Sustained Drug Release Behavior Research Articles

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens.

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Thermosensitive selenium hydrogel boosts antitumor immune response for hepatocellular carcinoma chemoradiotherapy

Hepatocellular carcinoma (HCC) possesses high mortality rate and becomes the third most common cause of cancer death. Searching new therapeutic strategies for HCC are still urgently needed. In situ thermosensitive hydrogels loading with chemotherapeutics have attracted increasing attention for HCC due to their superior advantages including high drug loading and sustained drug release behavior. Herein, we developed a novel in situ injection thermosensitive hydrogel system based on Poloxamer 407 (P407) and selenium nanoparticle loading with DOX (PPS-SeNPs@DOX) for localized synergistic chemoradiotherapy of HCC. The synthesized PPS-SeNPs@DOX hydrogel system showed a better phase transition temperature at 32 ℃, and the mechanical properties were not affected under X-ray irradiation, which suggests the stability of the synthesized hydrogel. The localized injection of PPS-SeNPs@DOX combined with radiotherapy was found to significantly suppress HepG2 tumors growth in vivo, as evidenced by the decreased tumor volume, tumor weight and Ki67 expression. Furthermore, the synergistic anticancer effects in orthotopic Hepa1-6 tumors were also found in the combination treatment of PPS-SeNPs@DOX and X-ray irradiation with the involvement of antitumor immunity activation accompanied by the upregulated population of CD8+ T, M1 and NK1.1 cells and downregulated population of Gr1 cells after single in situ injection. Taken together, this study presents a novel in situ injection thermosensitive hydrogel system for the chemoradiotherapy of HCC, which may provide a solid foundation for designing local delivery platform for unresectable HCC therapy.

Rapidly separable microneedle patch for the controlled and sustained release of 5-fluorouracil

5-Fluorouracil (5-FU) is frequently used in the treatment of tumors and swollen tissues. However, traditional administration methods can result in poor patient compliance and require to administrate frequently due to the short T1/2 of 5-FU. Herein, the 5-FU@ZIF-8 loaded nanocapsules were prepared using multiple emulsion solvent evaporation methods to enable the controlled and sustained release of 5-FU. To decrease the drug release rate and enhance patient compliance, the obtained pure nanocapsules were added to the matrix to fabricate rapidly separable microneedles (SMNs). The entrapment efficiency (EE%) of 5-FU@ZIF-8 loaded nanocapsules was in the range of 41.55–46.29 %, and the particle size of ZIF-8, 5-FU@ZIF-8, and 5-FU@ZIF-8 loaded nanocapsules were 60 nm, 110 nm, and 250 nm respectively. According to the release study in vivo and in vitro, we concluded that 5-FU@ZIF-8 nanocapsules could achieve the sustained release of 5-FU and that the burst release of nanocapsules could be elegantly handled by incorporating nanocapsules into the SMNs. What's more, the use of SMNs could improve patient compliance due to the rapid separation of needles and backing of SMNs. The pharmacodynamics study also revealed that the formulation would be a better choice for the treatment of scars due to the advantages of painlessness, separation ability, and high delivery efficiency. In conclusion, the SMNs containing 5-FU@ZIF-8 loaded nanocapsules could serve as a potential strategy for some skin diseases therapy with controlled and sustained drug release behavior.

Investigation of the structural, photoluminescence properties, bioactivity and 5-fluorouracil delivery behavior of Dy3+ and Dy:Eu3+-doped bioactive glasses

Nowadays fluorescent biomaterials gained crucial interest in the biomedical field. Here we report the sol-gel synthesis and characterization of Dy3+ and Dy:Eu3+ co-doped bioactive glass powders. Structural, morphological, and photoluminescence (PL) characteristics of the prepared powders were investigated in detail. Additionally, in vitro hydroxyapatite forming ability and the anticancer drug (5-Fluorouracil) release behavior were investigated with respect to time. The influence of drug loading and delivery on the PL properties was monitored. Results showed that the highest PL intensity was obtained for the 5%Dy:Eu3+ co-doped glass samples. The incorporation of rare-earth ions into the glass network did not cause a significant difference in the structural properties. In vitro conversion experiments, performed in simulated body fluid, indicated that the incorporation of Dy3+ to the glass network enhanced the hydroxyapatite deposition however Dy:Eu3+ co-doping slightly decreased the bioactivity. Drug-loaded bioactive glass powders exhibited sustained drug release behavior to the phosphate buffered saline (PBS) medium. An increase was obtained in the fluorescence intensities for 5-FU-loaded samples followed by a further increase in emissions for the powders released drug to the PBS medium. The findings of the study may be useful for monitoring the degradation of bioactive glasses, conversion to hydroxyapatite as well as drug delivery after implantation.

Monodisperse CaCO3-loaded gelatin microspheres for reversing lactic acid-induced chemotherapy resistance during TACE treatment

Transarterial chemoembolization (TACE) is an important approach for the treatment of unresectable hepatocellular carcinoma (HCC). However, the lactic acid-induced acidic tumor microenvironment (TME) may reduce the therapeutic outcome of TACE. Herein, monodispersed gelatin microspheres loaded with calcium carbonate nanoparticles (CaNPs@Gel-MS) as novel embolic agents were prepared by a simplified microfluidic device. It was found that the particle size and homogeneity of as-prepared CaNPs@Gel-MS were strongly dependent on the flow rates of continuous and dispersed phases, and the inner diameter of syringe needle. The introduction of CaNPs provided the gelatin microspheres with an enhanced ability to encapsulate the chemotherapeutic drug of DOX, as well as a pH-responsive sustained drug release behavior. In vitro results revealed that CaNPs@Gel-MS could largely increase the cellular uptake and chemotoxicity of DOX by neutralizing the lactic acid in the culture medium. In addition, CaNPs@Gel-MS exhibited an excellent and persistent embolic efficiency in a rabbit renal model. Finally, we found that TACE treatment with DOX-loaded CaNPs@Gel-MS (DOX/CaNPs@Gel-MS) had a much stronger ability to inhibit tumor growth than the DOX-loaded gelatin microspheres without CaNPs (DOX@Gel-MS). Overall, CaNPs@Gel-MS could be a promising embolic microsphere that can significantly improve anti-HCC ability by reversing lactic acid-induced chemotherapy resistance during TACE treatment.

Injectable carboxymethyl chitosan/nanosphere-based hydrogel with dynamic crosslinking network for efficient lubrication and sustained drug release

The typical symptoms of arthritis are inflammation and lubrication deficiency in joints, which increase wear of articular cartilage along with pain of patients. In the present study, one kind of novel macromolecular/microsphere-based injectable hydrogels (CMC-ODex NPs) with dual functionalities of drug release and lubrication, was fabricated via dynamic Schiff base crosslinking network between carboxymethyl chitosan (CMC) and oxidation dextran nanoparticles (ODex NPs). The CMC-ODex NPs hydrogels exhibited typical viscosity-thinning phenomenon at wide range of shear rates and obvious gel-sol transition feature at specific strain. As a result, CMC-ODex NPs hydrogels presented low friction coefficient at the sliding interface of bovine articular cartilages, resulting from the boundary lubrication of hydrogel and the rolling friction effect of ODex NPs. Furthermore, the anti-inflammatory drug (dexamethasone, DXM) encapsulated in ODex NPs exhibited sustainable drug release behavior during the dynamic shearing process, which making CMC-ODex NPs hydrogels possessed good and stable anti-inflammatory effect. CMC-ODex NPs hydrogels was prepared without utilizing any toxic agents, thus demonstrated excellent cytocompatibility. Our experimental results reveal the CMC-ODex NPs hydrogels is promising to be used as functional lubricant for inhibiting the development of arthritis.

Hybrid Polydimethylsiloxane (PDMS) Incorporated Thermogelling System for Effective Liver Cancer Treatment.

For the delivery of anticancer drugs, an injectable in situ hydrogel with thermal responsiveness and prolonged drug release capabilities shows considerable potential. Here, we present a series of thermosensitive in situ hydrogels that serve as drug delivery systems for the treatment of liver cancer. These hydrogels were created by utilizing the polydimethylsiloxane (PDMS) oligomer, polyethylene glycol (PEG) and polypropylene glycol (PPG)'s chemical cross-linking capabilities. Doxorubicin (DOX) was encapsulated in a hydrogel with a hydrophobic core and hydrophilic shell to enhance DOX solubility. Studies into the behavior of in situ produced hydrogels at the microscopic and macroscopic levels revealed that the copolymer solution exhibits a progressive shift from sol to gel as the temperature rises. The hydrogels' chemical composition, thermal properties, rheological characteristics, gelation period, and DOX release behavior were all reported. Subcutaneous injection in mice was used to confirm the injectability. Through the in vitro release of DOX in a PBS solution that mimics the tumor microenvironment, the hydrogel's sustained drug release behavior was confirmed. Additionally, using human hepatocellular hepatoma, the anticancer efficacy of thermogel (DEP-2@DOX) was assessed (HepG2). The carrier polymer material DEP-2 was tested for cytotoxicity using HepG2 cells and its excellent cytocompatibility was confirmed. In conclusion, these thermally responsive injectable hydrogels are prominent potential candidates as drug delivery vehicles for the treatment of hepatocellular carcinoma.

Levosulpiride-loaded nanostructured lipid carriers for brain delivery with antipsychotic and antidepressant effects

AimsHerein, we investigate the potential of levosulpiride-loaded nanostructured lipid carriers (LEVO-NLCs) for effective brain delivery with anti-psychotic and antidepressant effects. Main methodsMicro-emulsion method was used to prepare LEVO-NLCs, followed by its optimization using Design Expert®, investigation of the particles properties and entrapment efficiency (%EE). Moreover, in-vitro release, in-vivo plasma and brain kinetic studies of LEVO-NLCs were executed. Anti-psychotic activity of LEVO-NLCs was accomplished in LPS-induced psychosis mice model. Additionally, expressions of neuro inflammatory mediators, neurodegeneration and neuro-inflammation in brain tissues was investigated. Key findingsThe optimized LEVO-NLCs were rounded shaped nanoparticles (157.2 nm) with suitable zeta potential (−29.6 mV), low PDI (0.395) and high EE (83.67 %). No chemical interactions were found, however, the crystalline drug was changed to amorphous. LEVO-NLCs displayed sustained drug release behavior when compared with drug suspension. Moreover, a meaningfully higher AUC (106,642.27 ± 876.44 ng.h/mL) and Cmax (38,534.72 ± 2344.10 ng/mL) of the LEVO-NLCs in brain was observed as compared to the AUC (15,684.33 ± 1005.49 ng.h/mL) and Cmax (7717.56 ± 871.23 ng/mL) of LEVO-Suspension. Similar profiles of both the formulations were perceived in plasma pharmacokinetic studies. Furthermore, LEVO-NLCs exhibited a meaningfully improved anti-psychotic activity in LPS-induced psychosis mice model with reduced immobility time and enhanced struggling time. Likewise, treatment with LEVO-NLCs showed reduced levels of neuro inflammatory markers (p-NF-κB and COX-2) in LPS-induced mice. Additionally, no neuro-degeneration and neuro-inflammation in brain tissues treated with LEVO-NLCs mice group was detected. SignificanceThese results concluded that NLCs may effectively be used for the brain delivery of various active pharmaceutical agents with enhanced biopharmaceutical performance.

Caffeic Acid Modified Nanomicelles Inhibit Articular Cartilage Deterioration and Reduce Disease Severity in Experimental Inflammatory Arthritis.

Inflammation plays an important role in the development of rheumatoid arthritis (RA). NR4A1 is an anti-inflammatory orphan nuclear receptor involved in protection from inflammatory stimuli in RA. In this study we have explored the anti-inflammatory potential of the FDA-approved drug 9-aminoacridine (9AA) and the natural compound caffeic acid (CA) conjugated to nanomicelles for the treatment of RA. We have synthesized methoxy polyethylene glycol polycaprolactone block copolymer (mPEG-b-PCL) by ring opening polymerization of ε-caprolactone. Then, we conjugated the hydrophilic caffeic acid (CA) with mPEG-b-PCL micelles via Steglich esterification and incorporated the 9AA drug. These nanomicelles were formulated by the solvent evaporation method with a size distribution around 190 nm and showed maximum drug loading capacity along with sustained drug release behavior. Furthermore, we tested the therapeutic potential of the formulated 9AA-encapsulated CA-conjugated nanomicelles (9AA-NMs) against an experimental RA model. We observed promising results which showed alleviation of arthritic symptoms by reducing inflammation, joint damage, bone erosion, and swelling. Further, collagen destruction was significantly reduced in articular cartilage, as shown by safranin-O and toluidine blue staining. The protective mechanism might be due to the simultaneous inhibition of NF-κB by 9AA and CA, whereas the activation of NR4A1 by 9AA leads to the suppression of HIF-1α. This combined therapeutic effect of 9AA and CA has enhanced the therapeutic efficacy of 9AA-NM and markedly reduced the severity of inflammatory arthritis. Unlike existing drugs for pain management and with limited efficacy, 9AA-NM exerted a disease-relevant activation/blockade that alleviated inflammation and exhibited marked therapeutic efficacy against RA.

Enzyme-Enhanced Codelivery of Doxorubicin and Bcl-2 Inhibitor by Electrospun Nanofibers for Synergistic Inhibition of Prostate Cancer Recurrence.

One of the great challenges of postoperative prostate cancer management is tumor recurrence. Although postoperative chemotherapy presents benefits to inhibit unexpected recurrence, it is still limited due to the drug resistance or intolerable complications of some patients. Electrospun nanofiber, as a promising drug carrier, demonstrating sustained drug release behavior, can be implanted into the tumor resection site during surgery and is conductive to tumor inhibition. Herein, we fabricated electrospun nanofibers loaded with doxorubicin (DOX) and ABT199 to synergistically prevent postoperative tumor recurrence. Enzymatic degradation of the biodegradable electrospun nanofibers facilitated the release of the two drugs. The primarily released DOX from the electrospun nanofibers effectively inhibited tumor recurrence. However, the sustained release of DOX led to drug resistance of the tumor cells, yielding unsatisfactory eradication of the residual tumor. Remarkably, the combined administration of DOX and ABT199, simultaneously released from the nanofibers, not only prolonged the chemotherapy by DOX but also overcame the drug resistance via inhibiting the Bcl-2 activation and thereby enhancing the apoptosis of tumor cells by ABT199. This dual-drug-loaded implant system, combining efficient chemotherapy and anti-drug resistance, offers a prospective strategy for the potent inhibition of postoperative tumor recurrence.

Self-assembly hydrogels of therapeutic agents for local drug delivery.

Advanced drug delivery systems are of vital importance to enhance therapeutic efficacy. Among various recently developed formulations, self-assembling hydrogels composed of therapeutic agents have shown promising potential for local drug delivery owing to their excellent biocompatibility, high drug-loading efficiency, low systemic toxicity, and sustained drug release behavior. In particular, therapeutic agents self-assembling hydrogels with well-defined nanostructures are beneficial for direct delivery to the target site via injection, not only improving drug availability, but also extending their retention time and promoting cellular uptake. In brief, the self-assembly approach offers better opportunities to improve the precision of pharmaceutical treatment and achieve superior treatment efficacies. In this review, we intend to cover the recent developments in therapeutic agent self-assembling hydrogels. First, the molecular structures, self-assembly mechanisms, and application of self-assembling hydrogels are systematically outlined. Then, we summarize the various self-assembly strategies, including the single therapeutic agent, metal-coordination, enzyme-instruction, and co-assembly of multiple therapeutic agents. Finally, the potential challenges and future perspectives are discussed. We hope that this review will provide useful insights into the design and preparation of therapeutic agent self-assembling hydrogels.

Integration of metformin-loaded mesoporous bioactive glass nanoparticles and free metformin into polymer microneedles for transdermal delivery on diabetic rats

Transdermal delivery provides a suitable and painless self-administration for diabetic patients. In this work, the polymer microneedles (MNs) integrated with mesoporous bioactive glass nanoparticles (BGNs) for transdermal delivery of metformin (Met) have been developed for regulation of blood glucose levels (BGLs) on diabetic rats. The obtained MNs system contains free Met and Met-loaded BGNs (Met/BGNs) for independently controlling the kinetics of anti-diabetic drug during the treatment. Once these MNs are penetrated into the skin, the free Met is firstly released due to the swelling and degradation of matrix material of MNs. And then the loaded Met is slowly seep through the microchannels of BGNs to form a sustained drug release behaviors and a better hypoglycemic effect, suggesting the potential of this new transdermal delivery system as substitutes for multiple daily injections.

Theranostics platform of Abemaciclib using magnetite@silica@chitosan nanocomposite

The current study was designed to synthesize a nanoformula comprising of magnetite nanoparticles (MN) with mesoporous silica (MS), which was in turn coated with chitosan (CS) and further loaded with a chemotherapeutic agent, Abemaciclib (ABE). The prepared formula, MN@MS@CS@ABE, was characterized by XRD, FTIR, HRTEM, FESEM, DLS, VSM, BET, and BJH. The ABE loading capacity and entrapment efficiency were calculated, and an in vitro drug release experiment was conducted. Cytoxicity was studied by the MTT assay. The formula was investigated as an anticancer agent versus MCF-7 cells by performing Annexin V-FITC flow cytometry and cell cycle analysis. Furthermore, we examine the formula as a contrast agent in magnetic resonance imaging (MRI). ABE loading and encapsulation efficiency were 24.2 % and 63.4 %, respectively. The formula demonstrated sustained drug release behavior for 72 h. The MTT assay revealed a higher cytotoxicity of free ABE in MCF-7 cells compared to MN@MS@CS@ABE. Flow cytometry revealed early and late phases of apoptosis and necrosis with different percentages. The formula stimulated a reduction in signal intensity in the MR T2-weighted imaging technique. In conclusion, the current study developed a nanoformula which could be a promising theranostic agent in cancer therapy and diagnosis.

Aloe vera and ofloxacin incorporated chitosan hydrogels show antibacterial activity, stimulate angiogenesis and accelerate wound healing in full thickness rat model.

Burns are potentially fatal and physically debilitating injuries, causing psychological and physical scars and result in chronic disabilities. A well vascularized wound bed is required to achieve complete and scar free wound closure. For many centuries, a variety of herbal plants have been used for wound healing, among these aloe vera (AV) has been found to be very effective in wound healing. Secondly, the main reason for delayed wound healing is bacterial infections. Ofloxacin (OX) has been reported as an active antibacterial drug for topical infections and it is effective against both positive and negative bacterial strains. In current research three different concentrations of OX (0.5, 2.5, and 5mg) were loaded into chitosan (CS)/AV based hydrogels prepared by freeze gelation. The surface morphology of prepared CS/AV based OX loaded hydrogels were evaluated by scanning electron microscopy (SEM). In drug release analysis, 0.5mg OX loaded hydrogel showed a sustained drug release behavior over 3 days period. An effective dose dependent antibacterial activity was exhibited by OX loaded hydrogels. Alamar Blue cells viability assay revealed that 0.5mg OX hydrogel (CA 0.5 OX) showed comparatively better 3T3 fibroblast cells proliferation as compared to CA 2.5 OX (2.5mg OX) and CA 5 OX hydrogel (5mg OX). Moreover, all OX loaded hydrogels showed good angiogenic activity in CAM bioassay while higher angiogenic potential was observed from CA 0.5 OX containing comparatively lower concentration of OX. These OX incorporated CS/AV based hydrogels are promising wound dressings for future clinical use.

Bioresponsive inulin‐azobenzene nanostructures for targeted drug delivery to colon

AbstractHere, a series of amphiphilic inulin‐azobenzene (IAb) conjugates has been synthesized by the reaction of inulin, a naturally occurring polysaccharide, with varying amounts of 6‐(3‐(4‐[4‐dimethylaminophenylazo]‐phenyl)‐thioureido)‐hexanoic acid (Azo‐ahx), an azobenzene linker. The resulting IAb conjugates (IAb‐1, IAb‐2 and IAb‐3 with 1, 3, and 5% substitution of the linker, respectively) self‐assembled into nanostructures in aqueous environment, which were then used to encapsulate the hydrophobic drug molecules, ornidazole (OZ) and 5‐fluorouracil (FU). Drug loaded and unloaded nanostructures were subjected to characterization by spectroscopic and dynamic light scattering (DLS) techniques. The sustained drug release behavior of these nanostructures was studied by dialysis bag method at different pH values. Enzyme‐responsive drug release behavior was investigated under the influence of inulinase. Besides, the best formulation, IAb‐1, not only showed antioxidant potential but also exhibited good wound healing properties as evidenced by in vitro scratch assay in HaCaT cells. The self‐assembled nanostructures of IAb‐1 were found be non‐toxic to cells even up to 700 μg/ml as tested by MTT assay on HEK 293 and HeLa cells. In conclusion, the potential of self‐assembled drug loaded inulin‐azo nanostructures has been demonstrated for the targeted drug delivery applications.

Bioinspired Hydroxyapatite Coating Infiltrated with a Graphene Oxide Hybrid Supramolecular Hydrogel Orchestrates Antibacterial and Self-Lubricating Performance.

Hydroxyapatite (HA) bioceramic coating has been extensively applied for the modification of metallic implants to improve their biocompatibility and service life after implantation. Unfortunately, HA coating often suffers from high friction, severe wear, and bacterial invasion, which restrict its application in artificial joints. According to a bioinspired soft/hard combination strategy, a novel HA composite coating that is infiltrated with a vancomycin-loaded graphene oxide (GO) hybrid supramolecular hydrogel is developed via vacuum infiltration and a subsequent host-guest interaction-induced self-assembly process. The holes of textured HA ceramic coating act just like a "magic pocket", offering a stable container to form and store GO hybrid hydrogels and even to recycle wear debris as well. The drug-loaded hybrid hydrogels stored in textured HA coating possess a unique shear force and/or frictional heat triggered gel-sol transition and sustained drug release behavior, acting like the extrusion of synovial fluid during articular cartilage movement, leading to a remarkable self-lubrication, anti-wear performance, and promising antibacterial property against Staphylococcus aureus. The friction coefficient and wear rate of composite coating reduced by nearly five times and three orders of magnitude compared with textured HA coating, respectively, which benefited from the synergistic lubricate effect of cyclodextrin-based pseudopolyrotaxane supramolecular hydrogel and GO lubricants.

Optimization of Maduramicin Ammonium-Loaded Nanostructured Lipid Carriers Using Box-Behnken Design for Enhanced Anticoccidial Effect against Eimeria tenella in Broiler Chickens.

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD–NLCs) were prepared to overcome the defects of MAD by using highly soluble nanostructured lipid carriers (NLCs). The formulation was optimized via a three-level, three-factor Box–Behnken response surface method. Then, the optimal MAD–NLCs were evaluated according to their hydrodynamic diameter (HD), zeta potential (ZP), crystal structure, encapsulation efficiency (EE), drug loading (DL), in vitro release, and anticoccidial effect. The optimal MAD–NLCs had an HD of 153.6 ± 3.044 nm and a ZP of −41.4 ± 1.10 mV. The X-ray diffraction and Fourier-transform infrared spectroscopy results indicated that the MAD was encapsulated in the NLCs in an amorphous state. The EE and DL were 90.49 ± 1.05% and 2.34 ± 0.04%, respectively, which indicated that the MAD was efficiently encapsulated in the NLCs. In the in vitro study, the MAD–NLCs demonstrated a slow and sustained drug release behavior. Notably, MAD–NLCs had an excellent anticoccidial effect against Eimeria tenella in broiler chickens. In summary, MAD–NLCs have huge potential to form a new preparation administered via drinking water with a powerful anticoccidial effect.

The release kinetic of drug encapsulated poly(L-lactide-co-ɛ-caprolactone) core-shell nanofibers fabricated by emulsion electrospinning

Core-shell nanofibers for biomedical applications have been successfully prepared by emulsion electrospinning, utilizing the model drug Tetracycline hydrochloride (TCH) water solution as the “aqueous phase” and hydrophobic polymer solution as the “organic phase.” The morphology of nanofibers was assessed by scanning electron microscopy (SEM) and the core-shell structure was confirmed by inverted fluorescence microscopy and transmission electron microscopy (TEM). The improved hydrophilicity might be caused by the presence of the emulsifier Span 80 on the surface of the nanofibers. The mechanical properties study showed that core-shell nanofibers membranes were softer and more elastic than blended nanofibers. In vitro drug release study showed that the TCH could release continuously for 34 days. The release mechanism of the nanofibers followed Fickian diffusion at low drug efficiency, but drug diffusion was the best fit with the First-order kinetic model when increasing drug loading rates. Overall, emulsion core-shell nanofibers could be used as a promising drug reservoir for sustained and continuous drug release behaviors. Meanwhile, the study of drug release kinetics was used in conjunction with model drug properties to develop a wider range of nanofibers carriers and biomaterials.

Drug-loaded oleic-acid grafted mesoporous silica nanoparticles conjugated with α-lactalbumin resembling BAMLET-like anticancer agent with improved biocompatibility and therapeutic efficacy.

Despite its prominent therapeutic efficacy, chemotherapy has raised serious concerns due to the severe adverse effects and multidrug resistance evoked, which propels the search for safe and green therapeutic agents. BAMLET (bovine α-lactalbumin made lethal against tumor cell) is a well-known protein-based anticancer agent of selective tumoricidal activity. Here, we prepared oleic acid-modified mesoporous silica nanoparticles (OA-MSNs) conjugated with bovine α-lactalbumin, a lipoprotein complex resembling BAMLET formed on the surface of MSNs (MSN-BAMLET) to load the anticancer drug of docetaxel (DTX). Compared to that of OA-MSNs/DTX, the obtained MSN-BAMLET/DTX with a sustained and pH-responsive drug release behaviors exhibited good biocompatibility and enhanced cytotoxic effect against cancer cells. Moreover, the presence of lipoprotein complex in MSN-BAMLET contributed to the improved dispersion of the composite in solution and the inhibitory effect on the migration of cancer cells. Furthermore, the adsorption profiles of protein corona on the obtained nanoparticles were analyzed. It was found that the marked low amount and abundance of plasma proteins were adsorbed on the α-lactalbumin coated siliceous composite demonstrated its long circulation property. Finally, in vivo study showed that MSN-BAMLET/DTX contributed to the effective cancer ablation and the prolonged survival. Therefore, the constructed MSN-BAMLET of the mesoregular structure and peculiar tumoricidal effect provides a manipulable nanoplatform as drug nanocarrier for therapeutic applications.

Synthesis and Characterization of Antibiotic-Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections.

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr–mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr–mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer–Emmett–Teller (BET) specific surface area and pore diameter was found to be about 182.35 m2/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr–mpHANCs (AMX@Ctr–mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr–mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr–mpHANCs. It was observed in both studies that AMX@Ctr–mpHANCs showed a significant reduction in the bacterial growth of S. aureus, E. coli, and P. aeruginosa as compared to Ctr–mpHANCs with no bacteria-killing. Thus, we proposed that Ctr–mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.