S5, corresponding to a higher zein:casein mass ratio and higher surface hydrophobicity than that of S2. The best dispersibility was observed for S4 at pH 7.0 and 0–300 mM NaCl, with the smallest hydrodynamic diameter (∼125 nm), lowest turbidity, and without precipitation during 15-day refrigerated storage. Compositional analyses suggested that κ-casein in S4 was a part of zein nanoparticle matrices and was not detached by increased ionic strength during storage. Conversely, caseins detached from zein nanoparticles of S2 and S5, causing particle aggregation and precipitation. Additionally, the approach in S4 utilized less ethanol (50% v/v vs. 80% in the other two approaches) to dissolve zein. Our work is significant in fabricating delivery systems of bioactive compounds utilizing zein as a carrier biopolymer.

Encapsulation of bioactive compounds in nanoemulsion- based delivery systems

Encapsulation into nanoemulsion-based delivery systems of bioactive compounds characterized by low solubility in aqueous phase, represents an effective approach to improve the dispersion of the bioactives into food products, to protect them against degradation or interaction with other ingredients, to reduce the impact on organoleptic properties of the food and to improve their bioavailability. The aim of the present work is the fabrication of nanoemulsions, based on natural food ingredients, to be used as delivery systems of two different bioactive compounds, resveratrol and curcumin, with the ultimate goal of improving the antioxidant and/or antimicrobial activities of the encapsulated compounds. A preliminary screening study of the optimal emulsion ingredients was carried out through the construction of a pseudo-ternary phase diagram of kinetic stability. The formation of very fine emulsions in the nanometric range (< 200nm) was achieved by high pressure homogenization treatment, choosing those formulations containing small amounts of emulsifier, in order to minimize the impact on the organoleptic properties. Resveratrol (0.01% wt) was encapsulated in peanuts oil-based nanoemulsions, using different emulsifiers, such as soy lecithin and sugar esters. Curcumin was encapsulated in stable solid fat nanoemulsions, using stearic acid as lipid phase, up to 0.1% wt concentration. The nanoemulsions were characterized in terms of physical stability of the mean droplet size (dynamic light scattering) and chemical stability of the encapsulated bioactive compounds (HPLC and UV-Vis spectra analysis) upon accelerated ageing conditions. The effectiveness of the delivery systems was evaluated in terms of antioxidant activity of the encapsulated compounds.

Development and antifungal evaluation of a food-grade U-type microemulsion

Food-grade microemulsions have been of increasing interest to researchers as potential delivery systems for bioactive compounds. However, food-grade microemulsions are difficult to formulate and no microemulsion has been documented for antifungal purpose. The physicochemical characterization of a food-grade glycerol monolaurate (GML)/ethanol (EtOH)/Tween 80/potassium sorbate (PS)/water microemulsion system and the antifungal activities against Aspergillus niger and Penicillium italicum have been studied in this paper. The influence of EtOH and PS on oil solubilization capability was clearly reflected in the phase behaviour of U-type microemulsion systems. One dilution-stable formulation ME (GML/EtOH/Tween 80/PS/water = 3 : 3 : 3.5 : 10.5 : 16) was selected. After 4 days of incubation, ME showed 80%A. niger growth inhibition at 0.2% and 72%P. italicum growth inhibition at 0.1%, respectively, and a delay of conidiation of 2 days compared with the control. In the antifungal activities of the microemulsion, GML and PS made major contributions with similar antifungal activities at a GML/PS weight ratio of 1: 3.5. Food-grade dilution-stable microemulsions prepared with GML as oil phase for antifungal purpose are feasible and solubilization of a hydrotrope contributes to the formation of microemulsions and enhanced antifungal activities. The present report represents the first to develop a food-grade microemulsion system for antifugal purpose.

Application of Supercritical Anti-Solvent Technologies for the Synthesis of Delivery Systems of Bioactive Food Components

To develop edible delivery systems suitable for food applications, regulations require that solvents and ingredients are either generally recognized as safe or listed by the Food and Drug Administration as processing aids. In this work, we studied a food grade polymer-corn zein, a category of alcohol-soluble proteins, as the carrier material for microencapsulating bioactives. Zein is insoluble in aqueous solutions; zein-based delivery systems may thus maintain the integrity in aqueous food products during processing and storage. Three alcohols, i.e., ethanol, methanol, and isopropanol, with an appropriate amount of water were used to dissolve zein. A supercritical anti-solvent process was applied to synthesize micro- and nanoparticles of zein for edible delivery systems of bioactive compounds. We studied critical variables during the particle formation: polymer concentration, CO2 flow rate, and co-solvent chemistry. Particles were produced only when mass transfer was fast enough that the co-solvent in the atomized droplets could be extracted by the reservoir CO2 and polymers could nucleate and grow into particles. Manipulation of the above variables enabled the production of micro- and nanoparticles, which can be used as bases for microencapsulating bioactives. Our results demonstrated promising applications of the supercritical anti-solvent technology to synthesize food grade delivery systems of bioactive food ingredients that can enhance the healthfulness, safety, and quality of food products.

Stimuli-induced Pulsatile or Triggered Release Delivery Systems for Bioactive Compounds

As is frequently found in the living body, many vital functions are regulated by pulsed or triggered release of bioactive substances at a specific site and time. Thus it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems to minimize the undesired side effects. The pulsed or triggered delivery systems are designed to alter their rate of drug delivery in response to stimuli such as changes in a specific molecule, a magnetic or electric field, temperature, light or mechanical forces. Such systems are suitable for the release of therapeutics that benefit from non-constant plasma concentrations. In this article, several types of drug delivery systems which cause the pulsed or triggered release of bioactive compounds due to certain external stimuli, mostly focuses on thermally-, electrically- and magnetically- induced release are described in detail. The recent patents on various delivery systems which release the active compounds only with the external stimuli are described in detail. Keywords: Pulsatile release, triggered release, bioactive compounds, reservoir devices, thermo-responsive, electro-responsive

Time-Controlled Pulsatile Delivery Systems for Bioactive Compounds

In the body under physiological conditions, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific time and site. Thus, to mimic the function of living systems, it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of a bioactive compound at predetermined time intervals. The ability to deliver bioactive compounds and/or therapeutic agents to a patient in a pulsatile or staggered release profile has been a major goal in drug delivery research over the last two decades. The plasma peak is obtained at an optimal time by timing the drug administration. The number of doses per day can be reduced. Based on the relevance of potential therapeutic applications, a variety of design strategies have been formulated in the pursuit of pulsatile release. Overall, these systems can be categorized into reservoir, capsular and osmotic devices. In this review article, several types of dosage forms, including microparticles, coarse particulates, large solid implants, hydrogels, osmotic pumps and liposomes, for time-controlled pulsatile release are discussed. This review describes the recent patents related to pre-programmed delivery systems, such as systems with eroding, soluble or rupturable barrier coatings, and systems with capsular structures.