Triggered Drug Release Research Articles

ATP-Triggered Drug Release of Self-Assembled 3D DNA Nanostructures for Fluorescence Imaging and Tumor Therapy.

Stimulus-responsive materials are ideal carriers for precisely controlled drug delivery due to their high selectivity. However, the complex physiological environment hinders its development in clinical medicine. Here, we aim to design a self-assembled three-dimensional (3D) DNA nanostructure drug delivery system with adenosine-5'-triphosphate (ATP)-triggered drug release for tumor fluorescence imaging analysis and targeted drug delivery. Dox@3D DNA nanostructures are self-assembled by a simple one-pot annealing reaction and embedded with drugs, which are structurally stable but can be induced using high concentrations of ATP in tumor cells to cleave and release drugs rapidly, facilitating the rapid accumulation of drugs in tumors and exerting therapeutic effects, thus effectively avoiding damage to normal tissues. This work demonstrates that 3D DNA nanostructures can be used as efficient drug nanocarriers with promising applications in tumor therapy.

Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms.

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10–20 wt %), drug load (30–50 wt %), and duration of AMF (3–15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.

Design and fabrication of chitosan-based AIE active micelles for bioimaging and intelligent delivery of paclitaxel

In this study, cetyl 4-formylbenzoate alkyl and 4-(2-hydroxyethoxy) benzophenonesalicylaldazide modified biotinylated chitosan (CS-BT-HBS-CB) featured with aggregation-induced emission (AIE) characteristic, active tumor-targeting ability and pH-responsive drug release property was designed and synthesized. The polymer was fabricated by introducing hydrophobic segment, tumor targeting ligand, acid-sensitive bond and AIE fluorophore to the backbone of chitosan. Due to its amphiphilicity, the polymer could self-assemble into micelles and encapsulate paclitaxel (PTX) to form PTX-loaded CS-BT-HBS-CB micelles. The mean size of the micelles was 167 nm, which was beneficial to the EPR effect. Moreover, with the help of above functional groups, the micelles exhibited excellent AIE effect, triggered drug release behavior by acidic condition, selective internalization by MCF-7 cells and excellent cellular imaging capability. In vivo studies revealed that the PTX-loaded CS-BT-HBS-CB micelles could enhance the antitumor efficacy with low systemic toxicity. This micellar system would be a potential candidate for cancer therapy and bioimaging.

Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles

Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

Photo-Induced Drug Release from Polymeric Micelles and Liposomes: Phototriggering Mechanisms in Drug Delivery Systems.

Chemotherapeutic drugs are highly effective in treating cancer. However, the side effects associated with this treatment lower the quality of life of cancer patients. Smart nanocarriers are able to encapsulate these drugs to deliver them to tumors while reducing their contact with the healthy cells and the subsequent side effects. Upon reaching their target, the release of the encapsulated drugs should be carefully controlled to achieve therapeutic levels at the required time. Light is one of the promising triggering mechanisms used as external stimuli to trigger drug release from the light-responsive nanocarriers. Photo-induced drug release can be achieved at a wide range of wavelengths: UV, visible, and NIR depending on many factors. In this review, photo-induced release mechanisms were summarized, focusing on liposomes and micelles. In general, light-triggering mechanisms are based on one of the following: changing the hydrophobicity of a nanocarrier constituent(s) to make it more soluble, introducing local defects within a nanocarrier (by conformational transformation or photo-cleavage of its lipids/polymers chains) to make it more porous or concentrating heat for thermo-sensitive nanocarriers to release their payload. Several research studies were also presented to explore the potentials and limitations of this promising drug release triggering mechanism.

Light activated pulsatile drug delivery for prolonged peripheral nerve block

Regional anesthesia is widely used in peripheral nerve block and in neuraxial anesthesia to reduce anesthetics systemic side effects and shorten recovery times. However, when applied as a single injection (e.g., peripheral nerve block) it is limited by the duration of its effect. Herein, we develop a thermoresponsive nanogel based on poly(oligoethylene glycol methacrylate) containing the long-lasting anesthetic bupivacaine, which can be externally activated by using near-infrared light due to the photothermal properties of hollow gold nanoparticles embedded in the nanogel which facilitate its phase transition, triggering drug release at a controlled temperature above body temperature. Bupivacaine in vitro release can be repeatedly triggered to achieve a controlled pulsatile release of the drug due to the reversible nature of the thermosensitive nanogel, achieving a spatio-temporal control of the release. In vivo sciatic nerve block demonstrates that whereas the administered dose of free bupivacaine produces sensory block and impaired motor function for 2 h, the equivalent bupivacaine dose included in the developed release system can significantly prolong its neurobehavioral anesthetic effect for over 6 h. This release system can also be reactivated multiple times by subsequent irradiation cycles without observing detrimental toxicity in the infiltrated tissues.

Dendritic polyurethane-based prodrug as unimolecular micelles for precise ultrasound-activated localized drug delivery

Ultrasound has been recognized as an exciting tool to enhance the therapeutic efficacy in tumor chemotherapy owing to the triggered drug release, facilitated intracellular drug delivery, and improved spatial precision. Aiming for a precise localized drug delivery, novel dendritic polyurethane-based prodrug (DOX-DPU-PEG) was fabricated with a drug content of 18.9% here by conjugating DOX onto the end groups of the functionalized dendritic polyurethane via acid-labile imine bonds. It could easily form unimolecular micelles around 38 nm. Compared with the non-covalently drug-loaded unimolecular micelles (DOX@Ph-DPU-PEG), they showed excellent pH/ultrasound dual-triggered drug release performance, with drug leakage of only 4% at pH 7.4, but cumulative release of 14% and 88% at pH 5.0 without and with ultrasound, respectively. The ultrasound responsiveness was attributed to the unique strawberry-shaped topological structure of the DOX-DPU-PEG, in which DOX was embedded in the skin layer of the hydrophobic DPU cores. With ultrasound, the DOX-DPU-PEG unimolecular micelles possessed enhanced tumor growth inhibition than free DOX but showed no obvious cytotoxicity on the tumor cells without ultrasound. Such feature makes them promising potential for precise localized drug delivery.

PH-Responsive Nanocarriers in Cancer Therapy.

A number of promising nano-sized particles (nanoparticles) have been developed to conquer the limitations of conventional chemotherapy. One of the most promising methods is stimuli-responsive nanoparticles because they enable the safe delivery of the drugs while controlling their release at the tumor sites. Different intrinsic and extrinsic stimuli can be used to trigger drug release such as temperature, redox, ultrasound, magnetic field, and pH. The intracellular pH of solid tumors is maintained below the extracellular pH. Thus, pH-sensitive nanoparticles are highly efficient in delivering drugs to tumors compared to conventional nanoparticles. This review provides a survey of the different strategies used to develop pH-sensitive nanoparticles used in cancer therapy.

Ultrasound-Mediated Release of Gaseous Signaling Molecules for Biomedical Applications.

Although nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S) have been considered as notorious gas pollutants for decades, they are considered as endogenous gaseous signaling molecules (GSMs), which have been widely recognized for their important signaling functions and prominent medical applications in human physiology. To achieve local delivery of GSMs to optimize therapeutic efficacy and reduce systemic side effects, stimuli-responsive nanocarriers have been successfully developed. Among them, ultrasound is considered as an attractive theranostic modality that can be used to track drug carriers, trigger drug release, and improve drug deposition, etc. In this minireview, recent achievements in designing ultrasound-responsive nanocarriers for the controlled delivery of GSMs and their biomedical applications are summarized. This emerging research direction enables the controlled delivery of GSMs to deep tissues, and the combination of ultrasound imaging techniques offers many possibilities for the fabrication of new theranostic platforms.

Sonochemical fabrication of reduction-responsive alginate-based nanocapsules with folate targeting for drug delivery

Smart drug delivery systems for anti-cancer treatment applications have been attractive gradually. Development of suitable smart drug carriers with targeted drug delivery capability and stimuli-responsive drug release ability is of crucial importance for accurate transport anti-cancer drugs to tumor cells and their efficient release. In the study, the biocompatible folate-modified reductive-responsive alginate-based nanocapsules (FA-RANCs) was developed using FA decorated thiolated alginate via sonochemical method for targeted delivery and controlled release of hydrophobic drugs. The wall of FA-RANCs was constructed by disulfide bonds formed from hydrosulfuryl groups and the hydrophobic drug dispersed in the oil phase to be encapsulated into nanocapsules. The FA-RANCs were endowed with folate targeting function owing to the grafting of folic acid on the surface of the capsules and FA-RANCs could be taken into Hela cells via folate-receptor (FR)-mediated endocytosis effect. Moreover, the FA-RANCs showed excellent reduction-responsive release property for hydrophobic anti-cancer drugs on account of the disulfide bonds in the shell of nanocapsules. According to the above results, FA-RANCs would be a promising controllable drug delivery system for targeted delivery and triggered release of hydrophobic drugs in biomedical area.

Aptamerized silica/gold nanocapsules for stimulated release of doxorubicin through remote two-photon excitation

ABSTRACT Precision-based drug delivery via remote triggering is fast becoming an attractive therapeutic design and is highly useful in complicated clinical situations that may require accurate site-delivery of drug while reducing the risk of collateral damage to surrounding healthy tissue. Of the many strategies available to achieve these desirable effects, silica/gold nano-assemblies offers a practical means to achieving these aims. Herein, as a proof-of-concept, a silica nanocapsule passivated with a gold outer nanoshell had been fabricated to deliver Doxorubicin, and this nano-assembly can be remotely triggered via two-photon excitation (TPE), even under in vivo setting. A polyethylene glycol (PEG) layer as well as AS1411 DNA aptamer had also been grafted to the surface to improve homing specificity toward MDA-MB-231 breast cancer tissue. The assembly of silica/gold nanocapsules was characterized via TEM, FTIR, and UV-Vis to validate the the nanoconstruct. Upon TPE irradiation, a higher expression level of Annexin V and Caspase-3 was observed in both in vitro and in vivo animal models. A significant reduction in tumor size on mice model was noticed after 21 days, and these results had suggested a viable nano-sized design serving as remotely triggered drug release platform based on current well-established silica nanoparticulate methodologies.

Optical Characterization of Cobalt Ferrite and Magnetoelectric Cobalt Ferrite-Barium Titanate Core Shell Nanoparticles in Infra-Red Range

Cobalt Ferrite- Barium Titanate core-shell nanoparticle has shown application in targeted drug delivery via an external magnetic field. This paper focuses on the absorption peak in the Infrared region of the aforementioned core-shell nanoparticles that can allow scope for application in photo simulation or triggering drug release at a specific absorption band. FTIR was used to verify the absorption peak for 50 nm Cobalt Ferrite nanoparticles, Cobalt Ferrite- Barium Titanate core-shell nanoparticles of 50<b>- 50</b> composition, and Barium Titanate. The absorption peak was obtained at 2893 nm, 2850 nm, and 2930 nm respectively. The shift was due to the inherent chemical bonds and dielectric properties. The results for absorption peak were verified with Finite Element Analysis using a simulation tool, COMSOL. The results followed a general trend and the absorption peaks were at 2150 nm, 2350 nm, and 2400 nm respectively. Also, the shift in resonance peak for cobalt ferrite and its core-shell with barium titanate was compared with the cavity perturbation technique in the microwave frequency range. It was realized that the shift in resonance mode, quality factor, and loss tangent was slightly higher for core-shell due to the damping effect induced by the difference in optical and dielectric properties.

Drug Release from Gelsolin-Targeted Phase-Transition Nanoparticles Triggered by Low-Intensity Focused Ultrasound.

PurposeCurrent strategies for tumour-induced sentinel lymph node detection and metastasis therapy have limitations. It is essential to identify and provide warnings earlier for tumour metastasis to carry out effective clinical interventions. In addition, traditional cancer chemotherapy encounters drastic limitations due to the nonspecific delivery of antitumour drugs and severe side effects. We aimed to exploit the potential of gelsolin (GSN) monoclonal antibody as a targeting agent and perfluorohexane (PFH) as a phase-transition agent to maximize the cytotoxic effect of poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug controllable release systems for Hca-F cells.MethodsWe co-encapsulated PFH and doxorubicin (DOX) into PLGA nanoparticles (NPs) and further conjugated GSN monoclonal antibody onto the surface of NPs to form GSN-targeted phase transition polymer NPs (GSN-PLGA-PFH-DOX) for both imaging and therapy of tumours and metastatic lymph nodes. To promote and trigger drug release on demand, low-intensity focused ultrasound (LIFU) was applied to achieve a controllable release of the encapsulated drug.ResultsGSN-PLGA-PFH-DOX NPs exhibited characteristics such as a narrow size distribution and smooth surface. GSN-PLGA-PFH-DOX NPs could also specifically bind to Hca-F cells and increase the ultrasound contrast agent (UCA) image contrast intensity. GSN-PLGA-PFH-DOX NPs enable GSN-mediated targeting and biotherapeutic effects as well as LIFU-responsive drug release, resulting in synergistic cytotoxic effects in GSN-overexpressing cells in vitro.ConclusionOur work might provide a strategy for the imaging and chemotherapy of primary tumours and their metastases.

Permeability of the Composite Magnetic Microcapsules Triggered by a Non-Heating Low-Frequency Magnetic Field.

Nanosystems for targeted delivery and remote-controlled release of therapeutic agents has become a top priority in pharmaceutical science and drug development in recent decades. Application of a low frequency magnetic field (LFMF) as an external stimulus opens up opportunities to trigger release of the encapsulated bioactive substances with high locality and penetration ability without heating of biological tissue in vivo. Therefore, the development of novel microencapsulated drug formulations sensitive to LFMF is of paramount importance. Here, we report the result of LFMF-triggered release of the fluorescently labeled dextran from polyelectrolyte microcapsules modified with magnetic iron oxide nanoparticles. Polyelectrolyte microcapsules were obtained by a method of sequential deposition of oppositely charged poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the surface of colloidal vaterite particles. The synthesized single domain maghemite nanoparticles integrated into the polymer multilayers serve as magneto-mechanical actuators. We report the first systematic study of the effect of magnetic field with different frequencies on the permeability of the microcapsules. The in situ measurements of the optical density curves upon the 100 mT LFMF treatment were carried out for a range of frequencies from 30 to 150 Hz. Such fields do not cause any considerable heating of the magnetic nanoparticles but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations of the adjacent materials. We observed the changes in release of the encapsulated TRITC-dextran molecules from the PAH/PSS microcapsules upon application of the 50 Hz alternating magnetic field. The obtained results open new horizons for the design of polymer systems for triggered drug release without dangerous heating and overheating of tissues.

Triggering Drug Release and Thermal-Disrupting Interface Induced Mitigation of Composite Photothermal Hydrogel Treating Infectious Wounds.

Introduction: With the development of photothermal technology, the appearance of composite photothermal hydrogels has increased the selectivity of treating infectious skin defects. However, how to design composite photothermal hydrogel with better antibacterial performance, reduce the resistance rate of bacteria, and the damage rate of normal tissue still needs further study. Methods: The Prussian blue and tannic acid were loaded on polyacrylamide hydrogels. Characterization of DLS, Zeta potential, UV absorption spectrum, hydrogel swelling rate, scanning electronic microscopic, drug release profile, photothermal properties, in vitro cytocompatibility, and antibacterial properties. Experiments were measured by skin defect repair, antibacterial detection, and histological staining experiments. Results: The polyacrylamide hydrogel with photothermal effect and controllable release of tannic acid was successfully prepared. The hydrogel has strong light transmittance and adhesion, and the swelling rate can reach 600%, which improves the self-cleaning ability. SEM results showed the porous structure of hydrogels, promoting cell growth. Through photothermal switches, the composite hydrogel represented adjustable and controllable drug release ability. Combined with the synergistic antibacterial effect of tannic acid, this further enhanced the antibacterial ability and reduced the probability of antibiotic resistance. The in vitro and in vivo experiments showed the hydrogel had good biocompatibility and excellent antibacterial properties, which could promote the repair of infectious skin defects in SD rats. Conclusion: We fabricated a hydrogel with a triggering drug release rate, alleviating heat damage, transparent morphology, mechanical stability, strong adhesion, good biocompatibility, and synergistic antibacterial ability, which presents new treatment options for infectious skin defect repair.

Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis

Formulation design for colon-specific delivery of 5-aminosalicylic acid (5-ASA) could bring some therapeutic benefits in the treatment of ulcerative colitis (UC).In the current study, a 32 full factorial design was used to predict optimum coating composed of two enteric (poly methacrylic acid, methyl methacrylates 1:2 and 1:1) and time-dependent (poly ethyl acrylate, methyl methacrylate, trimethylammonio ethyl methacrylate chloride 1:2:0.1) polymethacrylates for colon-specific delivery of 5-ASA pellets. A unique coating composition and coating level predicted by the model was applied onto either inulin-free 5-ASA pellets or inulin-bearing 5-ASA pellets and the coated pellets were examined by dissolution test in-vitro. The coated pellets were also tested in a rat model of UC and compared with the a commercially available colonic delivery system of 5-ASA.The ratio of the two enteric polymethacrylates and time-dependet polymethacrylate of 16:64:20 w/w at a coating level of 15% was discovered as the optimum coating for delivery of 5-ASA pellets to the colon. In general, the coated pellets offered a better therapeutic outcome compared to commercially available colonic delivery system of 5-ASA and uncoated pellets in terms of colitis activity index and the colon's tissue enzymes of MDA and GSH.It seems that the coating composed of enteric and pH-dependent polymethacrylates could tune up the rate of drug release from 5-ASA-coated pellets and trigger drug release based on pH and time.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy.

Simple SummaryMild hyperthermia is a technique that induces a local tumor temperature increase up to 43.0 °C. In this paper, we introduce three devices that could be used to apply hyperthermia in small animals in combination with intravital microscopy for the real-time visualization of in vivo intratumoral events such as drug delivery.This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.

PH and reduction dual-responsive feather keratin - sodium alginate nanogels with high drug loading capacity for tumor-targeting DOX delivery

As a natural polymer, there are a lot of functional groups on the keratin molecular chains, such as carboxyl, amino and hydroxyl groups. In the present study, we used keratin (K) as a multifunctional crosslinker and prepared smart nanogels. The nanogels had high loading capacity for drug, while low drug leakage. The surface of the DOX@K/SA-NG is negatively charged and the size was determined to be 432 nm. The nanogels had drug loading capacity (DLC) of 65.2% (w/w) and were capable of triggering drug release upon both pH and reductive (glutathione (GSH)) environment while stable under physiological conditions (pH 7.4 + 10 μM GSH). We evaluated its cancer treatment performance through cell uptake and cytotoxicity experiments, it showed that the prepared DOX@K/SA-NG can effectively inhibit the growth of HepG2 cancer cells.

Self-assembled magnetic polymeric micelles for delivery of quercetin: Toxicity evaluation on isolated rat liver mitochondria

Multifunctional nanocarriers as a promising platform could provide numerous opportunities in the field of drug delivery. Drug carriers loaded with both magnetic nanoparticles (MNPs) and therapeutic agents would allow the combination of chemotherapy with the possibility of monitoring or controlling the distribution of the nano vehicles in the body which may improve the effectiveness of the therapy. Furthermore, by applying these strategies, triggering drug release and/or synergistic hyperthermia treatment are also reachable. This study aimed to explore the potential of the quercetin (QUR) loaded magnetic nano-micelles for improving drug bioavailability while reducing the drug adverse effects. The bio-safety of developed QUR loaded magnetic nano-micelles (QMNMs) were conducted via mitochondrial toxicity using isolated rat liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric reducing ability of plasma (FRAP). QMNMs with a mean particle size of 85 nm (PDI value of 0.269) and great physical stability were produced. Also, TEM images indicated that the prepared QMNMs were semi-spherical in shape. These findings also showed that the constructed QMNMs, as a pH-sensitive drug delivery system, exhibited a stable and high rate of QUR release under mildly acidic conditions pH (5.3) compared to neutral pH (7.4). The most striking result to emerge from the data is that an investigation of various mitochondrial functional parameters revealed that both QMNMs and QUR have no specific mitochondrial toxicity. Altogether, these results offer overwhelming evidence for the bio-safety of QMNMs and might be used as an effective drug delivery system for targeting and stimuli-responsive QUR delivery.

Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.