pH-responsive Drug Release Research Articles

Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo.

Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of - 23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-responsive sustained drug release profile over a period of 240 h following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments demonstrated that the targeted nanodelivery system provided selective internalization and strong growth inhibition effects of about 45 and 51% against nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that these phenomena were not observed in nucleolin-negative cells (CHO). The preclinical studies revealed that a single-dose intravenous injection of the targeted nanodelivery system into 4T1-bearing mice inhibited tumor growth by 1.7- and 1.4-fold more efficiently than the free drug and the non-targeted nanodelivery system, respectively. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.

The preparation of pH-sensitive doxorubicin prodrug for enhanced antitumor efficacy

We have produced a micelle nanoparticle with intrinsic pH response, which is formed by self-assembled amphiphilic polyethylene glycol-Schiff-doxorubicin (PEG-Schiff-DOX) prodrug. These nanoparticles can maintain stability well under normal conditions and last for more than a week, but they will rapidly decompose in slightly acidic environments. The concentration of DOX in the nano solution is high with the drug loading ratio of 49.4%. This pH-responsive drug release behavior may lead to higher intracellular drug concentrations and prolonged action times. CCK-8 assays have shown that the nanosuspension exhibits superior anti-tumor activity against HeLa cells compared to free DOX. It is believed that these nanoparticle-based prodrug have great potential for developing DOX formulations for cancer therapy.

Biodegradable pectin-based thermo-responsive composite GO/hydrogel with mussel inspired tissue adhesion for NIR enhanced burn wound healing

Thermo-responsive hydrogels with biodegradability have great application in biomedical areas, while the Poly(N-isopropylacrylamide) (PNIPAM) based hydrogels exhibiting lower critical solution temperature (LCST) around body temperature have shown promising applications in diverse areas such as drug delivery, tissue engineering, and wound repairing. In this study, PNIPAM based thermo-responsive copolymer with ketone functional group was polymerized and the LCST was regulated to body temperature, then biodegradable self-healing hydrogels with injectability were fabricated by cross-linking the thermo-responsive copolymers with dopamine functionalized pectin hydrazide (PDAH). The hydrogel exhibited good mechanical strength, excellent biocompatibility and thermo-responsive sustained drug release process. The nano-graphene oxide (GO) was incorporated to design near-infrared (NIR) sensitive nanocomposite hydrogel to serve as photothermal enhanced wound dressing with vancomycin loading. The composite hydrogel also showed pH-responsive drug release behavior and the NIR irradiation also accelerated the release rate based on photothermal induced phase transition. More importantly, the nanocomposite hydrogel with vancomycin loading and photothermal property can promoted burn wound repairing rate by inhibiting the bacterial growth. As a result, this GO composite hydrogel (GO/hydrogel) could act as NIR triggered photo-thermal enhanced drug delivery platform for promoted wound repairing in the near future.

Dual Rifampicin and Isoniazid Mannose-Decorated Lipopolysaccharide Nanospheres for Macrophage- Targeted Lung Delivery.

Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity. This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity. The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers. Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.

Mn2+-doped hollow mesoporous Prussian blue nanocubes for tumor synergistic therapy

To leverage the exceptional biomedical properties of Prussian blue (PB), we synthesized Mn2+-doped hollow mesoporous Prussian blue nanocubes (Mn-HMPB) via a straightforward ion-exchange method to enhance the photothermal/chemo synergistic therapeutic efficiency. The precise modulate of nanostructures of Mn-HMPB with notable photothermal conversion efficiencies and quercetin (QUE) loading capacities. Introducing Mn2+ doping in Mn-HMPB enables pH-responsive drug release under different physiological conditions. The systematic in vitro experiments have verified that the drug release and NIR irradiation mediated by Mn-HMPB@QUE nanocubes significantly inhibit the proliferation of Hela cells, resulting in an exceptional synergistic therapeutic outcome compared to single Mn-HMPB nanocubes or free QUE. Moreover, Mn-HMPB nanocubes exhibits outstanding biocompatibility and stability in psychological environment, positioning it as a reliable nanomedicine candidate. In conclusion, this study findings demonstrate the effective inhibition of growth and metastasis of Hela cells by Mn-HMPB@QUE nanocubes, exhibiting their potential as a versatile nanoplatform for tumor therapy.

In Vitro/In Vivo Preparation and Evaluation of cRGDyK Peptide-Modified Polydopamine-Bridged Paclitaxel-Loaded Nanoparticles.

Cancer remains a disease with one of the highest mortality rates worldwide. The poor water solubility and tissue selectivity of commonly used chemotherapeutic agents contribute to their poor efficacy and serious adverse effects. This study proposes an alternative to the traditional physicochemically combined modifications used to develop targeted drug delivery systems, involving a simpler surface modification strategy. cRGDyK peptide (RGD)-modified PLGA nanoparticles (NPs) loaded with paclitaxel were constructed by coating the NP surfaces with polydopamine (PD). The average particle size of the produced NPs was 137.6 ± 2.9 nm, with an encapsulation rate of over 80%. In vitro release tests showed that the NPs had pH-responsive drug release properties. Cellular uptake experiments showed that the uptake of modified NPs by tumor cells was significantly better than that of unmodified NPs. A tumor cytotoxicity assay demonstrated that the modified NPs had a lower IC50 and greater cytotoxicity than those of unmodified NPs and commercially available paclitaxel formulations. An in vitro cytotoxicity study indicated good biosafety. A tumor model in female BALB/c rats was established using murine-derived breast cancer 4T1 cells. RGD-modified NPs had the highest tumor-weight suppression rate, which was higher than that of the commercially available formulation. PTX-PD-RGD-NPs can overcome the limitations of antitumor drugs, reduce drug toxicity, and increase efficacy, showing promising potential in cancer therapy.

In-vitro and in-vivo assessment of pH-responsive core–shell nanocarrier system for sequential delivery of methotrexate and 5-fluorouracil for the treatment of breast cancer

Breast cancer (BC) is one of the leading fatal diseases affecting females worldwide. Despite the presence of tremendous chemotherapeutic agents, the resistance emergence directs the recent research towards synergistic drugs’ combination along with encapsulation inside biocompatible smart nanocarriers. Methotrexate (MTX) and 5-fluorouracil (Fu) are effective against BC and have sequential synergistic activity. In this study, a core–shell nanocarrier composed of mesoporous silica nanoparticles (MSN) as the core and zeolitic imidazolate framework-8 nano metal organic frameworks (ZIF-8 NMOF) as the shell was developed and loaded with Fu and MTX, respectively. The developed nanostructure; Fu-MSN@MTX-NMOF was validated by several characterization techniques and conferred high drugs’ entrapment efficiency (EE%). In-vitro assessment revealed a pH-responsive drug release pattern in the acidic pH where MTX was released followed by Fu. The cytotoxicity evaluation indicated enhanced anticancer effect of the Fu-MSN@MTX-NMOF relative to the free drugs in addition to time-dependent fortified cytotoxic effect due to the sequential drugs’ release. The in-vivo anticancer efficiency was examined using Ehrlich ascites carcinoma (EAC) animal model where the anticancer effect of the developed Fu-MSN@MTX-NMOF was compared to the sequentially administrated free drugs. The results revealed enhanced anti-tumor effect while maintaining the normal functions of the vital organs as the heart, kidney and liver.

Using anti-PD-L1 antibody conjugated gold nanoshelled poly (Lactic-co-glycolic acid) nanocapsules loaded with doxorubicin: A theranostic agent for ultrasound imaging and photothermal/chemo combination therapy of triple negative breast cancer.

Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 μg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.

B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC

BackgroundThe combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC).ResultsIn vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts.ConclusionThis study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

Escherichia coli Nissle 1917-driven microrobots for effective tumor targeted drug delivery and tumor regression.

Potent tumor regression remains challenging due to the lack of effective targeted drug delivery into deep tumors as well as the reduced susceptibility of cancer cells to anticancer agents in hypoxic environments. Bacteria-driven drug-delivery systems are promising carriers in overcoming targeting and diffusion limits that are inaccessible for conventional antitumor drugs. In this study, probiotic facultative anaerobe Escherichia coli Nissle 1917 (EcN) was functionalized and formed self-propelled microrobots to actively deliver therapeutic drug and photosensitizer to the deep hypoxic regions of tumors. Doxorubicin (Dox) was firstly modified with cis-aconityl anhydride (CA) and terminal thiol-decorated hydrazone derivative (Hyd-SH) through dual pH-sensitive amide and imine bonds, respectively. The functionalized CA-Dox-Hyd-SH was further coordinated with photosensitizer gold nanorods (AuNRs) and then conjugated to the surface of EcN. The resulting microrobots (EcN-Dox-Au) inherited the mobility characteristics and bioactivity of native EcN. Upon the irradiation of NIR laser, the microrobots exhibited enhanced tumor accumulation and penetration into the deep hypoxia tumor site. Strikingly, after 21 days of treatment with EcN-Dox-Au formulations, complete tumor regression was achieved without relapse for at least 53 days. This self-propelled strategy utilizing bacteria-driven microrobots provides a promising paradigm for enhancing drug penetration and elevating chemosensitivity, resulting in a superior antitumor effect. STATEMENT OF SIGNIFICANCE: Self-propelled Escherichia coli Nissle 1917 (EcN) - mediated microrobots are functionalized to co-deliver therapeutic drugs and photosensitizers to the deep tumor site. Anti-tumor drug doxorubicin (Dox) was modified through dual pH-sensitive bonds on both terminals and then linked with EcN and photosensitizer gold nanorods (AuNRs) to realize tumor microenvironment acidic pH-responsive drug release. Upon irradiation with a NIR laser near the tumor site, AuNRs produced a photothermal effect which realized the superficial tumor thermal ablation and increased the permeability of the tumor cell membrane to facilitate the penetration of microrobots. Moreover, the deep penetration of microrobots also enhanced the susceptibility of the cancer cells to Dox, and realized the complete tumor regression in the established breast cancer-bearing mice without recurrence using a lower dose of drug regimen.

Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease.

The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.

Three-Dimensional Printing Multi-Drug Delivery Core/Shell Fiber Systems with Designed Release Capability.

A hydrogel system with the ability to control the delivery of multiple drugs has gained increasing interest for localized disease treatment and tissue engineering applications. In this study, a triple-drug-loaded model based on a core/shell fiber system (CFS) was fabricated through the co-axial 3D printing of hydrogel inks. A CFS with drug 1 loaded in the core, drug 2 in the shell part, and drug 3 in the hollow channel of the CFS was printed on a rotating collector using a co-axial nozzle. Doxorubicin (DOX), as the model drug, was selected to load in the core, with the shell and channel part of the CFS represented as drugs 1, 2, and 3, respectively. Drug 2 achieved the fastest release, while drug 3 showed the slowest release, which indicated that the three types of drugs printed on the CFS spatially can achieve sequential triple-drug release. Moreover, the release rate and sustained duration of each drug could be controlled by the unique core/shell helical structure, the concentration of alginate gels, the cross-linking density, the size and number of the open orifices in the fibers, and the CFS. Additionally, a near-infrared (NIR) laser or pH-responsive drug release could also be realized by introducing photo-thermal materials or a pH-sensitive polymer into this system. Finally, the drug-loaded system showed effective localized cancer therapy in vitro and in vivo. Therefore, this prepared CFS showed the potential application for disease treatment and tissue engineering by sequential- or stimulus-responsively releasing multi-drugs.

Encapsulating Naringenin in biomimetic proteolipid vesicles abrogates cancer metastasis by targeting apoptotic signaling axis

Naringenin (NG) belongs to the class of flavanones having impressive pharmacological properties. Unfortunately, the in vivo bioavailability of NG is very low due to its higher hydrophobicity, which limits its practical use. Thus, in this study, we tried to develop NG-loaded macrophage membrane-coated liposome-based biomimetic nanoparticles with distinct physicochemical compositions and biological attributes for improving their bioavailability at the target site. The developed biomimetic nanoparticle (BNP) has shown good biocompatibility, stability, satisfactory particle size, pH-responsive drug (NG) release kinetics, and higher cellular uptake in vitro. The anti-metastatic efficacy of NGBNP has confirmed in syngeneic athymic BALB/c nude experimental models. By western blot analysis, semi-quantitative PCR, real-time PCR, and IHC, we conclude that NGBNP gets localized on the metastatic niche via its surface receptor α4, β1 integrin, and VCAM1 of metastatic cells and reduces the number of metastatic colonies in the lungs via regulating the apoptotic signaling axis.

A pH-responsive bi-MIL-88B MOF coated with folic acid-conjugated chitosan as a promising nanocarrier for targeted drug delivery of 5-Fluorouracil.

Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.

Core-shell iron oxide-platinium@metal organic framework/epirubicin nanospheres: Synthesis, characterization and anti-breast cancer activity

Potential cancer therapy can be accomplished by utilizing nano-based platforms that supply facilitated drug penetration inside cancer cells. In this paper, an intelligent therapeutic nano-based system derived from metal–organic framework (MOF) core–shell hybrids with the capacity of potential drug loading, tumor microenvironment-triggered drug release as well as promising cell penetration was developed. The core–shell iron oxide-platinium@MOF/epirubicin (Fe3O4-Pt@MOF/EPI) nanospheres were constructed, where these nanoplatforms endow the system with the capability of pH-responsive drug release. The synthesized Fe3O4-Pt@MOF/EPI nanoparticles were characterized using different well-known techniques. The Fe3O4-Pt@MOF/EPI nanospheres were shown to have a dried size of around 50 nm (evidenced by SEM analysis), a spherical/core–shell/porous structure (evidenced by TEM), and an average hydrodynamic size of 92.89 nm (evidenced by DLS). Additionally, TGA analysis revealed that Fe3O4-Pt@MOF/EPI nanospheres had a weight loss at temperatures between 220 and 450 °C associated with the removal of MOF and EPI from the structure of core–shell nanospheres. The N2 adsorption–desorption data also reflected the porosity of core–shell Fe3O4-Pt@MOF nanospheres by indicating type IV behavior with an apparent hysteresis loop in the range of 0.38–0.98. Furthermore, XRD analysis disclosed the changes in the peak intensity at positions of 57.2° and 39.5°, which indicated the effects of loaded MOF on Fe3O4-Pt nanosphere. Moreover, core–shell Fe3O4-Pt@MOF/EPI nanospheres showed high loading capacity and drug release in a pH-responsive manner. Cell viability and cellular uptake assays on mouse fibroblast (NIH3T3) and triple-negative 4 T1 breast (TNFB) tumors showed that the core–shell Fe3O4-Pt@MOF/EPI nanospheres effectively inhibited TNFB cancer cells proliferation through inducing higher cell penetration compared to free EPI while having good biocompatibility against NIH3T3 cells. In conclusion, the present study may provide useful information about the development of efficient anticancer platforms against breast cancer cells, while further in vivo and pre-clinical assays are required to support this study.

3D printed pH-responsive tablets containing N-acetylglucosamine-loaded methylcellulose hydrogel for colon drug delivery applications

The pH-responsive drug release approach in combination with three-dimensional (3D) printing for colon-specific oral drug administration can address the limitations of current treatments such as orally administered solid tablets. Such existing treatments fail to effectively deliver the right drug dosage to the colon. In order to achieve targeted drug release profiles, this work aimed at designing and producing 3D printed tablet shells using Eudragit® FS100 and polylactic acid (PLA) where the core was filled with 100 µl of N-acetylglucosamine (GlcNAc)-loaded methyl cellulose (MC) hydrogel. To meet the requirements of such tablets, the effects of polymer blending ratios and MC concentrations on physical, thermal, and material properties of various components of the tablets and most importantly in vitro drug release kinetics were investigated. The tablets with 80/20 wt% of Eudragit® FS100/PLA and the drug-loaded hydrogel with 30 mg/ml GlcNAc and 3% w/v MC showed the most promising results having the best printability, processability, and drug release kinetics besides being non-cytotoxic. Manufacturing of these tablets will be the first milestone in shifting from the conventional “one size fits all” approach to personalized medicine where different dosages and various combinations of drugs can be effectively delivered to the inflammation site.

Combining emulsion electrospinning with surface functionalization to fabricate multistructural PLA/CS@ZIF-8 nanofiber membranes toward pH-responsive dual drug delivery

Developing of the multifunctional polymeric carrier for controlled drug release is still one of most challenging task. In this work, a pH-responsive dual drug delivery system was designed and prepared based on the zeolitic imidazolate framework-8 (ZIF-8). The poly(lactic acid)/chitosan (PLA/CS) core-shell nanofiber membranes by emulsion electrospinning, which the hydrophilic drug (Astragalus Polysacharin, APS) was encapsulated in the CS core and the hydrophobic drug (Camptothecin, CPT) was loaded into the PLA shell, respectively. Subsequently, ZIF-8 nanoparticles served as the protective layer were immobilized on the surface of PLA/CS to form multi-structural PLA/CS@ZIF-8 nanofiber membranes. In vitro drug release of nanofiber membranes were studied in the acidic and neutral medium, respectively. The results were that the hydrophilicity and surface roughness of nanofiber membranes rose with increasing of 2-MIM concentrations. The nanofiber membranes also had excellent pH-responsive and controlled release property. Furthermore, the drug release of PLA/CS@ZIF-8 for either APS or CPT were all carried out in a coexisting manner of diffusion and skeleton corrosion. In addition, in vitro cytotoxicity assay indicated nanofiber membranes with good cytocompatibility. Therefore, the multi-structured PLA/CS@ZIF-8 nanofiber membranes has been used as a potential pH-responsive dual drug release system.

Polyamidoamine-stabilized and hyaluronic acid-functionalized gold nanoparticles for cancer therapy

Gold nanoparticles (AuNPs) are versatile nanomaterials that can be used as drug delivery systems and photothermal agents for cancer therapy. In this study, we developed a novel nanoplatform based on AuNPs using a modified one-pot chemical method for the synthesis of AuNPs using generation 3.0 highly branched biphasic polymeric (polyamidoamine) dendrimers as reducing and stabilizing agent, and hyaluronic acid (HA) as functional moiety. Tetrahydrocurcumin (THC) was chosen for this formulation to be encapsulated in the synthesized AuNPs and their efficacy as nanotherapeutics was investigated in vitro. The developed nanoplatform was characterized by various techniques and evaluated for its drug loading and release, cellular uptake, and cytotoxicity on Caco-2 cells. We found that the nanoplatform had optimal size, charge, stability, and solubility, and showed high encapsulation efficiency of THC. The nanoplatform exhibited pH-responsive drug release and enhanced cellular uptake of THC. The nanoplatform also induced apoptosis in Caco-2 cell line. The HA coating on the nanoplatform improved its biocompatibility and specificity, by facilitating its targeting to CD44 glycoprotein on Caco-2 cells. Our results suggest that the developed nanoplatform is a promising nanotherapeutic strategy for cancer therapy by co-delivering of anti-cancer agents and AuNPs to cancer cells.

A novel pH-responsive hydrogel system based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential candidate for controlled drug delivery

pH-responsive hydrogels have become effective and attractive materials for the controlled release of drugs at pre-determined destinations. In the present study, a novel hydrogel system based on Prunus armeniaca gum (PAG) and acrylic acid (AA) was prepared by a free radical mechanism using N, N-methylene bisacrylamide (MBA) as cross-linker and potassium persulfate (KPS) as initiator. A series of hydrogels varying PAG, AA, and MBA concentration was developed to determine the impact of these components. Formulated hydrogels were characterized for pH-responsive swelling, drug release, gel content, and porosity. Structural analysis was performed by FTIR, XRD, and SEM analysis. TGA study was applied to assess thermal stability. Oral acute toxicity and in vivo drug release were performed in rabbits. Hydrogels exhibited pH-dependent swelling and drug release. Swelling, drug loading and release, and porosity increased by increasing PAG and AA concentration while decreased by increasing MBA. The gel content of formulations was increased by increasing all three components. FTIR studies confirmed the development of copolymeric networks and the loading of drug. XRD studies revealed that hydrogels were amorphous, and the crystalline drug was changed into an amorphous form during loading. TGA results indicated that hydrogels were stable up to 600 °C. Acute oral toxicity results confirm that hydrogels were nontoxic up to a dose of 2 g/kg body weight in rabbits. The pharmacokinetic evaluation revealed that hydrogels prolonged the availability of the drug and the peak plasma concentration of the drug was obtained in 6 h as compared to the oral solution of the drug. Tramadol hydrochloride (THC) was used as a model drug. Hence, pH-responsive swelling and release, nontoxic nature and improved pharmacokinetics support that PAG-based hydrogels may be considered as potential controlled-release polymeric carriers.