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Abstract: Degenerative tendinopathy is a significant health problem, and its incidence increases yearly. This condition causes functional deficits in young and adult patients and sedentary or active individuals, resulting in health, social, and economic consequences. Due to limited blood supply, drug administration is complex for tendon diseases, such as degenerative tendinopathy. Biomaterials, such as hydrogels, have gained significant attention in designing drug delivery systems to treat musculoskeletal pathologies due to their attractive characteristics and the challenges posed by conventional drug delivery routes. This paper provides an overview of tendon pathology and discusses the use of hydrogels as drug carriers and release agents in emerging treatments.
Resumen: La tendinopatía degenerativa es un importante problema de salud, y su incidencia aumenta cada año en todo el mundo. Esta condición genera déficits funcionales en pacientes jóvenes o adultos, así como en personas sedentarias o activas, trayendo consigo repercusiones sanitarias, sociales y económicas. Debido al suministro de sangre limitado, la administración de medicamentos es compleja para las enfermedades de los tendones, como la tendinopatía degenerativa. El uso de biomateriales, como los hidrogeles, ha ganado una atención significativa en el diseño de sistemas de administración de fármacos para tratar patologías musculoesqueléticas debido a sus atractivas características y los desafíos que plantean las rutas convencionales de administración de fármacos. Este documento proporciona una descripción general de la patología del tendón y analiza el uso de hidrogeles como transportadores de fármacos y agentes de liberación en tratamientos emergentes.
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OBJECTIVE Temporal lobe epilepsy is a common neurological disease caused by abnormal syn-chronized discharge in the brain and it is mainly treated through long-term use of anti-epileptic drugs(AEDs).This project is supposed to provide an electro-responsive and brain-targeted drug delivery system(DDS)for on-demand drug release,which could promptly block the transmis-sion of epileptic discharges.METHODS The DDS was fab-ricated by co-polymerization of dopamine and pyrrole,together with conjugation of brain-targeted peptide.A number of characterization including electron microscopy,thermogravimetric analysis,dynamic light scattering and other methods were conducted to evaluate the physio-chemical properties of the nanomaterials.In vitro study based on a home-made electric device and high perfor-mance liquid chromatography was performed to record drug release profiles.Three epileptic models including acute,continuous and spontaneous models were estab-lished for the evaluation of therapeutic efficacy.RESULTS Our polymeric DDS has a nanoscale size(ca.80 nm)and could load AEDs such as phenytoin(drug loading capacity 20.4%).The hybrid nanomaterials can improve the brain delivery efficiency through a combination of receptor-mediated transcytosis and near-infrared-enabled brain transport.In vitro study proved that the DDS could release phenytoin in the electric field in a sensitive(50 μA),quick(30 s)and sustained(>3 times)manner.In vivo study demonstrated excellent anti-epileptic effects in a lower dose(20%).Biosafety study further verified that our strategy has limited damage.CONCLUSION For on-demand seizure control,we have developed a nano-engineered DDS with the capability of electro-responsive drug release and brain-targeted accumula-tion.The DDS could increase the AEDs accumulation at epileptic region and release the AEDs in response to the epileptic discharges.Such strategy could timely inhib-it the epileptic seizure.Our work provides a promising approach to"smart"therapy of epilepsy and sheds light on development of pharmacotherapy of other brain disorders.
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Local anesthetic drugs are commonly used to block the conduction function of patient's nerves temporarily for anesthesia during surgery or to provide targeted analgesia after trauma. Compared with general anesthetics, local anesthetics makes less impact on the physiological status and alleviates pain complications in the presence of clear consciousness. However, its clinical application is still limited by its systemic toxicity, as well as toxicity to nerves and muscles, duration of action and lack of penetration. Nanotechnology can help it penetrate the physiological barrier, prolong the time of nerve block, and reduce toxic side effects. In addition, by building a light-responsive release system, local anesthetics can be released on demand, enhancing drug effectiveness and safety. However, in addition to the problems of poor consistency and high production costs, the system of light response release is still limited in application due to the limitation of the depth of penetration of the tissue. According to the current research progress, this paper briefly introduces and analyzes the main dosage forms, hoping to provide new ideas for the responsive release of local anesthetic drugs.
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Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control, light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.
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Traditional ophthalmic pharmaceutical preparations are mostly eye drops or eye ointments, which have the disadvantages of low efficiency and poor patient compliance in application.Drug-loaded contact lenses can overcome these shortcomings and have attracted much attention.Improving drug loading capacity and enhancing sustained-release performance of drug-loaded contact lenses are the main focus of research and development.In recent years, drug-loaded contact lenses made of molecularly imprinted hydrogel can significantly improve drug loading capacity and sustained-release performance, and have been widely studied.The application status of molecularly imprinted hydrogel drug-loaded contact lenses in the delivery of ophthalmic drugs, as well as the effects of various factors on drug loading capacity and sustained-release performance were reviewed in this article.
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Considering that photodynamic therapy (PDT)-induced oxygen consumption and microvascular damage could exacerbate hypoxia to drive more glycolysis and angiogenesis, a novel approach to potentiate PDT and overcome the resistances of hypoxia is avidly needed. Herein, morpholine-modified PEGylated bilirubin was proposed to co-deliver chlorin e6, a photosensitizer, and diclofenac (Dc). In acidic milieu, the presence of morpholine could enable the nanocarriers to selectively accumulate in tumor cells, while PDT-generated reactive oxidative species (ROS) resulted in the collapse of bilirubin nanoparticles and rapid release of Dc. Combining with Dc showed a higher rate of apoptosis over PDT alone and simultaneously triggered a domino effect, including blocking the activity and expression of lactate dehydrogenase A (LDHA), interfering with lactate secretion, suppressing the activation of various angiogenic factors and thus obviating hypoxia-induced resistance-glycolysis and angiogenesis. In addition, inhibition of hypoxia-inducible factor-1α (HIF-1α) by Dc alleviated hypoxia-induced resistance. This study offered a sequentially responsive platform to achieve sufficient tumor enrichment, on-demand drug release and superior anti-tumor outcomes in vitro and in vivo.
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A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pH-triggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOXADH and D-DOXcar con-jugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOXADH(D-DOXADH-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.
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The non-specific accumulation and release of drugs are the main factors affecting the therapeutic effect as well as causing toxic side effects of chemotherapeutic drugs. Nowadays, the application of nanotechnology and responsive drug release is an important strategy to improve the tumor-specific accumulation of drugs and reduce their side effects. In this study, an α-enolase targeted peptide (ETP)-modified polyethylene glycol poly-lysine block copolymer loaded with oxaliplatin prodrug was synthesized first, and then, polymer-coating Fe3O4 nanoparticles were prepared by phase transfer dialysis method to improve the blood circulation stability and tumor targeting of oxaliplatin. At the same time, the physicochemical properties, reductant-responsive drug release, cellular uptake, tumor targeting and other biological functions of ETP modified oxaliplatin-loaded Fe3O4 nanoparticles were studied in vitro and in vivo. First, the results of reductant-triggered drug release study showed that the drug-loaded nanoparticles could achieve rapid release of more than 80% of the prototype oxaliplatin within 3 h under the reduction conditions simulating the tumor cytoplasmic microenvironment. Secondly, the results of flow cytometry showed that the modification of ETP could increase the ratio of cellular uptake of drug-loaded nanoparticles in tumor cells, and the way that drug-loaded nanoparticles endocytosed by tumor cells were mainly through the energy-dependent and receptor protein and fossin-mediated endocytosis pathway. The animal procedures were approved by the Institutional Animal Care and Use Committee of School of Pharmacy of Fudan University. Moreover, the results of pharmacokinetic experiment showed that the area under the curve (AUC0-∞) of oxaliplatin could be significantly increased by nano-formulation which was about 5 times than that of free oxaliplatin. Besides, the pharmacokinetic results also showed that the drug-loaded Fe3O4 nanoparticles constructed by covalent linkage and chelation had good overall stability in vivo. Finally, the in vivo imaging results showed that ETP modification could increase tumor accumulation of drug-loaded nanoparticles, which would be conducive to the efficacy of oxaliplatin in tumor lesions. In summary, the oxaliplatin-loaded Fe3O4 nanoparticles with the capability of reductant-responsive drug release have good drug release characteristics, blood circulation stability and tumor targeting ability, and have the potential to improve the anti-tumor therapeutic effect of oxaliplatin.
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Conventional eye treatment formulation such as eye drops has shortcomings including low drug utilization and poor patient compliance. The contact lens(CL), well-known as visual correction lens, is considered to be a more promising ophthalmic drug delivery vehicle owing to its good biocompatibility, long-term wearing comfort, prolonged drug residence time and improved bioavailability. In order to improve the drug loading efficiency and prolong the release time, researchers have developed a variety of strategies to modify traditional CL, including the introduction of vitamin E molecular barrier, application of molecular imprinting technology of CL, increasing interactions between the drug and polymer matrix by introducing special genes, and incorporation of nanocarriers or drug-loaded polymer films. In this paper, the preparation methods and pros and cons of drug-loaded CL are reviewed. At last, the existing problems and future developments of CL as ophthalmic drug delivery carrier are briefly discussed.
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Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.
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Animals , Male , Female , Mice , Quality Control , Tablets/classification , Drug Interactions , Metoprolol/analysis , In Vitro Techniques/methods , Pharmaceutical Preparations/analysis , Total Quality Management/statistics & numerical dataABSTRACT
Abstract The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr's index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs' gastrointestinal toxicity upon oral administration of ramipril.
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In this study, a dichloromethane fraction dry extract from the underground parts of Jatropha isabellei (DFJi) was used to prepare lipid nanocarriers (LNCJi) aimed at providing the oral delivery of terpenic compounds in the treatment of arthritis. The lipid nanocarriers were prepared by the spontaneous emulsification method. The lipid nanocarriers displayed sizes ranging from 180 to 200 nm and zeta potential values of around -18 mV. A high value of entrapment efficiency (> 90%) was obtained for jatrophone, which was used as the chemical marker of DFJi. LNCJi stored at 4°C were demonstrated to be stable through measurements of transmitted light after analytical centrifugation of the samples. In vitro drug release studies conducted in biorelevant dissolution media demonstrated that jatrophone release was faster from LNCJi than from free DFJi. When tested in an acute arthritis model, the LNCJi exhibited antinociceptive properties after oral administration of a 50 mg/kg dose, unlike the free DFJi, although no reduction in articular diameter was observed. These results suggest that an increase in the oral absorption of DFJi constituents may have occurred through the carrying of this fraction in LNCJi, thus improving the antinociceptive activity of this compound
Subject(s)
Animals , Male , Rats , Arthritis/pathology , In Vitro Techniques/methods , Administration, Oral , Jatropha/adverse effects , Efficiency/classification , Dissolution , Drug Liberation , Lipids/pharmacology , Methylene Chloride/pharmacologyABSTRACT
BACKGROUND: Natural flavonoid formononetin (FN) is traditional Chinese medicine extract and has anticancer effect, but the hydrophobic structure and short half-life in vivo limit their clinical applications. OBJECTIVE: To prepare FN loaded pluronic (PF)-folic acid (FA) conjugated micelles (FN-PF-FA) and to test in vitro drug release and anticancer activity. METHODS: FA coupling PF was prepared by carbodiimide crosslinker chemical method. FN-PF-FA micelles were prepared by film hydration method. The encapsulation efficiency, drug loading and drug release performance of FN-PF and FN-PF-FA micelles were measured. The in vitro anti-cancer activity of flavin, FN-PF micelles, and FN-PF-FA micelles on folic acid-overexpressing human liver cancer HepG2 cells was measured by in vitro thiohodamine B experiment. RESULTS AND CONCLUSION: (1) The encapsulation efficiency of FN-PF and FN-PF-FA micelles was (84.12±2.15)% and (82.50±1.78)%, respectively, and the drug loading was (21.33±2.27)% and (19.73±1.58)%, respectively. (2) The release rate of both micelles in acidic environment was faster than that in alkaline environment. In the same condition, the release rate of FN-PF-FA micelles was slower than that of FN-PF micelles. (3) At the same drug concentration, the ability of FN-PF micelles and FN-PF-FA micelles to inhibit the proliferation of human liver cancer HepG2 cells was stronger than that of free FN (P < 0.05). Moreover, the inhibitory effect of FN-PF-FA micelles was stronger than that of FN-PF micelles (P < 0.05). (4) The order of drug concentration required to inhibit tumors was FN-PF-FA < FN-PF < free FN, and there was a significant difference between groups (P < 0.01). (5) Results suggested that FN-PF-FA micelles had the potential to target the release of anticancer drugs.
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OBJECTIVE@#Traditional Chinese medicine (TCM) has been widely used throughout China to prevent and cure diseases for thousands of years, and now it is a part of the integrative medicine field that is available in Western societies. To ensure the safety and quality of the herbal medicines that are a major part of the TCM tradition, they must be held to modern pharmaceutical standards. Erzhi pill (EZP) is a Chinese Pharmacopeia-listed herbal preparation that is used in the long-term clinical management of post-menopausal symptoms, osteoporosis and menstrual disorders. Until now, whether the drug release mechanism of EZP is in line with its intended TCM usage has not been studied.@*METHODS@#The release of specnuezhenide from three EZPs (self-made, Leiyunshang and Renhe) in simulated gastric fluid (SGF), acetate buffer (pH 4.5 buffer) and simulated intestinal fluid (SIF) was investigated in a dissolution test. The water uptake capacity and erosion extent of the three EZPs were investigated using swelling and erosion studies. The drug release mechanism was further assessed through statistical model fitting, using DDSolver software.@*RESULTS@#The release of specnuezhenide from all three EZPs in SGF was less than 50% within a 4 h period. However, over 70% of the specnuezhenide was released from each EZP in both pH 4.5 buffer and SIF in the same time. Analysis of the swelling and erosion behaviors and the drug release mechanism of the three EZPs confirmed that the release rate from EZP followed a sustained release profile, which was an interactive combination of swelling and erosion.@*CONCLUSION@#This study showed that the release pattern from the pills was in line with the intended TCM use of EZP. TCM had not only theoretically considered sustained release from the pills, but also formulated them to achieve this release pattern. When establishing quality control standards for pills, the theoretical TCM usage and the actual release patterns need to be considered.
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Salidroside (SAL) is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at K
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Tumor microenvironment has been widely utilized for advanced drug delivery in recent years, among which hypoxia-responsive drug delivery systems have become the research hotspot. Although hypoxia-responsive micelles or polymersomes have been successfully developed, a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear. Herein, we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based (
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OBJECTIVE:To preparea novel Curcumin (Cur)dry powder inhalation (DPI)loaded by nanoporous flower-shaped lactose(FL),and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs. METHODS :FL-loaded Cur (Cur-FL) compound powder was prepared by solution adsorption method. Using drug-loading amount and adsorption rate as indicators ,single-factor experiment was used to optimize Cur concentration,Cur-FL ratio (m/m)and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder. Fourier transform infrared spectroscopy ,scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology. The water content and aerodynamic properties were determined ;in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid. RESULTS :The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL,Cur-FL ratio of 1 ∶ 4,adsorption time of 1 h. The drug-loading amount of compound powder was (23.37±0.43)%,the encapsulation rate was (91.64±0.44)%,and the adsorption rate was (30.50±0.72)%. Cur-FL particles were flower shaped ;Cur was physically adsorbed in the pores of FL without chemical changes. The bulk density of Cur-FL compound was (0.21±0.02) g/cm3,tap density was (0.33±0.01)g/cm3,angle of repose was(24.07±0.31)°,average particle size was (3.96±0.80) μm,aerodynamic particle size was (3.33±0.99)μm,water content was (5.63 ±0.24)%,emptying rate was (92.53± 0.87)%,and deposition rate of effective parts in vitro was son- (45.93 ± 1.77)% . Its 24 h solubility in artificial lung gwen.tan@csu.edu.cn fluid [(358.93±1.67)μg/mL] were 3.28 times of Cur ,48 h cumulative release ratesin in vitro (90.21%)were 1.63 times of Cur ,but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid. CONCLUSIONS :Cur-FL compound powder has good in vitro release property ,and its powder properties ,solubility,water content ,fluidity and aerodynamic properties meet the requirements of DPI in Chinese Pharmacopoeia.
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OBJECTIVE:To prepare Liguatrazine opthalmic liposome therm osensitive gel ,and to investigate its in vivo and in vitro characteristics. METHODS :The ammonium sulfate gradient method was used to prepare Liguatrazine liposomes. The preparation technology was optimized by using orthogonal test. Using poloxamer P 407 as gel matrix ,Liguatrazine liposomes were prepared into thermosensitive gel. A membraneless model was used to study the dissolution and in vitro drug release of the gel. The modified Franz diffusion cell was used to investigate corneal permeability and further determine corneal hydration value. The effects of the gel on the proliferation of human corneal epithelial cell HCE-T. HE staining and Draize test were used to investigate the stimulatory effects of the gel on corneal cells of the rabbit ,and the histological changes of the eyes were observed. RESULTS :The optimal preparation technology of Liguatrazine liposome was drug-lipid ratio of 1 ∶ 10(m/m),the ammonium sulfate concentration of 0.2 mol/L,phospholipid-cholesterol ratio of 4∶1(m/m),incubation temperature of 45 ℃. Then ligustrazine opthalmic liposome thermosensitive gel was prepared with 23% poloxamer P 407 as gel matrix. The gel had good gelatinization temperature. The in vitro drug release and dissolution showed zero-order kinetic characteristics ,and in vitro drug release of the gel was mainly related to dissolution (R2=0.993 4). The cumulative transcorneal permeability of the gel was 43.3% within 6 hours and corneal hydration value was 72.98%. Low and medium concentrations (1,5 mg/L)of Ligustrazine opthalmic liposome thermosensitive gel had no obvious proliferation toxicity to HCE-T cells ,but it showed cytotoxicity at high concentration (10 mg/L). The mean Draize eyeirritation score of the gel on rabbit cornea was within non-stimulation,and there was no abnormal change in rabbit (No.2018001) corneal histology. CONCLUSIONS : Prepared Ligustrazine opthalmic liposome thermosensitive gel has a suitable phase transition temperature ,good corneal permeability ,and low corneal irrit ation.
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Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.
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Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.