Release Of Hydrophilic Drugs Research Articles

Preparation and drug release performance of amphiphilic medical hot‐melt pressure sensitive adhesives based on polystyrene‐isoprene‐styrene

AbstractHot‐melt pressure‐sensitive adhesives (HMPSAs) with polystyrene‐isoprene‐styrene (SIS) as the backbone material are widely used in transdermal drug delivery systems (TDDS) because of their high cohesive strength and drug‐carrying capacity. However, it is restricted by its high hydrophobicity when loaded with hydrophilic drugs. In this study, HMPSAs with amphiphilic properties were created by mixing SIS with fatty alcohol polyoxyethylene ether (AEO‐9) and polyethylene glycol (PEG) of different molecular weights to improve the ability of HMPSAs to deliver hydrophilic drugs. The effects of different molecular weights of PEG on the hydrophilicity of HMPSAs were also investigated. Additionally, gardenia glycosides and oleanolic acid were selected for drug release experiments. Compared to untreated HMPSAs, HMPSAs modified with AEO‐9 and PEG2000 could convert from hydrophobic to hydrophilic. The contact angle could be reduced from 91.8 to 25.6°, and the 24‐hour water absorption could be raised by 170%. The drug release experiments demonstrate that SIS/AEO‐9/PEG2000 enhances the release efficiency of the hydrophilic drug gardenia jasminoides by 69%. In summary, as a novel amphiphilic medicinal HMPSAs, SIS/AEO‐9/PEG offered a broad application promise in hydrophilic drug release.

The consequence of imine bond origination: Fabrication of rapid self-healing chitosan hydrogel as a drug delivery candidate for water-soluble drug

The burst release of hydrophilic drugs is a major challenge in the field of drug delivery which reduces the therapeutic value. Chitosan (CS) is one of the promising natural polymers along with incredible, non-toxicity, biocompatibility and biodegradability properties. In the present study, CS and crotonaldehyde (CA) were used for the fabrication of biocompatible, self-healing hydrogel through the formation of dynamic imine linkage. SEM images showed a cross-linked network-like microstructure of CS/CA hydrogel due to which significant swelling properties were also obtained. CS/CA hydrogel showed quick self-healing property within 2 min due to the formation of dynamic imine linkage between CS and CA which is further confirmed by rheology statistics. Good viscoelastic properties of the produced CS/CA hydrogel with different concentrations of CA were observed from rheology analysis (G′ = 1240 KPa). The proliferation of MCF-7 cells by MTT assay & CCK-8 in the presence of hydrogel proves its good biocompatibility and also showed controlled drug release of levofloxacin up to 50 h.

Development of Metal–Organic Frameworks (ZIF-8) as Low-Cost Carriers for Sustained Release of Hydrophobic and Hydrophilic Drugs: In Vitro Evaluation of Anti-breast Cancer and Anti-infection Effect

Development of Metal–Organic Frameworks (ZIF-8) as Low-Cost Carriers for Sustained Release of Hydrophobic and Hydrophilic Drugs: In Vitro Evaluation of Anti-breast Cancer and Anti-infection Effect

Smart and eco-friendly N-isopropylacrylamide and cellulose hydrogels as a safe dual-drug local cancer therapy approach

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.

Development and Evaluation of Core-Shell Nanocarrier System for Enhancing the Cytotoxicity of Doxorubicin/Metformin Combination Against Breast Cancer Cell Line

Breast cancer is the most invasive and life-threatening cancer in women. The treatment options are usually a combination of mastectomy, radiation therapy, hormonal therapy and chemotherapy. As a standard practice, doxorubicin (DOX) is one of the commonly used drugs for breast cancer treatment. However, DOX is known to have many harmful adverse effects including its cardiotoxicity. Hence, recent reports used metformin (MET), an anti-diabetic drug, as an adjuvant therapy to decrease the severity of DOX's adverse effects and to improve its ultimate therapeutic outcome. The current study is aimed at co-loading and enhancing the encapsulation efficiency of the hydrophilic DOX and MET in poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) with oil core for breast cancer treatment. The NCs were developed by single emulsification-solvent diffusion technique, and were optimized through using two types of oils, pluronics and PLGA (50:50) of different molecular weights followed by various physicochemical characterizations. The obtained DOX/MET-loaded NCs showed the size and polydispersity index (PDI) of 203.0 ± 3.4 nm and 0.081 ± 0.03, respectively with a surface charge of -2.15 ± 0.2 mV. The entrapment efficiency of DOX and MET were about 93.7% ± 2.9 and 70% ± 1.6, respectively. The developed PLGA core-shell NCs successfully sustained the DOX/MET release for more than 30 days. The in-vitro results showed a significant enhancement in DOX cytotoxic effect as well as a duplication in its apoptotic effect upon addition of MET for both free DOX/MET combination and DOX/MET-loaded PLGA NCs against MCF-7. Besides, flow cytometry demonstrated that the DOX/MET-loaded NCs possess their antitumor effect by preventing DNA replication and cell division. This study provides a promising facile, rapid and reproducible single emulsification-solvent diffusion technique for improving the encapsulation and release of hydrophilic drugs in nanocapsules for biomedical applications.

Brij Niosomes as Carriers for Sustained Drug Delivery─A Fluorescence-Based Approach to Probe the Niosomal Microenvironment.

Niosomes were prepared using a triad of polyoxyethylene alkyl ether surfactants. The focus was to elucidate the effects of varying alkyl chain length and varying hydrophilic headgroups on the structure of the niosomes, with an aim to design niosomes for efficient encapsulation and release of both hydrophobic and hydrophilic drugs. The phase transitions of the surfactants were ascertained by differential scanning calorimetry. It was found that the headgroup has a profound influence on the niosomal bilayer. Fluorescent probes Coumarin 153 (C-153) and 1,6-diphenyl-1,3,5-hexatriene were used to probe the structural integrity of the niosomal bilayer under stress conditions. Other aspects of the niosomes were probed by following the aggregation of the dyes fluorescein (FL) and Nile Red, red edge excitation shift, and fluorescence resonance energy transfer (FRET) between them. Fluorescence lifetime imaging microscopy provides proof of the exact location of the donor and acceptor dyes in the niosomes under FRET condition. It was also shown that the niosomes are efficient "carriers" for entrapment and controlled release of the chemotherapeutic drug 5-fluorouracil. It was found that a rigid niosomal bilayer leads to controlled drug release. The present work is relevant for the future use of these niosomes for cargo entrapment.

Hydrophilic drug release from electrospun membranes made out of thermo and pH-sensitive polymers

Electrospun fibers of the thermo-and pH sensitive poly(N-vinylcaprolactam-co-acrylic acid) (Poly(NVCL-co-AA) loaded with 10% and 30 wt% caffeine (Caf) were obtained by electrospinning and evaluated as potential drug delivery systems. Caffeine was used as a hydrophilic drug model, and poly(NVCL-co-AA) containing either 20 or 30 mol% AA was used as a carrier. The fibers morphology, as well as, their interaction with caffeine, were studied using different analytical techniques. The cytotoxicity of the different obtained fibers was evaluated by cell viability assays using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and mouse embryonic fibroblasts cell line (MEF cells). Caffeine release was studied at temperatures of 25 °C and 42 °C and pH of 1.2 and 7.4. Beadless copolymer fibers with diameters ranging from 1 μm to 2 μm were obtained. The addition of caffeine, which was in crystalline form after being encapsulated in the fibers, resulted in an increase of fiber diameter. The obtained membranes were found to be not cytotoxic. The entrapment of caffeine was greater for the copolymer containing 30 mol% AA due to a greater affinity of AA to caffeine. At a pH of 1.2 and at both temperatures of 25 °C and 42 °C, as well as, at a pH of 7.4 and a temperature of 42 °C, a Fickian diffusion mechanism for all copolymer fiber mats was observed. At a pH of 7.4 and 25 °C the release profile showed a high rate and followed a zero-order model, due to the fast dissolution of caffeine in water. These results indicated that thermo-and pH-sensitive poly(NVCL-co-AA) are promising candidates for controlled release of hydrophilic drugs.

Transport of Vitamin E from Ethanol/Water Solution into Contact Lenses and Impact on Drug Transport.

Purpose: Contact lens-based drug delivery has many advantages over eye drops including higher bioavailability and sustained release. Commercial contact lenses release drug rapidly necessitating integration of control-release mechanisms into the lenses such as incorporation of vitamin E diffusion barriers. In prior publications, vitamin E barriers are loaded by placing the lenses in vitamin E-ethanol solution, followed by the ethanol extraction. In this article, we investigate feasibility of manufacturing vitamin E barriers by soaking contact lenses in vitamin E dissolved in ethanol-water solutions to minimize swelling. Methods: Contact lenses are soaked in solutions of vitamin E dissolved in ethanol-water mixtures. The dynamics of vitamin E transport into the measured and fitted to diffusion equation to determine diffusivity and partition coefficient. Vitamin E loaded lenses are imaged and transport of hydrophilic drug timolol is measured. Results: The partition coefficient of vitamin E increases more than 5 and 10-fold when the water content in the loading solution reaches 15% and 25% (v/v), respectively. The solubility of vitamin E in the solutions decreases as water fraction increases but the increase in partition coefficient allows for loading > 20% vitamin E in the lens. The barriers manufactured by this approach are effective at sustaining release of glaucoma drug timolol. Conclusions: Vitamin E barriers can be incorporated into contact lenses by soaking in solutions of vitamin E in water and ethanol. Vitamin E barriers extended hydrophilic drug release and the reduced swelling is beneficial in minimizing the possibility of lens damage during loading of vitamin E.

Nanopolymers in drug delivery system

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. Among the synthetic and biodegradable polymers, aliphatic polyesters such as poly (glycolic acid), poly (lactic acid), poly (caprolactone) and polydioxanone, are most commonly used and applied to drug delivery systems. The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. In cancer, targeted polymeric NPs can be used to deliver chemotherapies to tumor cells with greater efficacy and reduced cytotoxicity on peripheral healthy tissues. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. Several nanotechnologies, mostly based on nanoparticles, can facilitate drug delivery to tumors like Hydrogels, Micelles and liposomes, Nanomaterial formulation, Nanosystems, Nanocells, Dendrimers, Nanotubes, etc. The larger the size of the drug, the more tumor penetration becomes a fundamental limitation. Lack of drug penetration becomes even more significant when using nanoparticles, as their perivascular accumulation and slow release pose a severe hindrance to drug delivery. The key advantages of nanoparticles are (1) improved bioavailability by enhancing aqueous solubility, (2) increasing resistance time in the body (increasing half life for clearance/increasing specificity for its cognate receptors and (3) targeting drug to specific location in the body (its site of action). Most important advantages offered by the polymeric nanoparticles include the following: (1) provide controlled release to the desired site, (2) provide stability to labile molecules (e.g., proteins), and (3) provide ability to modify surfaces with ligands for stealth and targeted drug delivery purposes.

Hydrophilic Excipient-Independent Drug Release from SLA-Printed Pellets.

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.

Polyamide/Poly(Amino Acid) Polymers for Drug Delivery.

Polymers have always played a critical role in the development of novel drug delivery systems by providing the sustained, controlled and targeted release of both hydrophobic and hydrophilic drugs. Among the different polymers, polyamides or poly(amino acid)s exhibit distinct features such as good biocompatibility, slow degradability and flexible physicochemical modification. The degradation rates of poly(amino acid)s are influenced by the hydrophilicity of the amino acids that make up the polymer. Poly(amino acid)s are extensively used in the formulation of chemotherapeutics to achieve selective delivery for an appropriate duration of time in order to lessen the drug-related side effects and increase the anti-tumor efficacy. This review highlights various poly(amino acid) polymers used in drug delivery along with new developments in their utility. A thorough discussion on anticancer agents incorporated into poly(amino acid) micellar systems that are under clinical evaluation is included.

Photo-responsive intraocular lens with on demand drug release for posterior capsule opacification prevention and improved biosafety

Posterior capsular opacification (PCO) is the most common complication after cataract surgery, which is caused by the adhesion, proliferation, migration and epithelial-mesenchymal transformation of the residual lens epithelial cells (LECs) in lens capsule. The drug eluting coating modification provides a powerful way to inhibit PCO incidence after IOL implantation. However, the uncontrolled proliferative drug brings intraocular biosafety issues when application. Therefore, developing new strategies with controlled drug release for PCO prevention is of great significance. In this investigation, a hydrophilic photo-responsive drug release coating was successfully constructed on IOL surface, which was verified through 1H•NMR, UV–Vis, FTIR and XPS. In vitro assay indicated that the IOL coating exhibited excellent anti-adhesion and anti-proliferation effects on LECs under irradiation. The photo-controlled drug release in vitro can be achieved by simply adjusting the intensity and time of irradiation. Finally, the surface-modified IOL was implanted in rabbit eyes and in vivo evaluation was carried out. In vivo assay demonstrated that the implantation of the modified IOL into eyes can significantly reduce the occurrence of PCO. Moreover, the modified IOL exhibited good biocompatibility and biosafety. We believe that this work will provide a synergistic strategy for effective prevention of PCO through a photo-controllable drug release coating on IOL surface.

Improvement of Drug Release and Compatibility between Hydrophilic Drugs and Hydrophobic Nanofibrous Composites.

Electrospinning is a flexible polymer processing method to produce nanofibres, which can be applied in the biomedical field. The current study aims to develop new electrospun hybrid nanocomposite systems to benefit the sustained release of hydrophilic drugs with hydrophobic polymers. In particular, electrospun hybrid materials consisting of polylactic acid (PLA):poly(ε-caprolactone) (PCL) blends, as well as PLA:PCL/halloysite nanotubes-3-aminopropyltriethoxysilane (HNT-ASP) nanocomposites were developed in order to achieve sustained release of hydrophilic drug tetracycline hydrochloride (TCH) using hydrophobic PLA:PCL nanocomposite membranes as a drug carrier. The impact of interaction between two commonly used drugs, namely TCH and indomethacin (IMC) and PLA:PCL blends on the drug release was examined. The drug release kinetics by fitting the experimental release data with five mathematical models for drug delivery were clearly demonstrated. The average nanofiber diameters were found to be significantly reduced when increasing the TCH concentration due to increasing solution electrical conductivity in contrast to the presence of IMC. The addition of both TCH and IMC drugs to PLA:PCL blends reduced the crystallinity level, glass transition temperature (Tg) and melting temperature (Tm) of PCL within the blends. The decrease in drug release and the impairment elimination for the interaction between polymer blends and drugs was accomplished by mobilising TCH into HNT-ASP for their embedding effect into PLA:PCL nanofibres. The typical characteristic was clearly identified with excellent agreement between our experimental data obtained and Ritger–Peppas model and Zeng model in drug release kinetics. The biodegradation behaviour of nanofibre membranes indicated the effective incorporation of TCH onto HNT-ASP.

Chitosan-based nanoparticles for controlled release of hydrophobic and hydrophilic drugs

Nanoparticles encapsulating different kinds of therapeutic drugs are promising drug delivery systems for controlling release and targeting tumor cells. Chitosan nanoparticles made by polyelectrolyte complexation were designed as drug carriers using doxorubicin (DOX)/5-fluorouracil (5-FU) as hydrophobic/hydrophilic model drugs. The sizes of nanoparticles were 235 ± 13 and 177 ± 7 nm with narrow distributions. The effects of the initial drug amount and pH of the medium on drug-controlled release properties were evaluated, the model-fitting results and release mechanisms were analyzed as well. For 5-FU-loaded chitosan nanoparticles, the controlled-release effect was superior to that of DOX, indicating that the polyelectrolyte complex nanoparticles were more suitable for hydrophilic drugs, particularly for negatively charged or electrically neutral drugs. Moreover, the release behaviors conformed with the first-order kinetic model, indicating that the nanoparticles were mainly released by diffusion during the drug release process; the system could also be fitted using the Higuchi model, showing that the entire drug release process was dominated by diffusion and supplemented by gradual dissolution. In all, the results suggested that chitosan nanoparticles made by polyelectrolyte complexation can be launched as a smart drug delivery system for cancer treatments.

The key role of the drug self-aggregation ability to obtain optimal nanocarriers based on aromatic-aromatic drug-polymer interactions

The efficient association and controlled release of hydrophilic and aromatic low molecular-weight drugs (HALMD) still remains a challenge due to their relatively weak interactions with excipients and strong affinity to water. Considering that a wide variety of drugs to treat chronic diseases are HALMD, their inclusion in polymeric nanoparticles (NPs) constitutes an attractive possibility by providing to these drugs with controllable physiochemical properties, preventing crisis episodes, decreasing dose-dependent side effects and promoting therapeutic adhesiveness. However, the strong interaction of HALMD with the aqueous medium jeopardizes their encapsulation and controlled release. In this work, the role of the self-assembly tendency of HALMD on their association with the aromatic excipient poly(sodium 4-styrensulfonate) (PSS) to form NPs is studied. For this aim, the widely used drugs amitriptyline (AMT), promethazine (PMZ), and chlorpheniramine (CPM) are selected due to their well described critical aggregation concentration (cac) (36 mM for AMT, 36 mM for PMZ, and 69.5 mM for CPM). These drugs undergo aromatic-aromatic interactions with the polymer, which stabilize their mutual binding, as seen by NMR. The simple mixing of solutions of opposite charged molecules (drug + PSS) allowed obtaining NPs. Importantly, comparing the three drugs, the formation of NPs occurred at significantly lower absolute concentration and significantly lower drug/polymer ratio as the cac takes lower values, indicating a stronger binding to the polymer, as also deduced from the respective drug/polymer dissociation constant values. In addition, the number of formed NPs is similar for all formulations, even though a much lower concentration of the drug and polymer is present in systems comprising lower cac. The obtained NPs are spheroidal and present size between 100 and 160 nm, low polydispersity (≤0.3) and negative zeta potential (from −30 to −60 mV). The association efficiency reaches values ≥ 83% and drug loading could achieve values up to 68% (never evidenced before for systems comprising HALMD). In addition, drug release studies are also significantly influenced by cac, providing more prolonged release for AMT and PMZ (lower cac), whose delivery profiles adjust to the Korsmeyer-Peppas equation. As a novelty of this work, a synergic contribution of drug self-association tendency and aromatic-aromatic interaction between the drug and polymers is highlighted, a fact that could be crucial for the rational design and development of efficient drug delivery systems.

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.

Investigation of the physicochemical stability of emulgels composed of poloxamer 407 and different oil phases using the Quality by Design approach

Emulgels can be prepared easily and provide the efficient drug release of hydrophilic and hydrophobic drugs. In this work, emulgel systems containing poloxamer 407, Carbopol 974P® or polycarbophil, sesame oil or isopropyl myristate were prepared using Quality by Design and the physicochemical damages were investigated regarding the preliminary stability studies. The physicochemical stability was assessed according to six freeze-thaw cycles, where the appearance, phase separation (fracture), droplet size and instability index were determined. The stable formulations were further characterized by sol-gel transition temperature. The freeze-thaw cycles and analytical centrifuging showed consistent and complementary results evidencing that lower concentration of bioadhesive polymers fostered the phase separation. Formulations showed to be polydisperse systems with droplet size dependent of the freeze-thaw cycles. The stable systems were selected by Quality by Design approach, and they showed suitable gelation temperature for future pharmaceutical and biomedical applications.

Electrospun collagen core/poly-l-lactic acid shell nanofibers for prolonged release of hydrophilic drug.

The development of sustained control drug release for delivering hydrophilic drugs has been challenging due to a burst release. Nanofibers are used as materials that enable efficient drug delivery systems. In this study, we designed drug-encapsulated core–shell nanofibers comprising a hydrophilic core of collagen (Col) incorporated with berberine chloride (BC), an anti-inflammatory and anti-cancer agent used as a model drug, and a hydrophobic shell of poly-l-lactic acid (PLLA). Long-term drug release profiles under both the physiological and hydrolysis-accelerated conditions were measured and analyzed using a Korsmeyer–Peppas kinetics model. We found that the Col/PLLA core–shell fiber achieved a controllable long-term release of the hydrophilic drug incorporated inside the core by the slow degradation of the PLLA shell to prevent the burst release while PLLA monolithic fibers showed early release due to the dissolution of drug and the following rapid hydrolysis of fibers. As shown by the results of Col/PLLA core–shell fiber under a hydrolysis-accelerated condition to promote the release of drugs test, it would provide sustained release over 16 days under physiological conditions. Here, the development of the nanomaterial for the long-term drug release of hydrophilic drugs was achieved, leading to its potential medical application including cancer treatment.

Intercalation of curcumin into liposomal chemotherapeutic agent augments apoptosis in breast cancer cells.

Resistance to common chemotherapeutic agents is a frequent phenomenon in late-stage breast cancers. An ideal system capable of the co-delivery of hydrophobic and hydrophilic chemotherapeutic agents can regulate the dosage and co-localization of pharmaceutical compounds and thereby improve the anticancer efficacy. Here, for the first time, we have intercalated curcumin (Cur) into a double-layered membrane of cisplatin (Cis) liposomes to obtain a dosage controlled co-delivery formulation, capable of inducing apoptosis in breast cancer cells. The concentrations of Cur and Cis in nanoliposome (Cur-Cis@NLP) were optimized by response surface methodology (RSM); RSM optimization showed 99.81 and 23.86% entrapment efficiency for Cur and Cis, respectively. TEM analysis demonstrated the fabrication of nanoparticles with average diameter of 100 nm. The anticancer and apoptotic effects of Cur-Cis@NLPs were also evaluated using MTT assay, fluorescent staining and flow cytometry assays. Cytotoxicity assessments of various Cur-Cis@NLPs concentrations demonstrated a concentration-dependent manner. In comparison to free and liposomal Cis, Cur-Cis@NLP reduced breast cancer cells' viability (82.5%) in a significant manner at a final concentration of 32 μg.mL-1 and 20 μg.mL-1 of Cur and Cis, respectively. Combination index values calculation of Cur-Cis@NLP showed an overall CI value <1, indicating synergetic effect of the designed co-delivery system. Additionally, flow cytometry assay demonstrated Cur-Cis@NLPs triggered apoptosis about 10-folds higher than liposomal Cis. This co-drug delivery system has a potential for the encapsulation and release of both hydrophobic and hydrophilic drugs, while taking the advantages of the reduced cytotoxic effect along with achieving high potency.

Self-healing multilayer films for simultaneous release of hydrophilic and hydrophobic drugs

ABSTRACT Coloading and codelivery of hydrophilic and hydrophobic drugs as techniques for effective therapy have drawn attention but still present a challenge owing to the opposite nature of both drugs. Therefore, determining a convenient method for coloading and coreleasing hydrophilic and hydrophobic drugs in the development of biomedical devices is important. We constructed multilayer films with a microporous structure for the successful coloading of hydrophilic and hydrophobic drugs. The multilayer films were fabricated using chitosan (CS) and polyacrylic acid (PAA) via layer-by-layer self-assembly. A quartz crystal microbalance (QCM) was used to investigate the self-assembly of (CS/PAA) in films. With a low pH to change the inner structure of the multilayer films, these microporous structures exhibit humidity responsiveness and can return to the original compact structures by treatment with 100% relative humidity. The microporous films can simultaneously load a large number of hydrophobic drugs (tetracycline) and hydrophilic model drugs (Rhodamine B) by wicking and subsequent micropore self-healing. The loading and release ratio of the two drugs in the microporous films is consistent with the initial loading ratio in the solution, providing a good platform for coloading and codelivery of hydrophobic and hydrophilic drugs in biomedical applications.