Formulation of pH-sensitive aminated chitosan–gelatin crosslinked hydrogel for oral drug delivery

The objective of this study is to develop efficient pH-sensitive hydrogel based on aminated chitosan (AmCs) and gelatin (Gel) biopolymers for oral drug delivery. Herein, AmCs was chemically crosslinked with gelatin (Gel) biopolymer with different ratios, while their structures, thermal profiles and morphological properties were investigated by FTIR, TGA and SEM characterization tools, respectively. Moreover, gel-content, crosslinking density and rheological analysis were also performed. The results clarified that the developed AmCs-Gel crosslinked hydrogel displayed variable pH-sensitive swelling profiles. By increasing AmCs ratio, the swelling ratio was boosted at pH 1.2 and declined at pH 7.4. Besides, by increasing gelatin ratio in the hydrogel matrix, the loading efficiency of Oseltamivir phosphate (as a model of drug) was augmented and reached maximum value of 79.0% by AmCs-Gel (2:3) crosslinked hydrogel. The in vitro drug release profiles were investigated for 6 h in simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. Variable release profiles were realized depending on variation of AmCs and Gel ratios in the crosslinked hydrogel matrix. Finally, the formulated smart crosslinked AmCs-Gel hydrogels demonstrated acceptable biodegradability with no cellular toxicity, suggesting their applicability as pH-sensitive oral drug carriers.     

Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin

Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy.     

Design and Characterization of Maltoheptaose-b-Polystyrene Nanoparticles,as a Potential New Nanocarrier for Oral Delivery of Tamoxifen

Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL⁻¹) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs.     

Hydrophobic Chitosan Nanoparticles Loaded with Carvacrol against Pseudomonas aeruginosa Biofilms

Pseudomonas aeruginosa infections have become more challenging to treat and eradicate due to their ability to form biofilms. This study aimed to produce hydrophobic nanoparticles by grafting 11-carbon and three-carbon alkyl chains to a chitosan polymer as a platform to carry and deliver carvacrol for improving its antibacterial and antibiofilm properties. Carvacrol–chitosan nanoparticles showed ζ potential values of 10.5–14.4 mV, a size of 140.3–166.6 nm, and an encapsulation efficiency of 25.1–68.8%. Hydrophobic nanoparticles reduced 46–53% of the biomass and viable cells (7–25%) within P. aeruginosa biofilms. Diffusion of nanoparticles through the bacterial biofilm showed a higher penetration of nanoparticles created with 11-carbon chain chitosan than those formulated with unmodified chitosan. The interaction of nanoparticles with a 50:50 w/w phospholipid mixture at the air–water interface was studied, and values suggested that viscoelasticity and fluidity properties were modified. The modified nanoparticles significantly reduced viable P. aeruginosa in biofilms (0.078–2.0 log CFU·cm⁻²) and swarming motility (40–60%). Furthermore, the formulated nanoparticles reduced the quorum sensing in Chromobacterium violaceum. This study revealed that modifying the chitosan polarity to synthesize more hydrophobic nanoparticles could be an effective treatment against P. aeruginosa biofilms to decrease its virulence and pathogenicity, mainly by increasing their ability to interact with the membrane phospholipids and penetrate preformed biofilms.     

Development of Thiolated Chitosan Nanoparticles Based Mucoadhesive Vaginal Drug Delivery Systems

The aim of the present study was to evaluate the influence of the chitosan chain length on the drug loading and releasing in VFS (vaginal fluid simulant). Thiolated chitosan nanoparticles (TCS-NPs) were prepared using thioglycolic acid and 1-ethyl-3-3-(3-dimethylaminopropyl)carbodimide hydrochloride (EDC) and characterized with FTIR. The degree of thiol substitution was found out by Ellman’s method. TCS-NPs were developed using ionic cross-linking reaction with pentasodiumtripolyphosphate (TPP). Curcumin (CUR) loaded nanoparticles were obtained by encapsulation. DLS and SEM characterized these NPs with diameter between 200 ± 50 nm. Zeta potential of NPs was 11–38 mv. The maximal encapsulation efficiency was 86.26%. The in vitro drug release studies in VFA at pH 4.2 showed a sustained release profile over a period of 3 days.     

Laurus nobilis L. Essential Oil-Loaded PLGA as a Nanoformulation Candidate for Cancer Treatment

The aim of this study was to obtain essential oil (LNEO) from the Laurus nobilis L. plant, and to prepare LNEO-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) as an approach in cancer treatment. The components of the obtained LNEO were analyzed using GC-MS. The LNEO-NPs were synthesized by the single-emulsion method. The LNEO-NPs were characterized using UV-Vis spectrometry, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and a DNA binding assay, which was performed via the UV-Vis titration method. According to the results, the LNEO-NPs had a 211.4 ± 4.031 nm average particle size, 0.068 ± 0.016 PdI, and −7.87 ± 1.15 mV zeta potential. The encapsulation efficiency and loading capacity were calculated as 59.25% and 25.65%, respectively, and the in vitro drug release study showed an LNEO release of 93.97 ± 3.78% over the 72 h period. Moreover, the LNEO was intercalatively bound to CT-DNA. In addition, the mechanism of action of LNEO on a dual PI3K/mTOR inhibitor was predicted, and its antiproliferative activity and mechanism were determined using molecular docking analysis. It was concluded that LNEO-loaded PLGA NPs may be used for cancer treatment as a novel phytotherapeutic agent-based controlled-release system.     

Efficient loading and delivery of ciprofloxacin by smart alginate/carboxylated graphene oxide/aminated chitosan composite microbeads: In vitro release and kinetic studies

New composite microbeads were formulated as smart pH-sensitive vehicle for efficient delivery of ciprofloxacin (CIP) drug. Herein, carboxylated graphene oxide (CGO) was successfully impregnated into alginate (Alg) microbeads, which were then coated with aminated chitosan (AmCs) layer to form core–shell Alg/CGO@AmCs composite microbeads. Diverse analysis tools comprising FTIR, TGA, XRD and SEM were employed to characterize the developed carriers, while their swelling profiles and pH-sensitivity were examined under different pHs. The results clarified that increasing CGO and AmCs concentrations in microbeads matrix greatly protected Alg microbeads from fast disintegration at colon pH and prolonged their swelling time. Moreover, about 94.65 % of CIP drug was successfully loaded by Alg/CGO@AmCs composite microbeads compared to 61.95 % for Alg microbeads, confirming their reduced porosity. The in vitro CIP-release profiles were investigated in simulated gastrointestinal conditions. Furthermore, increasing AmCs concentration in the outer shell of composite microbeads clearly minimized the CIP burst release at the colon region and offered a sustained release performance. Besides, the CIP release mechanism was well-described by korsmeyer-peppas kinetic model. The cytotoxicity study confirmed the potential safety of the Alg/CGO@AmCs composite microbeads with human cell viability reached 98.98 %, suggesting their applicability as smart carriers for oral delivery of antibiotics.     

Endosomal pH-Responsive Fe-Based Hyaluronate Nanoparticles for Doxorubicin Delivery

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl₂/4H₂O, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 10² (DOX@HA/Fe NPs, without DMA), ~8.1 × 10² (DOX@aHA-DMA_0.36/Fe NPs), and ~9.3 × 10² (DOX@aHA-DMA_0.60/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe²⁺ and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.     

Synthesis, characterization and cytotoxicity studies of chitosan-coated tea polyphenols nanoparticles

Chitosan nanoparticles (CS-NPs) were prepared by ionic gelation method using carboxymethyl chitosan and chitosan hydrochloride as carriers of tea polyphenols. The characteristics of chitosan-coated tea polyphenols nanoparticles (CS-TP NPs) were determined by using transmission electron microscopy (TEM) and FT-IR spectroscopy. It was found that the synthesized CS-TP NPs were non-spherical in shape with an average size of 407±50nm. Meanwhile, the drug content and encapsulation rate of the nanoparticles was 8-16% and 44-83%, respectively. These CS-TP NPs also demonstrated sustained release of tea polyphenols in PBS. The antitumor of CS-TP NPs towards HepG2 cancer cells was investigated. The result showed that CS-TP NPs retained significant antitumor activities.     

Chitosan-Linseed mucilage polyelectrolyte complex nanoparticles of Methotrexate: In vitro cytotoxic efficacy and toxicological studies

The goal of this research was to develop, fabricate and analyze polymeric nanoparticles for the administration of methotrexate (MTX). Linseed mucilage and chitosan nanoparticles (NPs) were prepared using a slightly modified polyelectrolyte complex (PEC) method. The size, shape, and encapsulation effectiveness of the resultant nanoparticles were measured. MTX release profiles at gastrointestinal pH (1.2 and 7.4) and tumor pH (5.5) were examined to determine the targeted potential of NPs as pH-responsive nanocarriers. Zeta analysis showed that nanoparticles prepared by PEC have a size range of 192.1 nm to 246 nm, and PDI was 0.3 of the optimized formulation, which showed homogenous nature of prepared nanoparticles formulation. The findings demonstrated that NPs have a low polydispersity index and a positive zeta potential (PDI). The in-vitro release of the drug indicated a pH-dependent, sustained drug release up to 24 h. Blank LSMCSNPs had almost no in-vivo cytotoxicity for 14 days, while optimum MTX loaded NPs had strong antitumor effects on HepG2 and MCF-7 cells as measured by the MTT assay. Cell apoptosis induction was also checked and MCF-7 cells treated with MTX-LSMCSNPs had a significantly greater rate of apoptosis (21.2 %) than those treated with MTX alone (14.14 %). The findings show that LSMCSNPs could be a potential delivery mechanism for methotrexate to cancer cells in a secure, steady, and ideally controlled manner to improve therapeutic outcomes.     

Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study

The compound nanoparticles of chitosan (CS) and cyclodextrin (CD) loading with hydrophilic and hydrophobic drug simultaneously were prepared via the cross-linking method. Methotrexate (MTX) and calcium folinate (CaF) were selected as the model drugs. The prepared nanoparticles were characterized by FT-IR spectroscopy to confirm the cross-linking reaction between CS and cross-linking agent. X-ray diffraction (XRD) was performed to reveal the form of the drug after encapsulation. The average size of nanoparticles ranged from 308.4 ± 15.22 to 369.3 ± 30.01 nm. The nanoparticles formed were spherical in shape with high zeta potentials (higher than +30mV). In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicated the non-Fickian trend for drug release.     

Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles

The fabrication of carvacrol-loaded chitosan nanoparticles was achieved by a two-step method, i.e., oil-in-water emulsion and ionic gelation of chitosan with pentasodium tripolyphosphate. The obtained particles possessed encapsulation efficiency (EE) and loading capacity (LC) in the ranges of 14-31% and 3-21%, respectively, when the initial carvacrol content was 0.25-1.25 g/g of chitosan. The individual particles exhibited a spherical shape with an average diameter of 40-80 nm, and a positively charged surface with a zeta potential value of 25-29 mV. The increment of initial carvacrol content caused a reduction of surface charge. Carvacrol-loaded chitosan nanoparticles showed antimicrobial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli with an MIC of 0.257 mg/mL. The release of carvacrol from chitosan nanoparticles reached plateau level on day 30, with release amounts of 53% in acetate buffer solution with pH of 3, and 23% and 33% in phosphate buffer solutions with pH of 7 and 11, respectively. The release mechanism followed a Fickian behavior. The release rate was superior in an acidic medium to either alkaline or neutral media, respectively.     

ZnO Nanoparticles of Rubia cordifolia Extract Formulation Developed and Optimized with QbD Application,Considering Ex Vivo Skin Permeation,Antimicrobial and Antioxidant Properties

The objective of the current research is to develop ZnO-Manjistha extract (ZnO-MJE) nanoparticles (NPs) and to investigate their transdermal delivery as well as antimicrobial and antioxidant activity. The optimized formulation was further evaluated based on different parameters. The ZnO-MJE-NPs were prepared by mixing 10 mM ZnSO₄·7H₂O and 0.8% w/v NaOH in distilled water. To the above, a solution of 10 mL MJE (10 mg) in 50 mL of zinc sulfate was added. Box–Behnken design (Design-Expert software 12.0.1.0) was used for the optimization of ZnO-MJE-NP formulations. The ZnO-MJE-NPs were evaluated for their physicochemical characterization, in vitro release activity, ex vivo permeation across rat skin, antimicrobial activity using sterilized agar media, and antioxidant activity by the DPPH free radical method. The optimized ZnO-MJE-NP formulation (F13) showed a particle size of 257.1 ± 0.76 nm, PDI value of 0.289 ± 0.003, and entrapment efficiency of 79 ± 0.33%. Drug release kinetic models showed that the formulation followed the Korsmeyer–Peppas model with a drug release of 34.50 ± 2.56 at pH 7.4 in 24 h. In ex vivo studies ZnO-MJE-NPs-opt permeation was 63.26%. The antibacterial activity was found to be enhanced in ZnO-MJE-NPs-opt and antioxidant activity was found to be highest (93.14 ± 4.05%) at 100 µg/mL concentrations. The ZnO-MJE-NPs-opt formulation showed prolonged release of the MJE and intensified permeation. Moreover, the formulation was found to show significantly (p < 0.05) better antimicrobial and antioxidant activity as compared to conventional suspension formulations.     

Formulation of Piperine–Chitosan-Coated Liposomes: Characterization and In Vitro Cytotoxic Evaluation

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC₅₀ when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line.     

Film-Forming Spray of Water-Soluble Chitosan Containing Liposome-Coated Human Epidermal Growth Factor for Wound Healing

Human epidermal growth factor (hEGF) has been known to have excellent wound-healing activity. However, direct application to the wound area can lead to low hEGF bioavailability due to protease enzymes or endocytosis. The use of liposomes as coatings and carriers can protect hEGF from degradation by enzymes, chemical reactions, and immune reactions. Sustained release using a matrix polymer can also keep the levels of hEGF in line with the treatment. Therefore, this study aimed to develop a film-forming spray of water-soluble chitosan (FFSWSC) containing hEGF-liposomes as a potential wound dressing. The hEGF-liposomes were prepared using the hydration film method, and the preparation of the FFSWSC was achieved by the ionic gelation method. The hydration film method produced hEGF-liposomes that were round and spread with a Z-average of 219.3 nm and encapsulation efficiency of 99.87%, whereas the film-forming solution, which provided good sprayability, had a formula containing 2% WSC and 3% propylene glycol with a viscosity, spray angle, droplet size, spray weight, and occlusion factor of 21.94 ± 0.05 mPa.s, 73.03 ± 1.28°, 54.25 ± 13.33 µm, 0.14 ± 0.00 g, and 14.57 ± 3.41%, respectively. The pH, viscosity, and particle size of the FFSWSC containing hEGF-liposomes were stable during storage for a month in a climatic chamber (40 ± 2 °C, RH 75 ± 5%). A wound healing activity test on mice revealed that hEGF-liposomes in FFSWSC accelerated wound closure significantly, with a complete wound closure on day 6. Based on the findings, we concluded that FFSWSC containing hEGF-liposomes has the potential to be used as a wound dressing.     

PLGA/O-CMC载药纳米粒子的体外释药行为研究

本文以聚乳酸-乙醇酸共聚物(PLGA)和自行制备的O-羧甲基壳聚糖(O-CMC)为原料,以5-氟尿嘧啶(5-FU)为抗癌药物模型,采用自身设计的改良复乳法制备了载药纳米微粒。微粒平均粒径为98.5nm,粒径分布指数为0.192,粒子表面∈电位为61．48eV,载药率高达18．9％,包封率为86％。然后用SEM动态监测载药纳米粒子降解过程中表面形貌的变化,并连续追踪粒子降解过程中的质量损失和降解介质的pH变化。载药纳米粒子在PBS中的释药行为研究表明：(1)前12h的释药动力学符合Huguchi方程,具有一级释放特性;(2)在20天内的释药动力学符合零级释放特性。     

Synthesis and characterization of folic acid‐modified carboxymethyl chitosan‐ursolic acid targeted nano‐drug carrier for the delivery of ursolic acid and 10‐hydroxycamptothecin

Carboxymethyl chitosan (CMCS), as a water‐soluble, biocompatible, and biodegradable polymer, is an excellent carrier for a sustained drug delivery system. In this study, a amphiphilic carboxymethyl chitosan‐ursolic acid nano‐drug carrier modified by folic acid (FPCU) were prepared, and then the nano‐drug carrier wrapped another anticancer drug 10‐hydroxycamptothecin were self‐assembled into nanoparticles (FPCU/HCPT NPs). The FPCU/HCPT NPs had a suitable size, high drug loading efficiency of ursolic acid (6.4%) and 10‐hydroxycamptothecin (14.1%). The drug release study in vitro indicated that the nanoparticles have obviously sustained effect and pH sensitive behaviors, the drug release amount was higher at pH 5.5 than at pH 7.4. in vitro and in vivo study showed that the nanoparticles displayed a high antitumor efficiency to tumor cells compared with free drug. The nano delivery system as a carrier for ursolic acid (UA) and 10‐hydroxycamptothecin (HCPT) has good application prospects in cancer treatment.     

Levonorgestrel Microneedle Array Patch for Sustained Release Contraception: Formulation,Optimization and In Vivo Characterization

Background: The goal of this work was to develop a levonorgestrel liposome-loaded microneedle array patch for contraception. Methods: Levonorgestrel-loaded liposome was formulated by a solvent injection technique, characterized, and studied. Results: The formulated liposomes were characterized for particle size (147 ± 8 nm), polydispersity index (0.207 ± 0.03), zeta potential (−23 ± 4.25 mV), drug loading (18 ± 3.22%) and entrapment efficiency (85 ± 4.34%). A cryo high-resolution transmission electron microscopy and cryo field emission gun scanning electron microscopy study showed spherical shaped particles with a smooth surface. The in vitro drug release and in vivo pharmacokinetic study showed sustained behaviour of Levonorgestrel for 28 days. Conclusion: The levonorgestrel liposome-loaded microneedle array patch showed better contraception than the drug-loaded microneedle array patch.     

Optical Properties of Doxorubicin Hydrochloride Load and Release on Silica Nanoparticle Platform

Silica nanoparticles (SiO₂ NPs) synthesized by the Stober method were used as drug delivery vehicles. Doxorubicin hydrochloride (DOX·HCl) is a chemo-drug absorbed onto the SiO₂ NPs surfaces. The DOX·HCl loading onto and release from the SiO₂ NPs was monitored via UV-VIS and fluorescence spectra. Alternatively, the zeta potential was also used to monitor and evaluate the DOX·HCl loading process. The results showed that nearly 98% of DOX·HCl was effectively loaded onto the SiO₂ NPs’ surfaces by electrostatic interaction. The pH-dependence of the process wherein DOX·HCl release out of DOX·HCl-SiO₂ NPs was investigated as well. For comparison, both the free DOX·HCl molecules and DOX·HCl-SiO₂ NPs were used as the labels for cultured cancer cells. Confocal laser scanning microscopy images showed that the DOX·HCl-SiO₂ NPs were better delivered to cancer cells which are more acidic than healthy cells. We propose that engineered DOX·HCl-SiO₂ systems are good candidates for drug delivery and clinical applications.     

Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R² = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.