Drug Loading Behavior Research Articles

Reduction-Responsive Polyprodrug Nanoplatform Based on Curcumin for Tumor-Targeted Therapy.

Polymer prodrug nanoparticles have become an emerging drug delivery system in cancer therapy due to their high drug loading. However, their poor drug release and lack of tumor cell targeting limit their clinical application. This study aimed to prepare targeted and reduction-reactive polyprodrug nanocarriers based on curcumin (CUR) for co-delivery of doxorubicin (DOX), labeled as DOX/HAPCS NPs, and to investigate their anticancer activity. The polymer was synthesized and characterized by chemical method. The drug loading and drug release behavior of DOX and CUR in polymer nanoparticles were determined. Moreover, the antitumor effects of polymer nanoparticles were evaluated using an MTT experiment and tumor inhibition experiment, and the synergistic effect of co-delivered DOX and CUR was explored. The particle size of DOX/HAPCS NPs was 152.5nm, and the potential was about -26.74 mV. The drug-carrying capacity of DOX and CUR was about 7.56% and 34.75%, respectively, indicating high drug-carrying capacity and good stability. DOX and CUR released over 90% within 24 hours in the tumor environment. Compared with free DOX, DOX/HAPCS NPs demonstrated significantly enhanced cell and tumor inhibitory effects (P< 0.05) in vivo and in vitro and changed drug distribution to avoid toxic side effects on normal tissues. The combined index showed that DOX and CUR showed synergistic anticancer effects at a set ratio. The prepared reduction-responsive targeted polymer nanomedical DOX/HAPCS NPs exhibited a synergistic anti-cancer effect, with high drug loading capacity and the ability to release drugs in proportion, making it a promising polymer nanoparticle drug delivery system.

PH and temperature dual-responsive magnetic yolk-shell mesoporous silica nanoparticles for controlled drug delivery

New magnetic yolk-shell mesoporous silica nanoparticles (Fe3O4@V-mSiO2-PNVCL) were prepared by grafting temperature-sensitive amino-terminated poly (N-vinylcaprolactam) (PNVCL-NH2) on the surface of aldehyde-functionalized magnetic mesoporous silica nanoparticles (Fe3O4@V-mSiO2-CHO) through a Schiff base reaction. Various characterizations were used to confirm the structures, and the drug loading and release behaviors were studied. The drug loading was achieved as PNVCL stretched at room temperature and the drug loading content was up to 54.7% due to the large cavities. The encapsulation of drug from leakage in the blood environment was realized as PNVCL collapsed at physiological temperature. The fracture of pH-liable imine bonds in a slightly acidic tumor environment triggered the burst release of cargo. The Fe3O4@V-mSiO2-PNVCL showed super paramagnetic behavior (21.01 emu∙g−1) which could achieve magnetic targeting. The MTT assay confirmed that the nanoparticles exhibited low cytotoxicity. Furthermore, the cellular uptake experiments indicated that DOX-loaded nanoparticles were successfully internalized into cancer cells. Therefore, the composite nanoparticles are ideal choices for drug carriers.

A hybrid formulation of porous silicon nanoparticle with carboxymethyl cellulose for enhanced drug loading

Porous silicon nanoparticles (pSiNPs) have received considerable spotlight in drug delivery systems due to their biocompatibility, drug loading capacity, and easy surface modification. Despite these merits, the degradation rate control of pSiNPs in biological environments remains a challenge for sustained-release applications. In this study, we introduce a novel formulation of pSiNPs-based coated with carboxymethyl cellulose (pSiNPs-CMC) for the first time. The drug loading and release behavior of pSiNPs-CMC, featuring representative anticancer drugs such as doxorubicin, gemcitabine, paclitaxel, and SN-38, were extensively characterized. Notably, the CMC coating on pSiNPs resulted in an increase in loading efficiency of over 60% both for hydrophilic and hydrophobic drugs, while ensuring a controlled and tailored drug release profile. Our findings present the potential of the pSiNPs-CMC composite as a robust and versatile platform, overcoming conventional limitations in drug specificity and representing a significant advancement in sustained and personalized drug delivery systems.

Eco-friendly synthesis of mesoporous bioactive glass ceramics and functionalization for drug delivery and hard tissue engineering applications

Hard tissue regenerative mesoporous bioactive glass (MBG) has traditionally been synthesized using costly and toxic alkoxysilane agents and harsh conditions. In this study, MBG was synthesized using the cheaper reagent SiO2 by using a co-precipitation approach. The surface properties of MBG ceramic were tailored by functionalizing with amino and carboxylic groups, aiming to develop an efficient drug delivery system for treating bone infections occurring during or after reconstruction surgeries. The amino groups were introduced through a salinization reaction, while the carboxylate groups were added via a chain elongation reaction. The MBG, MBG-NH2, and MBG-NH-COOH were analyzed by using various techniques: x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET), scanning electron microscopy and energy-dispersive x-ray spectroscopy. The XRD results confirmed the successful preparation of MBG, and the FTIR results indicated successful functionalization. BET analysis revealed that the prepared samples were mesoporous, and functionalization tuned their surface area and surface properties. Cefixime, an antibiotic, was loaded onto MBG, MBG-NH2, and MBG-NH-COOH to test their drug-carrying capacity. Comparatively, MBG-NH-COOH showed good drug loading and sustained release behavior. The release of the drug followed the Fickian diffusion mechanism. All prepared samples displayed favorable biocompatibility at higher concentration in the Alamar blue assay with MC3T3 cells and exhibited the good potential for hard tissue regeneration, as carbonated hydroxyapatite formed on their surfaces in simulated body fluid.

The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

Cyclophosphamide Loading and Controlled Release in MIL-100(Fe) as an Anti-breast Cancer Carrier: In vivo In vitro Study.

Biocompatible MIL-100 (Fe), a metal organic framework material, has recently attracted increasing attention in biomedical engineering. The high surface area, pore volume, and accessible Lewis acid sites make MIL-100 (Fe) a proper candidate for hydrophobic anticancer drug loading and storage. In this study, a novel investigation of cyclophosphamide (CP) -loaded MIL-100(Fe) (MIL- 100(Fe)/CP) and a simulation of drug loading at a molecular level is presented. This research used a facile synthesis method to prepare MIL-100(Fe), which addresses the high temperature and pressure challenges of synthesis methods. MIL-100(Fe) and MIL-100(Fe)/CP were characterized using x-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), Fourier transform infrared (FTIR), and field emission scanning electron microscopy (FESEM). The carriers' drug loading and release behavior are determined by using UV-visible spectrophotometry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is applied to examine the biocompatibility and the anticancer effect of MIL-100(Fe)/CP on the human breast cancer cell line (MCF-7). In vivo</i> antitumor experiments and histological observation reveal inhibition properties of MIL-100(Fe)/CP on the tumor cells. MIL-100(Fe)/CP, with 37.41% drug payload, represents impressive antitumor activity.

Titanium-based metal-organic frameworks as pH-responsive drug delivery carriers of 5-Fluorouracil

In this study, we synthesized two titanium-based metal-organic frameworks (Ti-MOFs), namely MIL-125 and MIL-125-NH2, known for their excellent biocompatibility, as potential carriers for the anti-cancer drug 5-Fluorouracil (5-FU). We conducted comprehensive examinations of their morphologies, particle size distributions using SEM, stability, permanent porosity, and in vitro drug loading and release behaviors. Both materials demonstrated significant advantages due to their excellent stability, large surface area, and nanoscale sizes, which resulted in a high capacity for loading 5-FU. Significantly, both MIL-125 and MIL-125-NH2 consistently displayed pH-responsive release of 5-FU. This result may not only help to enhance the therapeutic efficacy of 5-FU but is also expected to improve its targeting potential. Our current research suggests that Ti-MOFs hold great promise as carriers for 5-FU in cancer treatment, offering guidance for the design and development of new customized and responsive drug delivery system.

Targeted Delivery of Arctigenin Using Sialic Acid Conjugate-Modified Liposomes for the Treatment of Breast Cancer.

Arctigenin (ATG) is a broad-spectrum antitumor drug with an excellent inhibitory effect on malignant tumors such as breast cancer, glioblastoma, liver cancer, and colon cancer. However, the clinical application of ATG is limited by its poor water solubility and quick hydrolysis in the liver, intestine, and plasma, which might hinder its application. Sialic acid (SA) recognizes selectin receptors overexpressed on the surface of tumor-associated macrophages. In this study, SA was conjugated with octadecylamine (ODA) to prepare SA-ODA, which was employed to prepare SA functionalized nanoliposomes (SA-Lip) to achieve breast cancer targeting. The formulations were finely optimized using the Box-Behnken design to achieve higher ATG loading. The size, ζ potential, entrapment efficiency, drug loading, and release behavior of ATG@SA-Lip were fully investigated in comparison with conventional ATG@Lip. The ATG@SA-Lip displayed more potent cytotoxicity and higher cellular internalization compared to ATG@Sol and ATG@Lip in both MCF7 and 4T1 cells. Notably, ATG@SA-Lip showed the lowest impact on the immune system. Our study demonstrates that SA-Lip has strong potential as a delivery system for the targeted delivery of ATG.

Design of carboxymethylcellulose-conjugated polymeric prodrug micelles for enhanced in vivo performance of docetaxel

Docetaxel (DTX) has become one of the most important cytotoxic drugs to treat cancer; nevertheless, its poor hydrophilicity and non-specific distribution of DTX lead to detrimental side effects. In this article, we devised carboxymethylcellulose (CMC)-conjugated polymeric prodrug micelles (mPEG-CMC-DTX PMs) for DTX delivery. The ester-bonded polymeric prodrug, mPEG-CMC-DTX, was synthesized and exhibited the capacity for self-assembling into polymeric micelles. The CMC is profusely substituted and acetylated to promote the coupling rate of DTX. Covalent binding of DTX and CMC through an ester bond can be hydrolyzed to dissociate the bond under the action of esterase in the tumor. The mPEG-CMC-DTX PMs displayed promoted drug loading (>50 %, wt), commendable stability, and sustained release behavior in vitro. The gradual release of the prodrug amplified the selectivity of cytotoxicity between normal cells and tumor cells, mitigating the systemic toxicity of mPEG-CMC-DTX PMs and enabling dose intensification. Notably, mPEG-CMC-DTX PMs demonstrated a superior antitumor efficacy and low systemic toxicity due to the elevated tolerance dosage (even at 40 mg/kg DTX). In summation, mPEG-CMC-DTX PMs harmonized the antitumor efficacy and toxicity of DTX. In essence, innovative perspectives for the rational design of CMC-conjugated polymeric prodrug micelles for the delivery of potently toxic drugs were proffered.

The drug loading behavior of PAMAM dendrimer: Insights from experimental and simulation study

The drug loading behavior of PAMAM dendrimer: Insights from experimental and simulation study

Colistin-loaded aerosolizable particles for the treatment of bacterial respiratory infections

Compared to parenteral administration of colistin, its direct pulmonary administration can maximize lung drug deposition while reducing systemic adverse side effects and derived nephrotoxicity. Current pulmonary administration of colistin is carried out by the aerosolization of a prodrug, colistin methanesulfonate (CMS), which must be hydrolized to colistin in the lung to produce its bactericidal effect. However, this conversion is slow relative to the rate of absorption of CMS, and thus only 1.4 % (w/w) of the CMS dose is converted to colistin in the lungs of patients receiving inhaled CMS. We synthesized several aerosolizable nanoparticle carriers loaded with colistin using different techniques and selected particles with sufficient drug loading and adequate aerodynamic behavior to efficiently deliver colistin to the entire lung. Specifically, we carried out (i) the encapsulation of colistin by single emulsion-solvent evaporation with immiscible solvents using polylactic-co-glycolic (PLGA) nanoparticles; (ii) its encapsulation using nanoprecipitation with miscible solvents using poly(lactide-co-glycolide)-block-poly(ethylene glycol) as encapsulating matrix; (iii) colistin nanoprecipitation using the antisolvent precipitation method and its subsequent encapsulation within PLGA nanoparticles; and (iv) colistin encapsulation within PLGA-based microparticles using electrospraying. Nanoprecipitation of pure colistin using antisolvent precipitation showed the highest drug loading (55.0 ± 4.8 wt%) and spontaneously formed aggregates with adequate aerodynamic diameter (between 3 and 5 μm) to potentially reach the entire lung. These nanoparticles were able to completely eradicate Pseudomonas aeruginosa in an in vitro lung biofilm model at 10 µg/mL (MBC). This formulation could be a promising alternative for the treatment of pulmonary infections improving lung deposition and, therefore, the efficacy of aerosolized antibiotics.

Bioinspired microrobots: Opportunities and challenges in targeted cancer therapy.

Chemotherapy is still the most effective technique to treat many forms of cancer. However, it also carries a high risk of side effects. Numerous nanomedicines have been developed to avoid unintended consequences and significant negative effects of conventional therapies. Achieving targeted drug delivery also has several challenges. In this context, the development of microrobots is receiving considerable attention of formulation scientists and clinicians to overcome such challenges. Due to their mobility, microrobots can infiltrate tissues and reach tumor sites more quickly. Different types of microrobots, like custom-made moving bacteria, microengines powered by small bubbles, and hybrid spermbots, can be designed with complex features that are best for precise targeting of a wide range of cancers. In this review, we mainly focus on the idea of how microrobots can quickly target cancer cells and discuss specific advantages of microrobots. A brief summary of the microrobots' drug loading and release behavior is provided in this manuscript. This manuscript will assist clinicians and other medical professionals in diagnosing and treating cancer without surgery.

Development of Resistant Starch-Pectin Microsphere for Improving Oral Colon-specific Drug Delivery of 5-Fluorouracil

Conventional chemotherapy is ineffective for colorectal cancer as the drug moiety does not reach its intended site. 5-Fluorouracil (5-FU) microspheres aimed at colon-specific drug delivery have been developed by using the solvent evaporation technique in this study. The influence of utilizing different percentages of resistant starch-pectin polymer on the drug loading, encapsulation efficiency, and release behavior of the drug was investigated. The characterization of prepared microspheres was done by shape, surface morphology, drug loading, encapsulation efficiency and in vitro drug release studies. Drug-polymer interactions and drug stability were investigated by Differential Scanning Calorimetry (DSC) and FTIR spectroscopy. The 5-Fluorouracil polymeric microspheres that were formulated utilizing a resistant starch (RS) and pectin polymer displayed ideal physicochemical properties and spherical particles. The targeted microspheres demonstrated a high drug loading, encapsulation efficiency, and a satisfactory drug release pattern over the time period of 8 hours. Studies on drug release conducted under conditions that simulate stomach to colon transit have demonstrated that the drug was prevented from being released in the physiological conditions of the stomach and small intestine. Creating a new multiparticulate system using RS-pectin microspheres in order to forecast the protection that the combination might provide to the dosage form that will ensure localized drug release in the colon. Finally, it was found that the 5-Fluorouracil polymeric microsphere is a suitable microcarrier for effective colon-specific drug delivery tools with increased chemotherapeutic efficacy. Bangladesh Pharmaceutical Journal 26(1): 36-44, 2023 (January)

Casein-Based Nanoparticles: A Potential Tool for the Delivery of Daunorubicin in Acute Lymphocytic Leukemia

The aim of this study was to develop casein-based nanoscale carriers as a potential delivery system for daunorubicin, as a pH-responsive targeting tool for acute lymphocytic leukemia. A coacervation technique followed by nano spray-drying was used for the preparation of drug-loaded casein nanoparticles. Four batches of drug-loaded formulations were developed at varied drug-polymer ratios using a simple coacervation technique followed by spray-drying. They were further characterized using scanning electron microscopy, dynamic light scattering, FTIR spectroscopy, XRD diffractometry, and differential scanning calorimetry. Drug release was investigated in different media (pH 5 and 7.4). The cytotoxicity of the daunorubicin-loaded nanoparticles was compared to that of the pure drug. The influence of the polymer-to-drug ratio on the nanoparticles' properties such as their particle size, surface morphology, production yield, drug loading, entrapment efficiency, and drug release behavior was studied. Furthermore, the cytotoxicity of the drug-loaded nanoparticles was investigated confirming their potential as carriers for daunorubicin delivery.

Novel Monomethoxy Poly(Ethylene Glycol) Modified Hydroxylated Tung Oil for Drug Delivery.

Novel monomethoxy poly(ethylene glycol) (mPEG) modified hydroxylated tung oil (HTO), denoted as mPEG-HTO-mPEG, was designed and synthesized for drug delivery. mPEG-HTO-mPEG consists of a hydroxylated tung oil center joined by two mPEG blocks via a urethane linkage. The properties of mPEG-HTO-mPEG were affected by the length of the mPEG chain. Three mPEG with different molecular weights were used to prepare mPEG-HTO-mPEG. The obtained three mPEG-HTO-mPEG polymers were characterized by nuclear magnetic resonance (NMR), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC), respectively. Furthermore, the particle sizes of mPEG-HTO-mPEG micelles were evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). A critical aggregation concentration (CAC) ranged from 7.28 to 11.73 mg/L depending on the chain length of mPEG. The drug loading and release behaviors of mPEG-HTO-mPEG were investigated using prednisone acetate as a model drug, and results indicated that hydrophobic prednisone acetate could be effectively loaded into mPEG-HTO-mPEG micelles and exhibited a long-term sustained release. Moreover, compared with HTO, mPEG-HTO-mPEG had no obvious cytotoxicity to HeLa and L929 cells. Therefore, monomethoxy poly(ethylene glycol) modified hydroxylated tung oil mPEG-HTO-mPEG may be a promising drug carrier.

Mesoporous silica (SBA-15) with enriched amidoxime functionalities for pH-controlled anticancer drug delivery

Amidoxime (AMI), an amphoteric functional ligand, mesoporous silica material (SBA-15@AMI NPs) was prepared and the pH-responsive drug release behavior was examined using Dox as model anticancer drug. Further, the cytocompatibility and the cell uptake results revealed that SBA-15@AMI NPs could be applied as pH-responsive drug delivery applications in cancer therapy. • Developing pH- responsive drug delivery system is attracted a great concern. • An amphoteric ligand functionalized SBA-15@AMI NPs for pH-responsive drug delivery system has been proposed. • The SBA-15@AMI NPs is applicable for delivery of anticancer drugs in cancer therapy. Amidoxime (AMI) functionalized mesoporous silica material (SBA-15@AMI NPs) was synthesized by surface modification approaches. This method allows for the creation of a higher concentration of amidoxime ligand groups to the SBA-15's surface without affecting the morphology. The synthesized SBA-15@AMI NPs were verified using a range of instrumental characterizations. Further, the drug loading and pH-responsive release behavior of the SBA-15@AMI NPs were examined using Dox as model anticancer drug. The biocompatibility and cellular uptake behavior was studied using MCF-7 cell line. Overall, the prepared SBA-15@AMI NPs could be applied as pH-responsive drug delivery applications in cancer therapy.

PH-responsive magnetic Fe3O4/carboxymethyl chitosan/aminated lignosulfonate nanoparticles with uniform size for targeted drug loading

In order to improve the effect of anti-tumor drugs, a magnetic delivery system for targeted drug was reported. Firstly, aminated lignosulfonate (ALS) and carboxymethyl chitosan (CMCS) were used to fabricate nano Fe3O4 to obtain pH-responsive magnetic Fe3O 4 /CMCS/ALS nanoparticles. Then the nanoparticles were loaded with doxorubicin hydrochloride (DOX), realizing the targeted delivery and controlled release of anti-tumor drugs. It was found that the amount of crosslinking agent and emulsifier were the key factors affecting the morphology and size of the magnetic nanoparticles. Under optimized conditions, the particle size was about 79.9–169.9 nm, exhibiting excellent pH responsiveness. When the drug-to-material ratio was 11:10, the DOX loading rate and the encapsulation rate of the nanoparticles was 48.68 % and 86.23 %. While the Fe3O4 /CMCS/ALS-DOX particles could release 63.14 %, 56.71 %, and 14.28 % of DOX at pH 4.0, 5.3, and 7.4, respectively. The results showed that the Fe3O4 /CMCS/ALS particles exhibited excellent drug loading and release behavior based on the pH responsiveness, which could be described by Langmuir adsorption model and Fick's law of diffusion respectively. MTT assay and Live/dead staining experiments also showed that the drug-loaded particles had obvious growth inhibition on cancer cells.

Polyhedral oligomeric silsesquioxane (POSS)-modified citric-acid coated magnetic Fe3O4 nanoparticles for anticancer drug delivery

In this work, magnetic nanoparticles coated with citric acid (Fe3O4@Cit) were synthesized via co-precipitation strategy. Then, Fe3O4@Cit was modified with octa-aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt nanoparticles (OAPOSS NPs) by amidation reaction between carboxylic acid end groups on Fe3O4@Cit and the amine groups of OAPOSS surface (Fe3O4@Cit@OAPOSS). The key point of this approach is utilizing a symmetric nanosized cagelike POSS NPs as coating material to obtain novel hybrid drug nanocarrier. The successful preparation of nanocarrier (Fe3O4@Cit@OAPOSS) was confirmed by various techniques. Drug loading and release behaviors of Fe3O4@Cit@OAPOSS were evaluated using doxorubicin (DOX), a standard anticancer model drug, in neutral and acidic conditions. Moreover, Higuchi and Korsmeyer-Peppas models were used to study the release kinetics of DOX. Obtained results confirmed the suitability of Fe3O4@Cit@OAPOSS as a potential novel nanocarrier for drug delivery.

Chitosan based hybrid hydrogels for drug delivery: Preparation, biodegradation, thermal, and mechanical properties

AbstractIn the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5‐fluorouracil. The fabricated hydrogels were characterized via FT‐IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5‐FU due to these properties.

Thermo-Sensitive Poly (N-isopropylacrylamide-co-polyacrylamide) Hydrogel for pH-Responsive Therapeutic Delivery.

Stimuli-response polymeric nanoparticles have emerged as a carrier system for various types of therapeutic delivery. In this study, we prepared a dual pH- and thermo-sensitive copolymer hydrogel (HG) system (PNIPAm-co-PAAm HG), using N-isopropyl acrylamide (NIPAm) and acrylamide (AAm) as comonomers. The synthesized PNIPAm-co-PAAm HG was characterized using various instrumental characterizations. Moreover, the PNIPAm-co-PAAm HG’s thermoresponsive phase transition behavior was investigated, and the results showed that the prepared HG responds to temperature changes. In vitro drug loading and release behavior of PNIPAm-co-PAAm HG was investigated using Curcumin (Cur) as the model cargo under different pH and temperature conditions. The PNIPAm-co-PAAm HG showed pH and temperature-responsive drug release behavior and demonstrated about 65% Cur loading efficiency. A nearly complete release of the loaded Cur occurred from the PNIPAm-co-PAAm HG over 4 h at pH 5.5 and 40 °C. The cytotoxicity study was performed on a liver cancer cell line (HepG2 cells), which revealed that the prepared PNIPAm-co-PAAm HG showed good biocompatibility, suggesting that it could be applied as a drug delivery carrier. Moreover, the in vitro cytocompatibility test (MTT assay) results revealed that the PNIPAm-co-PAAm HG is biocompatible. Therefore, the PNIPAm-co-PAAm HG has the potential to be useful in the delivery of drugs in solid tumor-targeted therapy.