Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

Sustained-release drug delivery systems for the treatment of glaucoma

Glaucoma,a leading cause of irreversible blindness,affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection.Although topical therapies are often effective when used as prescribed,the drawbacks of current medical management methods include poor patient adherence,local and systemic side effects,and in some cases,limited therapeutic efficacy.Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration.Several platforms are in various stages of development with promising pre-clinical and clinical data.The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020,making it the first long-term injectable therapy available for the treatment of glaucoma.This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.

Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo , its efficacy in inhibiting BIU 87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU 87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer..

Polymeric Hydrogel Nanocapsules: A Thermo and pH Dual-responsive Carrier for Sustained Drug Release

Hydrogel capsules show attractive prospects in drug delivery recently because of high drug loading and sustained release behavior. In this study we reported a simple and convenient route to fabricate poly(acrylic acid)-poly(N-isopropylacrylamide)(PAA-PNIPAm) hydrogel capsules by using hydroxypropylcellulose-poly(acrylic acid)(HPC-PAA) complexes as the templates. The capsules showed a high drug loading(～280% to the weight of capsules) for Doxorubicin hydrochloride. The release of drug from the capsules was responsive to the temperature and p H of the surroundings, showing a low-rate but sustained release behavior favorable for low-toxic and long-term therapy. Together with the convenient preparation, high drug loading, dual responsivity as well as the sustained release feature, it is implied that this polymeric hydrogel capsule might be a promising candidate for new drug carriers.

Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

The captopril/Chitosan-gelatin net-polymer microspheres(CTP/CGNPMs) were prepared using Chitosan(CTS) and gelatin(GT) by the methods of emulsification,cross-linked reagent alone or in combination and microcrystalline cellulose(MCC) added in the process of preparation of microspheres,which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(CTP). The results indicated that CTP/CGNPMs had a spherical shape,smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio(EMR) and composition of cross linking reagents. Among these factors,the EMR(1/4),CLR(FA+SPP) and 0.75% microcrystalline cellulose(MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER,DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%,9.95±0.77% and 261±42%,respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.

Enhanced delivery efficiency and sustained release of biopharmaceuticals by complexation-based gel encapsulated coated microneedles:rhIFNα-1b example

Coated microneedles(MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs(GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate(SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs(72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs(88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFN α-1 b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFN α-1 b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-1 b in GEC-MNs(4.51 ng/ml ·h) was bioequivalent to the intradermal(ID) injection(5.36 ng/ml ·h) and significantly higher than water-soluble coated MNs(3.12 ng/ml ·h). The rhIFN α-1 b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical.

Preparation and Characterization in vitro of Sustained-release Captopril/ Chitosan-gelatin Net-polymer Microspheres(Cap/CGNPMs)

The captopril/ Chitosan-gelatin net-polymer microspheres （ Gap/ CGNPMs ） were prepared using Chitosan （ CS ） and gelatin （ Gel ） by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose （ MCC ） was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvemeat of the therapeutic efficiency and the decrease of the side effects of captopril （ Cap ）. The results indicate that Cap/ CGNPMs have a spherical shape , smooth surface roorphology and integral inside structure and no adhesive phenomena and good roobility , and the size distribution is mairdy from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/ CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets （COT）, embedding ratio （ER） , drug loading （ DL ）, and swelling ratio （ SR ）, and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio （EMR） , composition of cross linking reagents. Among these factors , the EMR（1/4）, CLR （ FOR ＋ TPP） and 0.75% microcrystulline cellulose （MCC） added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsifieation and crossinking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

Effect of rhBMP-2 sustained-release nanocapsules on the ectopic osteogenesis process in Sprague-Dawley rats

Objective:To explore the effect of sustained-release recombinant human bone morphogenetic protein-2(rhBMP-2) on ectopic osteogenesis in the muscle pouches of rats through preparing rhBMP-2 sustained-release capsules by wrapping morphogenesis protein bones-2(BMP-2)using chitosan nanoparticles,and compositing collagen materials.Methods:Twenty four SpragueDawley rats were randomly divided into four groups with six rats in each group,that is Group A(control group),Group B(only treated with collagen),Group C(rhBMP-2+collagen treated group) and Group D(rhBMP-2/cs+collagen treated group).The composite materials for each group were implanted in the bilateral peroneal muscle pouches in rats.The peroneal muscles were only separated without implanting any materials in control group.Rats were sacrificed 2 weeks and 4 weeks post treatment and samples were cut off for general observation,Micro CT scans and histological observation.Results:General observation showed no new bone formation in Groups A and B mice,while new bones were formed in Groups C and D mice.Two weeks after treatment Micro CT scans showed that The bone volume fraction(BVF),trabecular thickness(Tb. Th),bone mineral density(BMD) in Group C mice were all higher than that in Group D(P<0.05). At the fourth week,the BVK,Tb.Th and BMD were significantly higher than that at the second week(P<0.01).Conclusions:The slow-release effect of rhBMP-2/cs sustained-release capsules can significantly promote ectopic osteogenesis.Its bone formation effect is better than that of rhBMP-2 burst-release group.

Alginate encapsulated mesoporous silica nanospheres as a sustained drug delivery system for the poorly water-soluble drug indomethacin

We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.

Incorporation of Carvedilol into PAMAM-functionalized MWNTs as a sustained drug delivery system for enhanced dissolution and drug-loading capacity

The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.

Yeast-Controlled Double-Shelled CacO_(3)/CaF_(2)Hollow Nanospheres with Hierarchically Porous for Sustained pH-Sensitive Drug Release

Hierarchically porous materials(HP materials)are believed one of the most hopeful matrix materials because of their distinctive multimodal pore structures and tremendous application potentials in the field of biomedicine.However,green and facile synthesis of hierarchically porous nanomaterials with beneficial water dispersibility and biocompatibility is still a great challenge.Herein,a novel biomimetic strategy is proposed to prepare the cell-tailored double-shelled HPCaCO_(3)/CaF_(2) hollow nanospheres under the mediation of yeast cells.The biomolecules derived from the secretion of yeast cells are used as conditioning and stabilizing agents to control the biosynthesis of the HPCaCO_(3)/CaF_(2) materials,which exhibit excellent water dispersibility and favorable biocompatibility.The double-shelled CaCO_(3)/CaF_(2) nanospheres hold hierarchically porous structure and have abundant pore channel and large specific surface area,showing high drug-loading and a prolonged drug sustainable release profile by the pore-by-pore diffusion pattern of the hierarchical pores.Otherwise,the HPCaCO_(3) with pH-sensitivity could controllably release drug doxorubicin hydrochloride(DOX)at the acidic tumor microenvironment.Both in vitro and in vivo results demonstrate that HPCaCO_(3)/CaF_(2) has the sustainable pH-sensitive drug release property,showing an enhanced therapeutic effect.Summarily,this study provides a biomimetic strategy to synthesize the hierarchically porous double-shelled hollow nanomaterials for applying in sustainable drug delivery system.

PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers:Preparation,Characterization and Release in vitro

To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

Molecularly imprinted nanoparticles and their releasing properties, bio-distribution as drug carriers

Molecular imprinted nanoparticles(MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine(VBL) as a model drug, and investigated the drug loading,releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm,had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs(MINPs-VBL) were 83.25% and 8.72% respectively. In PBS(pH 7.4),MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPsVBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection(VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index(DTI) and drug selecting index(DSI).

Development and evaluation of Panax notoginseng saponins contained in an in situ pHtriggered gelling system for sustained ocular posterior segment drug delivery

Objective:This study aimed to lay the foundation for the research on Panax notoginseng saponins(PNS)in pH-sensitive in situ gel and the development and improvement of related preparations.Methods:We used Carbopol■940,a commonly used pH-sensitive polymer,and the thickener hydroxypropyl methylcellulose(HPMC E4M)as an ophthalmic gel matrix to prepare an ophthalmic in situ gel of PNS.In addition,formula optimization was performed by assessing gelling capability with the results of in vitro release studies.In vitro(corneal permeation,rheological,and stability)and in vivo(ocular irritation and preliminary pharmacokinetics in the vitreous)studies were also performed.Results:The results demonstrated that the in situ gelling systems containing PNS showed a sustained release of the drug,making it an ideal ocular delivery system for improving posterior ocular bioavailability.Conclusions:This study lays the foundation for the research of PNS contained in an in situ pH-triggered gel as well as the development and improvement of related preparations.It concurrently traditional Chinese medicine with a contemporary in situ gelling approach to provide new directions for the treatment of posterior ocular diseases such as diabetic retinopathy.

Current sustained delivery strategies for the design of local neurotrophic factors in treatment of neurological disorders

Although therapeutic potential of neurotrophic factors(NTFs)has been well recognized for over two decades,attempts to translate that potential to the clinic have been disappointing,largely due to significant obstacles in delivery,including inadequate protein dose/kinetics released at target sites.Considerable efforts have been made to improve the therapeutic performance of NTFs.This articles reviews recent developments in localized delivery systems of NTFs for the neurological disorders treatments with a main focus on sustained delivery strategies.Different non-covalent binding approaches have been employed to immobilize proteins in hydrogels,microspheres,electrospun nanofibers,and their combined systems,which serve as depots for sustained local release of NTFs.The challenges associated with current NTFs delivery systems and how these systems can be applied to neurological diseases and disorders have been discussed in the review.In conclusion,optimal delivery systems for NTFs will be needed for reliable and meaningful clinical benefits;ideally,delivering a time and dose-controlled release of bioactive multiNTFs at different individual optimal kinetics to achieve multi-functions in target tissues is significant preferred.

低临界胶束浓度PEGMA-b-PCL的制备及其药物缓释性能

以ε-己内酯(ε-CL)为疏水链段、聚乙二醇甲醚甲基丙烯酸酯(PEGMA)为亲水链段、4-氰基-4-[(十二烷基硫烷基硫代羰基)硫烷基]戊醇(CDPA)为可逆加成-断裂链转移(RAFT)试剂、甲苯为溶剂,在N_(2)氛围、80℃、反应24 h的条件下,通过RAFT聚合法制备了两嵌段共聚物(PEGMA-b-PCL)。将其自组装为胶束,作为纳米药物载体用于负载姜黄素(Cur)。采用FTIR、^(1)HNMR、GPC、SEM、DLS对PEGMA-b-PCL进行了表征,测试了胶束载体的载药和释药性能。结果表明,两嵌段共聚物数均相对分子质量范围为1478~7318,其具有较低的临界胶束浓度(在pH=5.0~7.4,范围为0.920~1.600 mg/L)。胶束载体粒径范围为68.34~186.93 nm。当n(CDPA)∶n(ε-CL)=1∶200时,胶束载药率和包封率最高,可达12.05%±0.29%和75.26%±2.41%。在不同pH环境下,药物缓释性能可达15 d,其中pH=5.0时的累积释药率最高,可达38.20%。

Construction and properties of venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres

The aim of this work is to develop a venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres(HMSMs).HMSMs were innovatively prepared with tetraethyl silicate(TEOS)as the precursor and volatile n-heptane as a soft template.The obtained HMSMs show a well-defined hollow structure with an average size of 967 nm and pore volume of 0.85 cm^(3)/g,implying it is a potential drug carrier.Subsequently,venlafaxine hydrochloride(VF)was absorbed in the HMSMs with a content of 37.67% or so.The sustained release effect is further measured by the dissolution in-strument at 37℃ and 50 rpm in ultrapure water.The results showed that the HMSMs/VF system shows good sustained release properties compared with sustained release tablets with hydroxypropyl meth-ylcellulose as the main component.This HMSMs sustained release system appears to be a promising candidate for a sustained drug release.

3D打印聚乳酸-纳米羟基磷灰石/壳聚糖/多西环素抗菌支架的性能

背景:聚乳酸具有良好的生物相容性和生物降解性,成为一种新型的骨科固定材料,然而该材料缺乏细胞识别信号,不利于细胞黏附和成骨分化,限制了其在生物材料中的应用。目的:3D打印聚乳酸-纳米羟基磷灰石/壳聚糖支架,评估其药物缓释及生物性能。方法:采用熔融沉积技术打印孔隙交互的多孔聚乳酸支架(记为PLA支架),将该支架浸泡于多巴胺溶液中制备聚乳酸-多巴胺支架(记为PLA-DA支架);将纳米羟基磷灰石投入壳聚糖溶液中,然后将PLA-DA支架浸没其中,制备聚乳酸-纳米羟基磷灰石/壳聚糖支架(记为PLA-nHA/CS支架),表征3组支架的微观形貌、孔隙率、水接触角与压缩强度。采用冷冻干燥法制备负载药物多西环素的PLA-nHA/CS支架(记为PLA-nHA/CS-DOX支架),表征其药物释放。将PLA、PLA-DA、PLA-nHA/CS、PLA-nHA/CS-DOX支架分别与MC3T3-E1细胞共培养,检测细胞增殖与成骨分化能力;将不同浓度的金黄色葡萄球菌悬液分别与4组支架共培养,采用抑菌圈实验检测支架的抗菌性能。结果与结论:①扫描电镜下可见PLA、PLA-DA支架表面致密光滑,PLA-nHA/CS支架表面可见纳米羟基磷灰石颗粒;PLA、PLA-DA、PLA-nHA/CS支架的孔隙率逐渐降低,压缩强度逐渐升高,PLA-nHA/CS支架的弹性模量满足松质骨要求;PLA-DA、PLA-nHA/CS支架的水接触角小于PLA支架;PLA-nHA/CS支架体外可持续释放药物达8 d。②CCK-8检测显示,4组支架均未显著影响MC3T3-E1细胞的增殖;PLA-DA组、PLAnHA/CS组、PLA-nHA/CS-DOX组细胞碱性磷酸酶活性均高于PLA组;茜素红染色显示,与PLA组相比,PLA-nHA/CS组、PLA-nHA/CS-DOX组细胞表现出较高的矿化水平。③抑菌圈实验显示PLA、PLA-DA支架无抗菌性能,PLA-nHA/CS支架具有一定的抗菌性能,PLA-nHA/CS-DOX支架具有超强的抗菌性能。④结果表明,PLA-nHA/CS-DOX支架具有良好的药物缓释性能、细胞相容性、促成骨性能及抗菌性能。

Ternary nanoparticle complex of ciprofloxacin exhibiting sustained release at gastric pH prepared by co-complexation with polyanions and an ionic amphiphile

Poor bioavailability of the broad spectrum antibiotic ciprofloxacin (CIP) is caused by its narrow absorption window in the stomach. With the aim of prolonging the gastric reside nee time of CIP, we prepared a ternary nano particle complex (nan oplex) of CIP by co-complexation w ith polya nions (sodium dextran sulfate (DXT)) and an anionic amphiphile (sodium dodecyl sulfate (SDS)). We investigated the effect of the charge ratio of DXT to SDS on the size, zeta potential, CIP payload, and CIP utilization rate of the CIP-DXTSDS nanoplex and its dissolution characteristics in simulated gastrointestinal fluids. Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry analyses showed that the ternary nanoplex was made up of amorphous C1P-DXT and crystalline CIP-SDS complexes. The size of the CIP-DXT-SDS nanoplex prepared at a >90% CIP utilization rate was 110-290 nm and it had a zeta potential of -16-39 mV, and CIP payload of 47-62%, depending on the charge ratio. At gastric pH, the CIP-DXT-SDS nanoplex prepared with a DXT:SDS charge ratio lower than 80:20 exhibited prolonged CIP release (60% dissolution after 8 h) compared with native CIP (100% dissolution after 1 h) and a binary CIP-DXT nanoplex (80% dissolution after 5 h), which was attributed to its lower solubility. The sustained release characteristics of the CIP-DXT-SDS nanoplex were comparable to those of existing CIP gastrorete ntive formulations.