pH-dependent Release Research Articles

Enhanced antitumor activity of lapatinib against triple-negative breast cancer via loading in human serum albumin

Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature. Human serum albumin (HSA) is a promising drug delivery platform, offering high binding capacity, biocompatibility, and reduced toxicity. Lapatinib (LAP), a tyrosine kinase inhibitor for TNBC, is hindered by poor water solubility and toxicity. To address these issues, LAP was encapsulated within HSA (HSA-LAP), and its structural, drug release, and therapeutic properties were evaluated in cellular and animal TNBC models. HSA-LAP demonstrated efficient drug loading and pH-dependent tumor-targeted release, favoring acidic tumor microenvironments. Structural and microscopic studies confirmed LAP binding to HSA, with only minor structural and no significant morphological changes observed. In 4 T1 breast cancer cells, HSA-LAP exhibited superior anti-proliferative, pro-apoptotic, and anti-migratory effects compared to free LAP, which were further amplified when combined with VGB3, a VEGFR1/2-targeting peptide, indicating an effective dual-targeting strategy for TNBC. In vivo, HSA-LAP showed greater tumor inhibition and improved survival rates, especially in combination with VGB3 through apoptosis induction. Biodistribution studies using technetium-99 m (99mTc) labeling revealed enhanced tumor targeting. These findings highlight the potential of HSA as a delivery vehicle for LAP, particularly in combination with anti-angiogenic agents like VGB3, offering a promising therapeutic strategy for TNBC.

Radiation-induced nanogel engineering based on pectin for pH-responsive rutin delivery for cancer treatment.

This research investigates the formulation of a nanogel complex using pectin and poly(acrylic acid) (PAAc) to encapsulate rutin. The nanogel's pH-responsive behavior and its potential as a targeted drug delivery platform are investigated. The gamma irradiation-induced crosslinking mechanism is elucidated, highlighting its role in creating a stable three-dimensional network structure within the polymer matrix. Fourier transform infrared spectroscopy analysis sheds light on the molecular interactions within rutin and the nanogel-rutin complex. The pH-responsive behavior of the nanogel is explored, showcasing its ability to release rutin selectively in response to pH variations and displaying high physical and chemical stability. Transmission electron microscopy imaging provides visual insights into nanogel morphology and interactions. The cumulative drug content from the nanogel was 86.14 ± 2.61%. The pH-dependent release profile of the nanogel was examined, demonstrating selective rutin release in response to varying pH levels. Cytotoxicity studies were conducted against four human cancer cell lines-HepG2, A549, MCF-7, and HCT-116 showing significant reductions in IC50 values, indicating enhanced therapeutic efficacy. Additionally, molecular docking studies revealed strong binding interactions of rutin with VEGFR-2 and EGFRT790M. Our nanogel compound 5 significantly reduced the IC50 values for HepG2, A549, MCF-7, and HCT-116 cells by 58.19%, 81.29%, 71.81%, and 67.16%, respectively. Furthermore, it lowered the IC50 values for VEGFR-2 and EGFRT790M by 29.66% and 68.18%, respectively.

Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins.

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy.

Ferric ions crosslinked hyaluronic acid beads: potentials for drug delivery use

Introduction and purpose Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads. Methods The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead’s morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated. Results The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model. Conclusions This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Hyperbranched polylysine/oxidized carboxymethyl cellolose integrated gelatin composite for wound treatment

Herein, we report the preparation and evaluation of a new composite consisting of gelatin matrix, oxidized carboxymethyl cellulose (OCMC), and hyperbranched polylysine (PL) components for full-thickness wound treatment. To enhance the antimicrobial activity of the gelatin matrix, OCMC/PL was successfully combined with this matrix via the Schiff base reaction. Moreover, allantoin (Alla) as a drug model was loaded by this composite and the optimal formulation for wound healing (PLOCG-Alla) was obtained. The structural properties, thermal stability, crystallinity and interactions between materials were investigated using SEM, TGA, XRD and FTIR techniques. Cytotoxicity and antibacterial capacity were evaluated by MTT assay and colony counting methods, respectively. The release behavior was investigated at two different pH values. Blood coagulation and wound healing potential were also evaluated in vivo. PLOCG-Alla exhibited high antibacterial capacity, pH-dependent release behavior, biocompatibility and high blood clotting ability. It also accelerated wound healing in vivo.

Locust bean gum-based silver nanocomposite hydrogel as a drug delivery system and an antibacterial agent

Effective drug release is of utmost importance in the medical field for treating various diseases, particularly cancer. Nanocomposite hydrogels remain the best materials for enhancing the bioavailability and therapeutic levels of drugs as they enable sustained, targeted, or controlled drug release. In this work, a nanocomposite hydrogel containing locust bean gum (LBG), poly(4-acryloylmorpholine) (PAcM), and silver nanoparticles (SN) has been made using an eco-friendly microwave (MW)-assisted method and characterized by various advanced techniques. The material is evaluated for its potential as a polymer matrix towards delivering 5-fluorouracil (5-FU), an anticancer drug in the gastrointestinal tract, and inhibiting bacterial growth. The pH-dependency of the nanocomposite material towards swelling and drug release and its antibacterial characteristics have been compared with the neat gel in order to understand the role of SN in enhancing the performance of the materials. The results indicated both polymer materials exhibit a pH-dependent release of 5-FU with a higher release at pH 1.2, simulated gastric fluid, than at pH 7.4, simulated intestinal fluid. About 72 % of the loaded drug was released from the nanocomposite, as compared to 44 % from the neat gel at pH 1.2 during the observation period of 3 h. The drug release process could be best explained by the first-order kinetic model and Fickian diffusion transport mechanism. The nanocomposite exhibited remarkable antibacterial activity against Staphylococcus aureus and Escherichia coli. The biocompatibility of the drug-loaded nanocomposite was demonstrated by a cytotoxicity study, which showed higher than 80 % viability of healthy IEC-6 cells. The results indicate the suitability of the developed nanocomposite material as a polymer matrix for sustained release of 5-FU for cancer therapy and also as an antibacterial agent to fight against bacterial infections.

Double Encapsulation of Resveratrol and Doxorubicin in Composite Nanogel—An Opportunity to Reduce Cardio- and Neurotoxicity of Doxorubicin

The simultaneous encapsulation of drugs into nanosized delivery systems could be beneficial for cancer therapies since it could alleviate adverse reactions as well as provide synergistic effects. However, the encapsulation of hydrophobic drugs into hydrophilic nanoparticles, such as nanogels, could be challenging. Therefore, innovative technological approaches are needed. In this research, a composite nanogel system was prepared from chitosan, albumin, and hydroxypropyl-β-cyclodextrin for co-delivery of the hydrophilic anticancer drug doxorubicin and hydrophobic antioxidant resveratrol. The nanoparticles were characterized using dynamic light scattering and found to have a hydrodynamic diameter of approx. 31 nm, narrow size distribution (PDI = 0.188), positive ƺ-potential (+51.23 mV), and pH-dependent release of the loaded drugs. FTIR and X-ray analyses proved the successful development of the composite nanogel. Moreover, the double-loaded system showed that the loading of resveratrol exerted protection against doxorubicin-induced toxicity in cardioblast H9c2 and neuroblast SH-SY5Y cells. The simultaneous loading did not influence the cytostatic effect of the antitumor agent in lymphoma L5178Y and L5178MDR cell lines.

Fabrication of gallic acid containing poly(vinyl alcohol)/chitosan electrospun nanofibers with antioxidant and drug delivery properties

Chitosan-based nanofibers with excellent properties are attractive materials for specific industrial applications of contemporary interest. This work aims to fabricate functional nanofibers based on poly(vinyl alcohol)/chitosan (CS) with an antioxidant and model drug molecule, gallic acid (GA), by electrospinning, followed by cross-linking through glutaraldehyde (PVA-CS-GAs). PVA-CS-GAs were electrospun at two different concentrations by the adjustment of the CS feeding ratio. The detailed characteristics of the as-prepared electrospun nanofibers were elucidated by Fourier Transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), water contact angle (WCA) measurements, thermogravimetric and differential scanning calorimetry (TGA and DSC) analyses. SEM images indicated that the average fiber diameter distribution was in the range of 90–110 nm. The results show that morphology, mean diameter, wettability, and thermal characteristics of the composite nanofibers were affected by the CS feeding ratio. Although the increase in the amount of polar -OH groups with the addition of GA caused an improvement in the hydrophilicity and thermal stability of the electrospun nanofibers, it also caused a decrease in the thermal transition temperatures. Furthermore, antioxidant tests based on DPPH radical scavenging ability and in vitro release studies demonstrated that the cross-linked PVA-CS-GA composite nanofibers have good antioxidant activity and a pH-dependent drug release rate, indicating their potential for implementation in wound healing and drug delivery applications.

A pH-Responsive Ti-Based Local Drug Delivery System for Osteosarcoma Therapy.

Osteosarcoma is one of the major bone cancers, especially for youngsters. The current treatment usually requires systemic chemotherapy and the removal of bone tumors. Titanium (Ti)-based implants can be modified as local drug delivery (LDD) systems for controllable and localized chemotherapeutic drug release. In this work, a pH-responsive Ti-based LDD prototype was designed by introducing polydopamine (PDA) to release doxorubicin (DOX) around osteosarcoma cells with low pH. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a contact angle meter were applied for surface characterization. Both direct and indirect cell culture modes were performed for biocompatibility and biofunction assessments. The results indicate that the Ti-based LDD prototype exhibits significant pH-dependent DOX release. The cumulative release can reach up to approximately 40% at pH = 6.0 after 72 h, but only around 20% at pH = 7.4. The Ti-based LDD implant shows good biocompatibility with approximately 93% viability of MC3T3 cells after direct culture in vitro for 24 h. Both direct and indirect culture modes verify the good anti-osteosarcoma function of the LDD implant, which should be attributed to the pH-responsive release of DOX.

Doxorubicin-loaded methoxy-intercalated kaolinite as a repackaging of doxorubicin for an enhanced breast cancer treatment: in vitro and in vivo investigation

Doxorubicin is one of the most common wide-spectrum chemotherapeutics. However, its efficacy is limited due to off-target accumulation and selectivity issues. In this study, we compared the anti-cancer effect and biocompatibility of KaoliniteMeOH-Dox, a doxorubicin repackaging, to doxorubicin monotherapy. The formulation was extensively tested using transmission electron microscopy, dynamic light scattering, zeta potential, Fourier transform infrared, x-ray diffraction, and in vitro drug release. The MTT assay measured MCF-7 cell growth inhibition in vitro. In vivo testing involved 20 naïve mice and 40 Ehrlich solid tumor-inoculated mice. The tumor size was monitored for 18 days. In all experimental groups, tumor and cardiac tissues were evaluated for cytotoxicity and genotoxicity by addressing oxidative stress, histopathology, and comet assay. We found that kaoliniteMeOH-Dox has many advantages in terms of size, charge, shape, high loading efficiency (90.16%), and pH-dependent release. The MTT assay showed that the formulation outperformed doxorubicin in growth inhibition and selectivity. In vivo, research showed that kaoliniteMeOH-Dox suppressed tumors by 86.075% compared to 60.379% for free doxorubicin. Histological analysis showed that kaoliniteMeOH-Dox reduced tumor size, metastasis, and carcinogenic oxidative stress and inflammation in mice without harming naive mice. Based on the obtained data, the kaoliniteMeOH-Dox formulation holds promise for breast cancer treatment and warrants further investigation.

Growth of dendritic CuS nanostructures for photoacoustic image guided Chemo-Photothermal therapy

Herein, we report a unique method for design and development of carboxyl enriched dendritic CuS nanostructures (CuS NSs) for photoacoustic image guided chemo-photothermal therapy. The dendritic network was grown on the surface of CuS nanoparticles via layer-by-layer assembly of amino acid. XRD and TEM studies established the formation of crystalline well-spherical nanosized hexagonal covellite (CuS) phase. The successful growth of dendritic structure was apparent from the rise in surface charge, hydrodynamic diameter and characteristic vibrational band intensity of peptide bonds. The developed different generations of dendritic CuS NSs (D0-CuS NSs, D1-CuS NSs, D2-CuS NSs and D3-CuS NSs) displayed wide-ranging absorption band in near infrared (NIR) zone and exhibited good photothermal heating efficacy upon irradiation of 980 nm laser light. From in-vitro cellular studies, it has been found that the NIR irradiation effectively enhanced the photothermal toxicity of D3-CuS NSs towards cancer cells. Moreover, these negatively charged water-dispersible D3-CuS NSs were conjugated with positively charged anticancer drug, doxorubicin hydrochloride (DOX) through electrostatic interaction. The DOX loaded D3-CuS NSs (DOX@D3-CuS NSs) revealed pH dependent drug release behaviour and their considerable uptake in breast cancer cells (MCF-7). Further, DOX@D3-CuS NSs exhibited a much higher toxicity towards cancer cells upon NIR light over individual counterparts suggesting their strong ability for chemo-photothermal therapy. Moreover, these biocompatible CuS NSs have shown excellent concentration dependent photoacoustic properties at pulse laser excitation (850 nm) and thus, they can be found potential application in chemo-photothermal therapy.

Toward Upconversion (Yb-Er) and near-Infrared (Yb-Ho-Er, Nd-Yb) Thermometry with Sea Urchin Type GdPO4 Nanoarchitectures.

In recent years, optical temperature probes operating in the second near-infrared (BW-II) and third near-infrared (BW-III) biological windows have garnered significant attention in the scientific community. For biological applications these probes offer distinct advantages, including enhanced tissue penetration depth, minimal autofluorescence, and a remarkable improvement in imaging sensitivity and spatial resolution. Moving toward theranostic applications, there is a growing demand for the development of materials that integrate both BW-II and BW-III thermometry systems with drug delivery functionalities. In this study, we concentrate on the development of GdPO4 materials, utilizing both hard and sacrificial template routes to synthesize (hollow) GdPO4 porous sea urchin-like particles. We first investigated the development of a Boltzmann-type thermometer utilizing an Yb-Er upconversion system, designed to operate within the physiological temperature range. Our exploration extends to the potential of GdPO4 particles in near-infrared (NIR) thermometry, spanning the first, second, and third biological windows with systems like Yb-Ho-Er, Nd-Yb, and Ho-Yb, respectively. We further examined the temperature impact of the Yb-Ho-Er system on the NIR emission within a biologically relevant setting, using a phantom that replicates biological tissue. Furthermore, we illustrate the successful loading of these materials with doxorubicin (DOX·HCl), a model anticancer drug, showing these particles exhibit pH-dependent DOX release. This demonstrates the versatility of these materials as upconversion and NIR thermometers while simultaneously serving as an on-demand drug carrier. The investigation involves assessing their cytotoxicity on specific human cells (Normal Human Dermal Fibroblasts (NHDFs)), to determine their viability for potential use in biological applications. The study also investigates how effectively loading the particles with DOX enables targeted delivery to a cellular model of lymphoma (Jurkat E6-1), resulting in cell death. This comprehensive analysis highlights the promising potential of GdPO4 particles for medical applications.

Co-biopolymer of zein/starch hydrogel incorporated montmorillonite for efficient quercetin delivery in lung cancer treatment

Today, cancer treatment is an important issue in the medical world due to the challenges and side effects of ongoing treatment procedures. Targeted nanodrug delivery systems can replace current methods to mitigate such side effects. In this study, a novel nanocomposite of starch, zein, and MMT with the drug quercetin (QC) was synthesised with the aim of effectively killing A549 cancer cells despite reducing any harmful effects on normal cells, and then the effect of the nanosystem to evaluate the damages on L929 cell lines (healthy) and A549 (cancerous) were investigated. For this purpose, the drug release test from the nanosystem was conducted at two pH levels of 5.4 and 7.4, and it was observed that the nanosystem successfully released 29 % of the QC drug in the first 12 h. The prepared nanocomposites were analysed by XRD, FT-IR, FESEM, DLS, Zeta potential, and MTT techniques. It was found that the nanoparticles exhibited a consistent and even morphology, with an average particle size ranging from 50 to 100 nm. The DLS study provided evidence of the precise range of size and outstanding durability of the nanoparticles. The nanosystem exhibited a notable enhancement in the rate of cell death in malignant tumours, as evidenced by the MTT tests. The synthesised nanosystem showed a precise and pH-dependent release of the drug, which indicates the biocompatibility of the nanocarrier for the QC drug. According to this, it has the capacity to function as an acceptable substitute for the therapeutic techniques that are now being used.

Hyaluronic acid-functionalized carboxymethyl dextran-coated melatonin nanoconjugates for targeted etoposide delivery in metastatic colon cancer: Extensive in-vitro investigation in HCT116 cell lines, antimicrobial efficacy, and anti-angiogenic potential in chick chorioallantoic membrane (CAM) assay

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of −29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential.

CYpHER: catalytic extracellular targeted protein degradation with high potency and durable effect

Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell’s protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway. Here we describe CYpHER (CatalYtic pH-dependent Endolysosomal delivery with Recycling) technology with potency and durability from a catalytic mechanism that shares the specificity and straightforward modular design of endolysosomal uptake. By bestowing pH-dependent release on the target engager and using the rapid-cycling transferrin receptor as the uptake receptor, CYpHER induces endolysosomal delivery of surface and extracellular targets while re-using drug, potentially yielding increased potency and reduced off-target tissue exposure risks. The TfR-based approach allows targeting to tumors that overexpress this receptor and offers the potential for transport to the CNS. CYpHER function was demonstrated in vitro with EGFR and PD-L1, and in vivo with EGFR in a model of EGFR-driven non-small cell lung cancer.

High loading and sustained-release system of doxorubicin-carbon dots as nanocarriers for cancer therapeutics

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, dynamic light scattering, Zeta Potential measurements, FTIR, and transmission electron microscopy. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e. -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67 ± 0.36%.In vitrodrug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28% (pH 5), 13.30 ± 0.03% (pH 7.4), and 13.95 ± 0.18% (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CDs uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

Modified Release Interpenetrating Polymeric Network Hydrogel Beads of Montelukast Sodium Via Box Behnken Design

Background: Interpenetrating Polymeric Networks (IPN) are cross-linked polymeric alloys developed when two or more cross-linked polymers inter-penetratingly entangle. Interpenetrating polymeric networks possess several benefits including stability, biocompatibility, biodegradability, high swelling ability, and modified release efficiency. Aim: The aim of this study is to design stable, control-released montelukast sodium-loaded IPN hydrogel beads as a promising approach toward drug delivery. Objective: The goal of the present work was to develop Chitosan (swellable polymer) and glutaraldehyde (cross-linker) based modified (controlled) released montelukast sodium IPN hydrogel beads. Methods: The montelukast sodium IPN hydrogel beads were prepared via the precipitation method, and the final batch of IPN hydrogel beads was based on particle size, percent entrapment efficiency, area of swelling, and cumulative percent drug release using an overlay plot in Box-Behnken design. Compatibility studies (DSC, FT-IR) and microscopical observation (SEM) confirmed the compatibility and sphericity of the formulations. Results: The optimized (comprising 2.01% chitosan and 0.48% glutaraldehyde) IPN hydrogel beads having satisfactory particle size (817.76±54.49 μm), good entrapment efficiency (71.36±3.04%), and area of swelling (27.00±1.68 mm2) showed swelling and pH-dependent controlled montelukast release (92.96±1.05%) after 12 h with longer duration of action. Conclusion: The prepared montelukast sodium IPN hydrogel beads could be a potent control-released drug delivery vehicle.

Co-delivery of novel valsartan and hydrochlorothiazide pH-responsive electrospun polymeric nanofibers for improved oral delivery

Valsartan (VAL) and Hydrochlorothiazide (HCTZ) as a fixed-dose combination are widely used for the management of hypertension. To enhance the dissolution and oral delivery of VAL (BCS class II drug) and HCTZ (BCS class IV drug), nanofibers containing both drugs were prepared using an electrospinning technique. VAL/HCTZ-loaded NFs were prepared using Eudragit L100-55 (EUD L100-55) and Poly (ethyne oxide) (PEO) polymer mixture and the formulation process was optimized through three process variables of polymer composition, polymer concentration, and spinning voltage. VAL/HCTZ-loaded NFs were characterized for their size, surface morphology, entrapment efficiency (%EE), drug-polymer interaction, in vitro drug release, ex-vivo permeation, and in vivo studies. Smooth, beadles and uniform drug-loaded NFs were successfully fabricated using optimum polymer composition (EUD L100-55/PEO 3:1), concentration (12 % w/v), and applied voltage (30 KV). The optimum formula (F9) showed a low average nanosize of 300 nm and a high drug loading of > 90 % was achieved. In vitro, release results showed a pH-dependent drug release, with minimum drug released at pH lower than 4.5, but a significant and complete release of both drugs was achieved at pH 6.5. The EUD L100-55/PEO improved the dissolution of VAL and HCTZ compared to free drugs at the intestinal site of absorption. Differential Scanning calorimetry and Fourier Transform Infra-Red studies showed both drugs’ amorphization and compatibility between drugs and polymers. Permeability behavior for the VAL/HCTZ-loaded NFs was found to be significantly higher than free drug suspensions of both drugs which indicated the improvement of VAL and HCTZ permeability through the intestinal membrane. The in vivo study proved the enhanced oral anti-hypertensive action of drugs-loaded NFs compared to free drug suspensions. The superior in vitro release, ex-vivo permeation, and in vivo anti-hypertensive effect indicate that drug-loaded nanofibers have the potential to improve the biological activity and hence oral delivery of the fixed-drug combination.

A study of the oral bioavailability and biodistribution increase of Nanoencapsulation-driven Delivering radiolabeled anthocyanins

Anthocyanins have antioxidant, anti-inflammatory, and anticancer properties but have limited bioaccessibility and bioavailability due to molecular instability in the gastrointestinal tract. This study evaluated the absorption and biodistribution of free and nanoencapsulated radiolabeled anthocyanin (cyanidin-3-O-glucoside). A new methodology was efficiently developed for radiolabeling anthocyanins with Technetium (99mTc-anthocyanins). Then, the anthocyanins were nanoencapsulated through self-assembly using citrus pectin and lysozyme. The nanostructures have a size of 190 nm, a zeta potential of –30 mV, and an invariably spherical and homogeneous morphology. The biodistribution in different tissues, the kinetics of absorption, and molecular visualization by micro single-photon emission computed tomography/computed tomography (µSPECT/CT) showed that the nanoencapsulated anthocyanins are absorbed differently than free anthocyanin in mice. After oral administration, nanostructured anthocyanins were delivered to the blood, spleen, bladder, pancreas, and bone, unlike unencapsulated anthocyanins found only in kidneys and bladder. In silico data indicated the stabilization between compounds in nanocapsules and demonstrated the pH-dependent release of anthocyanins in the intestine. The nanoencapsulation alters the absorption kinetics, increasing the blood’s bioavailability and the organs’ uptake, suggesting an improvement of the biological effects and potential clinical application.