Controlled Drug Release Properties Research Articles

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Synthesis of ZIF-8/PVA microspheres with the assistance of a microfluidic device and their controlled drug release properties

ZIF-8/PVA microspheres with an even size were synthesized with the assistance of a simple microfluidic device. The ZIF-8/PVA microdroplets were first generated in a simple co-flow microfluidic device using a PVA aqueous solution dispersed with ZIF-8 nanoparticles as the dispersed phase and fatty acid methyl ester (FAME) as the continuous phase. Subsequently, the ZIF-8/PVA microdroplets were further extracted to form ZIF-8/PVA microspheres. The influence of the type of continuous phase on the sphericity of microspheres was investigated and the effect of ZIF-8 content was studied. Further studies showed that decreasing the extraction rate and using additives of NaCl in the dispersed phase could improve the sphericity of the ZIF-8/PVA microspheres. Finally, the synthesized ZIF-8/PVA microspheres were used to study the loading and release of tetracycline. The results showed that the loading of ZIF-8/PVA microspheres was more than 5 times higher than that of pure PVA microspheres. The drug release time of ZIF-8/PVA microspheres was much longer than that of the PVA microspheres and the release rate was significantly affected by the pH of the environment.

Design, fabrication, and evaluation of keratin and pectin incorporated supramolecular structured zero-oxidation state selenium nanogel blended 3D printed transdermal patch

This study investigates the synthesis of selenium nanoparticles (SeNPs), owing to the low cost and abundance of selenium. However, the toxicity of SeNP prompts the development of a selenium nanocomposite (SeNC) containing pectin, keratin, and ferulic acid to improve the bioactivity of Se[0]. Further, incorporating the SeNC in a suitable formulation for drug delivery as a transdermal patch was worth studying. Accordingly, various analytical techniques were used to characterize the SeNPs and the SeNC, confirming successful synthesis and encapsulation. The SeNC exhibited notable particle size of 448.2 ± 50.2 nm, high encapsulation efficiency (98.90 % ± 2.4 %), 28.1 ± 0.45 drug loading, and sustained drug release at pH 5.5. Zeta potential and XPS confirmed the zero-oxidation state. The supramolecular structure was evident from spectral analysis endorsing the semi-crystalline nature of the SeNC and SEM images showcasing flower-shaped structures. Further, the SeNC demonstrated sustained drug release (approx. 22 % at 48 h) and wound-healing potential in L929 fibroblast cells. Subsequently, the SeNC loaded into a gelling agent exhibited shear thinning properties and improved drug release by nearly 58 %. A 3D printed reservoir-type transdermal patch was developed utilizing the SeNC-loaded gel, surpassing commercially available patches in characteristics such as % moisture uptake, tensile strength, and hydrophobicity. The patch, evaluated through permeation studies and CAM assay, exhibited controlled drug release and angiogenic properties for enhanced wound healing. The study concludes that this patch can serve as a smart dressing with tailored functionality for different wound stages, offering a promising novel drug delivery system for wound healing.

Preparation and in vitro evaluation of BBG-250 loaded liposomal formulation for anticancer potential

BackgroundLiposome-mediated drug delivery systems have emerged as a promising avenue for enhancing cancer treatment strategies. This study aims to develop and assess liposomal carriers loaded with Brilliant Blue G-250 (BBG-250), a potent P2X7 receptor antagonist that shows potential as an anti-tumor agent. Specifically, two types of liposomal formulations were designed: conventional liposomes composed of hydrogenated soya phosphatidylcholine (HSPC) and cholesterol, and pH-sensitive liposomes consisting of dioleoylphosphatidylethanolamine (DOPE), distearoylphosphatidylethanolamine-methoxy polyethylene glycol (DSPE-mPEG), dipalmitoylphosphatidylcholine (DPPC), and cholesterol. The investigation focuses on understanding the morphological characteristics, size, stability, drug incorporation efficiency, drug release profiles, blood compatibility, and cytotoxicity of these liposomal formulations.ResultsAdvanced photon correlation spectroscopy using the Nano Plus-3 instrument was employed to evaluate the liposomes. The optimized conventional liposomes (HSPC-cholesterol ratio 7:3) exhibited a size of 125 ± 0.3 nm with a polydispersity index (PDI) of 0.21, indicating uniformity. The pH-sensitive liposomes (DOPE:DPPC:DSPE-PEG2000: Cholesterol 4:3:3:0.3) demonstrated a size of 118 ± 1.2 nm with a PDI of 0.230. Zeta potential measurements confirmed the stability of both formulations under physiological conditions, with values of − 16.93 mV for conventional liposomes and − 25.21 mV for pH-sensitive liposomes. Higher drug-to-lipid ratios were found to enhance drug incorporation efficiency. pH-sensitive liposomes exhibited superior drug release characteristics, with 95% release over 24 h, compared to conventional liposomes, which released 70% of the drug. Blood compatibility assessments revealed the safety of both formulations for intravenous administration. Cytotoxicity studies conducted on A549 cell lines demonstrated the cytocompatibility of both liposomal types across a range of concentrations, with IC50 values surpassing those of the reference drug, docetaxel.ConclusionsThis study underscores the potential of liposomal carriers as effective vehicles for delivering BBG-250, highlighting their stability, biocompatibility, and controlled drug release properties. Despite being slightly less potent than the reference drug, docetaxel, these liposomal formulations hold promise for advancing anticancer strategies. The findings contribute to the evolving landscape of innovative cancer therapy drug delivery systems, offering a novel approach to improving treatment outcomes for cancer patients. The successful development and evaluation of these liposomal carriers pave the way for further investigations and potential clinical applications in the field of cancer therapeutics.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Microfluidic Preparation of pH-Responsive Microsphere Fibers and Their Controlled Drug Release Properties.

In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer (p(BMA-co-DAMA-co-MMA)) solution were introduced into the device for the preparation of hydrogel fibers loaded with polymer microspheres. The structure of the microsphere fiber, including the size and spacing of the microspheres, could be controlled by flow rate, and the microspheres were able to degrade and release cargo responding to acidic pH conditions. By modification with carboxymethylcellulose (CMC), alginate hydrogel exhibited enhanced pH sensitivity (shrunk in acidic while swollen in basic condition). This led to an impact on the diffusion rate of the molecules released from the inner microspheres. The microsphere fiber showed dramatic and negligible degradation and drug release in tumor cell (i.e., A431 and A549 cells) and normal cell environments, respectively. These results indicated that the microsphere fiber prepared in this study showed selective drug release in acidic environments, such as tumor and inflammation sites, which could be applied as a smart surgical dressing with normal tissue protective properties.

Biomimetic nanoparticles to enhance the reverse cholesterol transport for selectively inhibiting development into foam cell in atherosclerosis

A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion “recruitment” properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized “homing” target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized β-cyclodextrin (β-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE−/− mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.Graphical

Fabrication of pH-Responsive Chitosan/Polyvinylpyrrolidone Hydrogels for Controlled Release of Metronidazole and Antibacterial Properties

This research focused on preparing hydrogels with controlled drug release properties to control gastrointestinal tract bacterial infection. Chitosan (CS) and polyvinylpyrrolidone (PVP) were used as the base polymers, with the CS component crosslinked by glutaraldehyde for hydrogel preparation using the solution casting technique. The effect of varying glutaraldehyde content in the hydrogels was characterized by the extent of swelling in simulated physiological fluids of pH 1.2, 6.8, and 7.4; the development of porosity; and gel fraction. Functional groups and covalent and hydrogen bonds formed, thermal stability, phase structure, and morphology were characterized by Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. The results show that the components in the hydrogels have good compatibility and formed honeycomb-like structures. In vitro studies confirmed that the hydrogels have good biodegradability at pH 7.4. Based on these properties, a CS/PVP hydrogel of the ratio of 60 : 40 crosslinked with 600 μL glutaraldehyde was selected for the in-situ loading of 200 mg of the drug metronidazole (MTZ). The hydrogel was characterized for cumulative drug release in the simulated physiological fluids and drug release kinetics using different models and for its antibacterial activity. The best-fit Korsmeyer–Peppas model suggests that MTZ release followed diffusion and swelling-controlled time-dependent non-Fickian transport related to hydrogel erosion. This hydrogel displays enhanced antimicrobial activity against Staphylococcus aureus, and Escherichia coli showed substantial inhibition zones indicating the produced CS/PVP hydrogels are promising candidates for controlled drug release applications.

Clinical Translation of Long-Acting Drug Delivery Systems for Posterior Capsule Opacification Prophylaxis.

Posterior capsule opacification (PCO) remains the most common cause of vision loss post cataract surgery. The clinical management of PCO formation is limited to either physical impedance of residual lens epithelial cells (LECs) by implantation of specially designed intraocular lenses (IOL) or laser ablation of the opaque posterior capsular tissues; however, these strategies cannot fully eradicate PCO and are associated with other ocular complications. In this review, we critically appraise recent advances in conventional and nanotechnology-based drug delivery approaches to PCO prophylaxis. We focus on long-acting dosage forms, including drug-eluting IOL, injectable hydrogels, nanoparticles and implants, highlighting analysis of their controlled drug-release properties (e.g., release duration, maximum drug release, drug-release half-life). The rational design of drug delivery systems by considering the intraocular environment, issues of initial burst release, drug loading content, delivery of drug combination and long-term ocular safety holds promise for the development of safe and effective pharmacological applications in anti-PCO therapies.

Preparation of reversible cross-linked amphiphilic polymeric micelles with pH-responsive behavior for smart drug delivery.

A new type of reversible cross-linked and pH-responsive polymeric micelle (PM), poly[polyethylene glycol methacrylate-co-2-(acetoacetoxy)ethyl methacrylate]-b-poly [2-(dimethylamino)ethyl methacrylate] [P(PEGMA-co-AEMA)-b-PDMAEMA], was synthesized for targeted delivery of curcumin. After reversible cross-linking of the micellar shell, the PMs with a typical core-shell structure exhibited excellent stability against extensive dilution and good reversibility of pH-responsiveness in solutions with different pH values. P(PEGMA9-co-AEMA6)-b-PDMAEMA10 has the lowest critical micelle concentration (CMC) value (0.0041 mg mL-1), the highest loading capacity (13.86%) and entrapment efficiency (97.03%). A slow sustained drug release at pH 7.4 with 12.36% in 108 h, while a fast release (42.36%) was observed at pH 5.0. Furthermore, a dissipative particle dynamics (DPD) simulation method was employed to investigate the self-assembly process and pH-responsive behavior of PMs. The optimal drug-carrier ratio (2%) and fraction of water (92%) were confirmed by analyzing the drug distribution and morphology of micelles during the self-assembly process of the block copolymer. The simulation results were consistent with experimental results, indicating DPD simulation shows potential to study the structure properties of reversible cross-linked micelles. The present findings provide a new method for the development of SDDS with good structural stability and controlled drug release properties.

A pH-responsive chiral mesoporous silica nanoparticles for delivery of doxorubicin in tumor-targeted therapy

The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores, prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that DOX@CS-CMSN was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo. Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy.

Mesoporous biophotonic carbon spheres with tunable curvature for intelligent drug delivery

Abstract Mesoporous carbon spheres (MCSs) are widely used in the field of pollutants adsorption, energy storage and various biomedicine applications such as targeted delivery vector, phototherapy sensitizers, bioimaging contrast agents, etc. Current synthetic strategies including soft templating and hard templating methods generally have the limits of using expensive surfactants or lack of control over the pore structures. Therefore, the complex and uncontrollable pore structures limit its further clinical application. Herein, we proposed a new synthetic strategy to control the uniformity of pore channel arrangement in MCSs which can modulate the photonic property and the corresponding light controlled drug release property in intelligent drug delivery. The as obtained MCSs with relative uniform pore channel arrangement and long pore channels are demonstrated to have the best NIR light-induced drug release performance. This work provides not only new synthetic method to modulate pore structure characteristics and biophotonic property of MCSs, but also uniform MCSs as novel delivery platforms with advanced controlled release performance.

PH-redox responsive cascade-targeted liposomes to intelligently deliver doxorubicin prodrugs and lonidamine for glioma

To synergistically treat glioma with a combination chemotherapy, we design and prepare novel cascade-targeted liposomes (Lip-TPGS) using glucose and triphenylphosphonium (TPP) as targeting moieties, which could intelligently deliver redox-sensitive doxorubicin (DOX) prodrugs (SDOX) and chemotherapeutic sensitizer lonidamine (LND). The pH-responsive ligand Chol-TPG modified by PEGylated glucose can overcome the blood-brain barrier and reach tumor cells. Combined with the modification of mitochondria targeting ligand (Chol-TPP), Lip-TPGS are endowed with pH-responsive charge regulation function and multi-stage targeting abilities. After triggered by the excessive glutathione in tumor cells, Lip-TPGS could sufficiently release the parent drugs DOX, which would significantly reduce side effects without compromising anti-glioma efficacy. Therefore, Lip-TPGS possess these characteristics: good pharmacokinetic behavior, superior brain targeting ability, specific tumor recognition and internalization capability, and strong endo/lysosome escaping and mitochondria targeting potential. Furthermore, Lip-TPGS exhibit significant advantages on anti-glioma by inhibiting proliferation, promoting apoptosis, inducing mitochondria dysfunction, inhibiting migration and invasion, prolonging the survival time, narrowing tumor areas, limiting lung metastasis, and reducing toxicity to normal organs. In summary, Lip-TPGS, with cascade targeting abilities from tissue/cell to organelle levels and highly controlled drug release properties, would become a promising drug delivery system for glioma treatment.

Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

Preparation of a "Branch-Fruit" structure chitosan nanofiber physical hydrogels with high mechanical strength and pH-responsive controlled drug release properties.

The poor mechanical properties of chitosan physical hydrogels seriously hinder their application in the biomedical field. Inspired by the structure of cell tissues, a novel chitosan nanofiber (CSNF)/Hyaluronic acid (HA)/β-glycerophosphate disodium (β-GP) drug-loaded hydrogel was prepared by micro-dissolution and physical crosslinking. The hydrogel has a “Branch-Fruit” structure and exhibits excellent mechanical properties, good biocompatibility and cell-adhesion properties. Human cancer cells (HeLa) can adhere to the hydrogel surface, which might facilitate tumor site-specific administration of drugs. This material also exhibits high pH sensitivity, with which drug release can be triggered under acidic conditions at pH 4.00. The mechanical strength and drug release behavior of this hydrogel can be easily adjusted by varying the CSNF content.

Microfluidic-Generated Immunomodulatory Nanoparticles and Formulation-Dependent Effects on Lipopolysaccharide-Induced Macrophage Inflammation.

Nanoparticles (NPs) have emerged as a highly useful and clinically translatable drug delivery platform for vast therapeutic payloads. Through the precise tuning of their physicochemical properties, NPs can be engineered to exhibit controlled drug release properties, enhanced circulation times, improved cellular uptake and targeting, and reduced toxicity profiles. Conventional bulk methods for the production of polymeric NPs suffer from the ability to control their size and polydispersity, batch-to-batch variability, significant preparation times, and low recovery. Here, we describe the development and optimization of a high-throughput microfluidic method to produce cargo-less immunomodulatory nanoparticles (iNPs) and their formulation-dependent anti-inflammatory properties for the modulation of lipopolysaccharide (LPS)-induced macrophage responses. Using poly(lactic acid) (PLA) as the core-forming polymer, a rapid and tunable microfluidic hydrodynamic flow-focusing method was developed and optimized to systematically evaluate the role of polymer and surfactant concentration, surfactant chemistry, and flow rate ratio (FRR) on the formation of iNPs. A set of iNPs with 6 different surface chemistries and 2 FRRs was then prepared to evaluate their inherent anti-inflammatory effects using bone marrow-derived macrophages stimulated with the Toll-like receptor 4 agonist, LPS. Finally, a lyophilization study was performed using various cryoprotectants and combinations to identify preferable conditions for iNP storage. Overall, we demonstrate a highly controlled and reproducible method for the formulation of iNPs using microfluidics and their formulation-dependent inherent anti-inflammatory immunomodulatory properties, which represents a potentially promising strategy for the management of inflammation.

Stimuli-Responsive Polymeric Nanosystems for Controlled Drug Delivery

Biocompatible nanosystems based on polymeric materials are promising drug delivery nanocarrier candidates for antitumor therapy. However, the efficacy is unsatisfying due to nonspecific accumulation and drug release of the nanoparticles in normal tissue. Recently, the nanosystems that can be triggered by tumor-specific stimuli have drawn great interest for drug delivery applications due to their controllable drug release properties. In this review, various polymers and external stimuli that can be employed to develop stimuli-responsive polymeric nanosystems are discussed, and finally, we delineate the challenges in designing this kind of Nanomedicine to improve the therapeutic efficacy.

Recent advances in polymer shell oily-core nanocapsules for drug-delivery applications.

Polymeric nanocapsules are vesicular drug-delivery systems composed of an inner oily reservoir surrounded by polymeric membranes. Nanocapsules have various advantages over other nanovesicular systems such as providing controlled drug release properties. We discuss the recent advances in polymeric shell oily-core nanocapsules, illustrating the different types of polymers used and their implementation. Nanocapsules can be utilized for many purposes, especially encapsulation of highly lipophilic drugs. They have been shown to have variable applications, especially in cancer therapy, due to the ability of the polymeric shell to direct the loaded drugs to their target sites, as well as their high internalization efficacy. Those productive applications guaranteed their high potential as drug-delivery systems. However, their clinical development is still in an early stage.

Shape memory polyacrylamide/gelatin hydrogel with controllable mechanical and drug release properties potential for wound dressing application

In this work, various shape memory polyacrylamide/gelatin (PAM-Gels) hydrogels with interpenetrating double networks were synthesized via a facile one-pot method. Taking advantage of the thermal reversible property of physical gelatin network and the constant of chemical crosslinking polyacrylamide network, the prepared PAM-Gels hydrogels showed shape memory function under warm water. Moreover, the shape memory, mechanical, drug release, and swelling properties of the prepared PAM-Gels hydrogels could be tuned by altering the gelatin component content. Notably, the PAM-Gel5 hydrogel containing 5% w/v of gelatin exhibited the most effective enhancements in physicochemical properties, and the highest shape fixity and shape recovery rate were 78.2% and 93.5%, respectively. Meanwhile, it could retain the integrity of its shape even with high water uptake. More importantly, the PAM-Gel5 hydrogel possessed well balanced mechanical properties (e.g. tensile strength was 0.57 MPa and elongation at break was 1556% in tensile test; compression stress was 0.06 MPa and Young's modulus was 0.38 MPa in compression test) among the as-prepared PAM-Gels hydrogels, due to its uniform pore size distribution and smaller pore size. Furthermore, the drug release experiment revealed that the PAM-Gel5 hydrogel showed sustained release characteristics, and the majority of loaded model drug could be released within 24 h under physiological conditions. Additionally, cytotoxicity test suggested the representative PAM-Gel5 hydrogel exhibited good in vitro cytocompatibility. This work provides a viable avenue for developing bio-compatible shape memory hydrogel with acceptable mechanical and drug release properties applied as wound dressing.

Fabrication and bioactivity evaluation of curcumin and paclitaxel loaded lipid nanoparticles of pH-sensitive histidinylated cationic amphiphile

Drug resistance, inefficient cellular uptake and the subservient drug release to increase the intracellular drug concentration inside the tumor cells are the key reasons for low therapeutic efficacy of drug-loaded lipid nanoparticles in cancer therapy. Herein, we report on the design, synthesis and bioactivity evaluation of Curcumin & Paclitaxel (PTX) encapsulated endosomal pH-Sensitive lipid nanoparticles of histidinylated cationic amphiphile (16-GH; 2 in 1 system) to overcome these challenges. Findings in fluorescence resonance energy transfer (FRET) assay and in vitro drug release studies showed a controlled pH dependent fusogenic and drug release properties of the lipid nanoparticles of cationic amphiphile 16-GH respectively. Further in vitro studies revealed that Curcumin & PTX encapsulated nanoparticles of lipid 16-GH significantly inhibited proliferation of tumor cells than healthy cells. These lipid nanoparticles were further analyzed for their effect on 5-bromo-2'-deoxyuridine (BrdU) incorporation, Annexin V-FITC and cell cycle arrest (Sub-G1 phase). Further studies also confirmed that nanoparticles of lipid 16-GH containing Curcumin & PTX displayed significantly enhanced the caspase3/9 activity. Remarkably, nanoparticles of lipid 16-GH containing Curcumin & PTX are efficient in inducing apoptosis. The results in our initial mechanistic studies support the notion that the tumor cell selective cytotoxic capability of the lipid nanoparticles of the presently described endosomal pH-sensitive lipid probably instigates from depolarization of mitochondrial membrane potential and subsequent activation of caspases 3 and 9. The distinguishing feature of the currently described endosomal pH-sensitive system is that it not only efficiently delivers highly potent anti-cancer agents (Curcumin & PTX) to tumor cells, but the lipid nanoparticle drug carrier itself also contributes to inhibiting tumor cell growth. In summary, the presently described lipid nanoparticles are expected to simultaneously delivering combination of drugs to various types of tumor models.