Release Kinetic Models Research Articles

Abstract 839: Characterization and evaluation of modified 5-fluorouracil loaded liposomal nanoparticle on pancreatic and colorectal cancer cell lines

Abstract The purpose of the study is to characterize modified 5-FU (MFU) and investigate its anticancer activity in liposomal nanoparticles (MFU-Lnps) against colorectal and pancreatic cancer cell lines. Methods: The synthesized MFU was characterized by NMR and elemental analysis and formulated as MFU-Lnps. The particle size, polydispersity index (PDI), and zeta potential were determined using a particle size analyzer. The in-vitro studies were performed on 2D and 3D models of HCT-116 and MiaPaCa-2 cell lines. Cellular uptake of rhodamine (Rho) (cationic dye) alone or Rho-linked-Lnps (Rho-Lnp) was determined by confocal fluorescence microscopy. In-vitro release of MFU from MFU-Lnps was performed using PBS and methanol (3:1) at 37° C under sink conditions. To evaluate the pharmacokinetics (PK) parameters and tissue biodistribution behavior of Lnp, Lnp was loaded with gadolinium-hexanoate (Gad-Hex-Lnps), and the quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results: The 1H NMR peaks at 1.02 ppm (-C-N on 2') and 1.04 ppm (-C-N on 2''), represent the amine bond between 4-NH2 group of 5-FU and tetrahydrofuran acetate. This confirmed that the MFU was successfully synthesized. The elemental analysis of MFU showed 99.5% purity by comparing observed and theoretical values (Observed: carbon (C) = 53.57 %, hydrogen (H)= 5.64 %, and nitrogen (N) =10.44 % and, theoretical: C=53.33%, H=5.59%, and N=10.37 %). The MFU-Lnps hydrodynamic diameter was 124.9 ± 3.2 nm, polydispersity was found to be 0.16 ± 0.005, while entrapment efficiency and zeta potential values were 97.2% and -30.3 ± 12 mV, respectively. The MFU treated-2D and 3D MiaPaCa-2 cultures (IC50 values: 3.9 ± 0.9 µM2D and 6.7±1.1µM3D) was more effective than 5-FU-treated 2D and 3D MiaPaCa-2 cultures (IC50 values: 5.4 ± 0.8 µM2D and 8.5 ± 1.0 µM3D). However, MFU-Lnps treated-MiaPaCa-2 3D-organoid was 4-fold more effective compared with MFU (IC50 values: 9.8 ± 1.4 µMMFU-Lnps versus 42.3 ± 2.9 µMMFU). A similar high cytotoxicity effect of MFU-Lnp was observed when MFU-Lnp (IC50 values: 2.0 ± 0.7 µM2D and 3.4 ±0.8 µM3D) was exposed to HCT-116 2D and 3D cultures compared to MFU (3.1± 0.8µM2D and 6.8 ± 0.9 µM3D). For cellular uptake, we observed an increase in the uptake of Rho-linked-Lnps compared with Rho alone. The MFU release MFU-Lnps exhibited Higuchi release kinetics model based on the coefficient of determination (R2). For PK results, the half-life of Gad-Hex-Lnps (32.5 ± 2.6 min) was significantly high compared to that of Gad-Hex (21.5 ± 0.7 min) and, AUC of Gad-Hex-Lnps (1641 ± 499 µg/L*min) was higher than Gad-Hex (932 ± 256 µg/L*min). The accumulation of Gad-Hex-Lnps in the pancreas was remarkably higher than Gad-Hex. In conclusion, we have demonstrated that MFU-Lnps improves the anticancer efficacy of 5-FU and Lnps delivery system may improve PK parameters and increases the biodistribution of 5-FU. Citation Format: Raviteja Bulusu, Nkafu B. Ndemazie, Esther K. Frimpong, Andriana Inkoom, Joy C. Okoro, Xue Y. Zhu. Characterization and evaluation of modified 5-fluorouracil loaded liposomal nanoparticle on pancreatic and colorectal cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 839.

Application of Box-Behnken Experimental Design in Process Parameter Optimization for Production of Berberine HCl loaded Chitosan Coated Sodium Alginate Nanoparticles

Psoriasis is the most common chronic autoimmune disease. The pathophysiology, genetics, comorbidities, and biologic therapies of plaque psoriasis have seen the most rapid advances. Only a tiny percentage of the supplied dose reaches the target site in most situations (traditional dosage forms), while the balance is distributed throughout the body according to its physicochemical and biochemical properties. The current worker used nanotechnology to carry out study on the formulation and evaluation of nanoparticulate Berberine HCl loaded Chitosan coated sodium alginate nanoparticles. The Berberine HCl Nanoparticles were optimised using the Box-Behnken design. Particle size (68.82-275.78nm), zeta potential ((10.90)– (47.1 mv), percentage yield (80.75 percent - 96.21percent), percentage drug entrapment (50.95 -77.28percent), and percentage release in pH 7.4 phosphate buffer (60.848 - 95.869percent) were all found to be positive with Berberine HCl nanoparticles. Nanoparticles were found to be spherical in shape with rough surfaces, according to surface morphology (SEM). In a pH 7.4 phosphate buffer, an in-vitro drug release investigation on an optimised batch of Berberine HCl nanoparticles (BE-OPT) revealed 96.242percent (12 h) release. The release kinetic investigation with the optimised batch of Berberine HCl nanoparticles (BE-OPT) demonstrated that Higuchi's release kinetic model was followed. The chosen (optimised) nanoparticles were sealed in amber-coloured bottles with cotton plugs and caps. All were kept for six months at 40±2°C/75±5% RH and examined for their physical appearance and drug content at certain intervals.

Encapsulation of resveratrol in rhamnolipid-zein nanoparticles using a pH-driven method: kinetic modeling on controlled release from nanoparticles

In this study, the encapsulation of resveratrol (Res) in zein-rhamnolipid (RL) composite nanoparticles (NPs) by a pH-driven method and its relationship with the controlled release behavior of the NPs were investigated. The properties of the produced NPs were elucidated with different zein-RL mass ratios and encapsulation of different amounts of Res. The NPs had relatively high encapsulation efficiency, loading capacity, stability, and cumulative release percentages. The SEM analysis showed the spherical NPs obtained with and without Res incorporation and the FTIR study indicated the interactions of Res with zein-RL components. The NPs had relatively good stability over a wide range of pH (4–9), salt concentration (0–200 mM) (pH = 7), and Res amount (0–160 mg) (pH = 7.4). Ultrasonic and shaking water baths were used for release studies of Res from NPs with an optimum zein-RL mass ratio of 1.0:0.6 (w/w). In vitro release studies of Res under acidic (pH = 1.2) and neutral (pH = 7.4) conditions demonstrated initial rapid release followed by slow release. The highest cumulative release percentage was obtained at pH 1.2 and 7.4 with 120 mg Res encapsulated zein-RL NPs. The release of Res from the capsules was a pH-dependent process and the cumulative release profiles were considered to be slightly higher in acidic environments. Among the controlled release kinetic models, the Weibull model gave the best fit for optimum Res-loaded NPs. Release studies indicated that zein-RL NPs have the potential to be used as delivery systems for health-promoting bioactive molecules in functional foods, nutraceutical/dietary supplements, and pharmaceutical formulations.

Design a Viable 3DP Processing for Producing Effective Controlled-Release Pesticide

Various factors such as solubility, volatility, spray drift, runoff, and photolysis prevent the pesticides to reach their desired location and realize their full potential. In this study, additive manufacturing is used to create a drug-loaded filament that can be used in Fused deposition modeling printing. The optimal printing parameters are printing temperature (170°C), hotbed temperature (25°C), printing speed 15 mm/s, filament diameter 1.55 mm, layer height 0.3 mm, nozzle diameter 0.4 mm and zero retraction speed and retraction distance. The PCL-based framework provides a scaffold for drug encapsulation and low melting temperature. The latter is the key to maintaining the integrity and chemical properties of the loaded drug. FTIR confirms the physical-mix nature of composite. XRD suggests that PCL and model drug became amorphous after printing. The PCL controlled-release can be realized through <i>in vitro</i> dissolution tests. Among the four kinetic models: the zero-order, first-order, Higuchi model, and Korsmeyer–Peppas model, the kinetic model for dissolution and drug release conforms to the Korsmeyer–Peppas model. This study provides a viable design of controlled-release pesticides by adjusting the release regulator content and type to meet the precision pest-control needs. This 3DP tablet has higher drug loading, controllable drug loading, stable drug release ability, UV shielding performance, and an easy manufacturing process. There is no need for expensive and special equipment to produce the desired functionality, which greatly reduces production costs and simplifies the production process.

In Silico Guided Nanoformulation Strategy for Circumvention of Candida albicans Biofilm for Effective Therapy of Candidal Vulvovaginitis.

Candidal vulvovaginitis involving multispecies of Candida and epithelium-bound biofilm poses a drug-resistant pharmacotherapeutic challenge. The present study aims for a disease-specific predominant causative organism resolution for the development of a tailored vaginal drug delivery system. The proposed work fabricates a luliconazole-loaded nanostructured lipid carrier-based transvaginal gel for combating Candida albicans biofilm and disease amelioration. The interaction and binding affinity of luliconazole against the proteins of C. albicans and biofilm were assessed using in silico tools. A systematic QbD analysis was followed to prepare the proposed nanogel using a modified melt emulsification-ultrasonication-gelling method. The DoE optimization was logically implemented to ascertain the effect of independent process variables (excipients concentration; sonication time) on dependent formulation responses (particle size; polydispersity index; entrapment efficiency). The optimized formulation was characterized for final product suitability. The surface morphology and dimensions were spherical and ≤300 nm, respectively. The flow behavior of an optimized nanogel (semisolid) was non-Newtonian similar to marketed preparation. The texture pattern of a nanogel was firm, consistent, and cohesive. The release kinetic model followed was Higuchi (nanogel) with a % cumulative drug release of 83.97 ± 0.69% in 48 h. The % cumulative drug permeated across a goat vaginal membrane was found to be 53.148 ± 0.62% in 8 h. The skin-safety profile was examined using a vaginal irritation model (in vivo) and histological assessments. The drug and proposed formulation(s) were checked against the pathogenic strains of C. albicans (vaginal clinical isolates) and in vitro established biofilms. The visualization of biofilms was done under a fluorescence microscope revealing mature, inhibited, and eradicated biofilm structures.

Preparation and Characterization of Silymarin Gel: A Novel Topical Mucoadhesive Formulation for Potential Applicability in Oral Pathologies.

Silybum marianum has been used for centuries by herbalists and physicians to treat different forms of liver diseases. It contains flavonoid, which has antioxidant, anti-inflammatory, antifibrotic and anticancer properties. The objective of this research was to develop a silymarin-based mucoadhesive gel for prolonged release in oral mucosa and to evaluate the same by using in vitro drug release kinetic models and ex vivo methods for drug permeation using chicken buccal mucosa. The mucoadhesive gel was formulated in different trials by varying the concentration of silymarin and polymer. Out of 10 formulation trials, the F10 optimized trial was characterized for in vitro physicochemical parameters such as pH, homogeneity, viscosity, stability, drug content, in vitro drug release, in vitro antioxidant assay and ex vivo permeation study. Trial 10 was chosen as the best trial formulation among the other trials and was marked as an optimal trial. The physicochemical properties observed were pH to be 6.4 ± 0.01, the gel free of lumps, spreadability of 23.75 ± 0.03 and drug content of 32.77 ± 0.20 mg/g. It had no physiological changes such as color shift or fluid exudate segregation after 6 months of storage at room temperature. In vitro drug release established the presence of a non-fickian mechanism and demonstrated dose-dependent antioxidant activity. Ex vivo findings indicated 21.97 ± 0.18% release, proving that the gel can permeate through the oral mucosal membrane. Our future research will concentrate on expanding the therapeutic scope by developing the formulation trial F10 to a nanoformulation and conducting clinical trials for its potential use in various oral diseases.

Temperature controlled microcapsule loaded with Perilla essential oil and its application in preservation of peaches.

In this study, Perilla frutescens essential oil (PEO) loaded microcapsules (PEOM) were successfully prepared and their thermal stability, temperature-responsive releasing effect, antioxidant activity, antibacterial activity, and preservation of peach were systematically investigated. PEOM showed excellent encapsulation efficiency (91.5%) with a core-shell ratio of 1.4:1 and exhibited high thermal stability, indicating that PEOM could effectively maintain PEO release rate. In vitro assays indicated that the optimal kinetic model for PEO release fitted well with first order with a diffusion mechanism. A high level of antioxidant and antibacterial activity of PEOM was maintained. In addition, owing to its sustained release, PEOM could prolong the shelf life of peaches significantly. Therefore, PEOM has potential application and development prospects in the field of food preservation.

Design of polyacrylamide grafted sesbania gum-mediated pH-responsive IPN-based microbeads for delivery of diclofenac sodium: In-vitro-in-vivo characterizations

Microwave-assisted grafting of polyacrylamide on sesbania gum (PAAM-g-SG) was implemented employing a 32 full factorial experimental design and was hydrolyzed using sodium hydroxide (NaOH) to form H-PAAM-g-SG. Further, the diclofenac sodium-loaded novel pH-sensitive interpenetrating polymeric network (IPN) microbeads were designed using an optimized H-PAAM-g-SG and sodium alginate (SA). Different spectroscopic analysis including FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis, thermal analysis, etc. was performed to confirm the synthesis of PAAM-g-SG and diclofenac-loaded pH-sensitive IPN H-PAAM-g-SG-SA microbeads. Here, Ca+2 ions combine with two strands of SA and form a round-shape structure that encloses uncross-linked H-PAAM-g-SG polymer and diclofenac sodium. As well, glutaraldehyde (GL) addition improved the mechanical strength due to acetal structure between hydroxyl of H-PAAM-g-SG and aldehyde of GL. The drug entrapment was confirmed proportional relationship to the Ca+2 ions concentration whereas an increase in GL concentration resulted in a reduced drug entrapment. The pH pulsatile study assured the reversible swelling-shrinkage behavior of IPN microbeads due to the carboxyl group of PAAM-g-SG. The drug release from H-PAAM-g-SG-SA microbeads (batch: S9) was found to be 84.21 % (12h) which was non-significant (p > 0.05; f2 = 79 ∼ 90) over marketed formulation (83.31 %). Moreover, it follows the Korsmeyer Peppas (R2 = 0.996) as the best-fit release kinetic model. The pH-sensitive release of diclofenac sodium from IPN H-PAAM-g-SG-SA microbeads was assured based on in vivo anti-inflammatory activity (p < 0.05). Therefore, developed novel pH-sensitive IPN microbeads based on H-PAAM-g-SG are a promising polymeric carrier substitute for delivery of drugs actuated by a pH stimulus.

Antimicrobial food packaging application of angelica root (Angelica sylvestris) oil-loaded electrospun biofibers

The natural polymer-based electrospun fibers and fibrous mats have sparked a lot of interest in both academic and industry, and they are being used in a wide range of applications including food packaging and coating due to their biocompatibility, edibility, hydrophilicity, and nontoxicity nature. Encapsulating medicinal and aromatic plant (MAP) extracts into biofibers is a viable method for obtaining desirable biofiber properties for edible food packaging (EFP) applications. Here, angelica root (Angelica sylvestris) oil (ARO) was encapsulated into a Zein/Hyaluronic Acid/Gelatin based biofiber using an emulsion electrospinning process to fabricate EFP materials. First, volatile compounds in ARO were identified using GC/MS. It was found that fatty acid esters are the major compounds in ARO and; eucalyptol, iso-psoralen and thymol are other volatile compounds. The conductivity and viscosity of as-prepared emulsion were investigated. Then, morphology, and chemical properties of electrospun biofibers were studied using SEM and FT-IR, respectively. Then, their mechanical and antimicrobial characteristics were analyzed. Although the inhibition of ARO on bacteria differed according to the gram (G) characteristics of bacteria, inhibition of biofibers on bacteria was observed only when the amount of ARO in the biofiber was increased to 20%. Release kinetic models of eucalyptol and thymol, major essential oil components of angelica root oil, were also studied. Experimental data were fitted to different models, and it was found that thymol and eucalyptol release followed the Fickian, and non-Fickian models, respectively. Therefore, ARO loaded fibers have the potential to be an EFP material with their antimicrobial and mechanical properties.

Alendronate functionalized PLGA based nanoparticles for the effective treatment of osteoporosis-Formulation to in-vitro release kinetic studies

Osteoporosis is a bone disease caused due to the reducing bone mineral density. Porous and more fragile bones increase the risk of fractures. Hip, spine, shoulder, and wrist bones are commonly affected by osteoporosis. Low bone density is a leading cause of osteoporosis. The most efficient prescribed drugs for the treatment of osteoporosis are bisphosphonates drugs. Alendronate was the first FDA approved bisphosphonate drug for the treatment of osteoporosis. Osteoclast cells are the primary targeting site for alendronate, responsible for bone resorption. A biopharmaceutical classification system class III bisphosphonate acts as a potent, efficient, and bone resorption inhibitor drug. In the present study, alendronate functionalized PLGA based nanoparticles were developed by a solvent diffusion method and optimized for different process variables. The formulated nanoparticles were characterized for surface morphology, particle size distribution, surface charge and drug-polymer compatibility. The scanning electron microscopy and transmission electron microscopy results showed nanoparticle size in the range below 200 nm. The average particle size and zeta potential of the formulated nanoparticles were found to be 175.3 nm and -13.98 mV, respectively. The highest encapsulation efficiency was 65.23%. The release profile was dissolution medium dependent and followed by the Higuchi model of release kinetics.

Surface modification of tungsten disulfide nanosheets with pH/Thermosensitive polymer and polyethylenimine dendrimer for near-infrared triggered drug delivery of letrozole

In the present work, pH and thermosensitive polymer, N-isopropylacrylamide-co-allyl acetoacetate modified polyethylenimine dendrimer-grafted tungsten disulfide, is successfully synthesized for triggered letrozole delivery for cancer chemotherapy. The nanocarrier was characterized by Fourier-transform infrared spectra, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, elemental analysis, and X-ray diffraction techniques. Different parameters influencing the sorption of drug such as pH, contact time, and temperature were studied to optimize the operating conditions. It was shown that drug release is enhanced under the near infrared laser irradiation, indicating that the nanocarrier can be used as dual responsive systems, with drug release controllable through laser irradiation. Moreover, after 6 h of simulated release in vitro, the letrozole release amount of the nanocarrier was 88.76 % at pH 5.6 (37 °C), 99.47 % at pH 5.6 (45 °C), 33.60 % at pH 7.4 (37 °C), and 73.35 % at pH 7.4 (45 °C), showing the pH and thermo-responsiveness. The different release kinetic models were investigated and it has been shown that release curve of drug best followed the Higuchi model for the release of letrozole from the nanocarrier. The release of letrozole from the nanocarrier occurred through non-Fickian diffusion mechanism. Upon 808 nm near laser irradiation, it shown that 100 % of letrozol was released. The pH and thermosensitive polymer absorb the NIR light and as a result begin to dissipate heat. This heat produced induces a shrinkage of the polymer facilitating the release of the drug. Also, adsorption of drug on the pH and thermosensitive polymer is best explained by Langmuir isotherm and pseudo-second-order kinetic models.

Formulation and Evaluation of Natural Gel Containing Ethanolic Extract of Pandanus amaryllifolius R. Using Various Gelling Agents

Ethanol extract of Pandanus amaryllifolius leaves contains quercetin has anti-inflammatory properties. The gel dosage form is very appropriate for wound healing therapy because it gives a cold sensation to the skin. This study aims to formulate a P. amaryllifolius gel by variation of a gelling agent to compare the effect of a natural gelling agent, semi-synthetic gelling agent, and synthetic gelling agent on the physical characteristics of the gel. The gel formulation was made in three formulas. Evaluations include organoleptic, homogeneity, spreadability, adhesion, pH, and viscosity. The optimum gel formula was tested for release study using a dissolution apparatus 5. Determination of release kinetics model using the kinetics approach of zero-order, first-order, Higuchi, and Korsmeyer-Peppas. The organoleptic shows the gel's dark green color, P. amaryllifolius aromas, and good homogeneity. The gel formulas had pH values that matched the physical quality criteria of the gel. Data obtained for the spreadability test for F1, F2, and F3 were 12.16, 14.66, and 10.75 g.cm/sec, respectively. The F1, F2, and F3 adhesion test results were 11.66, 10, and 47.33, respectively. The viscosity of F1 was 15750 cps, F2 was 4807 cps, and F3 was 19380 cps. This study concludes that the optimum formula is obtained from the gelling agent of Na-CMC as a gelling agent. The number of quercetins released from F2 was 42.76%, and the release kinetics model followed the kinetics of Higuchi.

RETRACTED ARTICLE: Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout

BackgroundAllopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo.MethodologyALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension.ResultsThe optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague–Dawley rats after transdermal administration as compared to oral ALP suspension.ConclusionALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Gliclazide in Binary and Ternary Systems Improves Physicochemical Properties, Bioactivity, and Antioxidant Activity

The poor solubility of the antidiabetic drug gliclazide (Glc) is due to its hydrophobic nature. This research is aimed at improving Glc's solubility and drug release profile, as well as at investigating additional benefits such as bioactivity and antioxidant activity, by forming binary complexes with HPβCD at different w/w ratios (1 : 1, 1 : 2.5, 1 : 4, and 1 : 9) and ternary complexes with HPβCD and Tryp at 1 : 1 : 1, 1 : 1 : 0.27, 1 : 2.5 : 0.27, 1 : 3.6 : 3.6, 1 : 4 : 1, and 1 : 9 : 1, respectively. Complexes were prepared by the physical mixing (PM) and solvent evaporation (SE) methods. The prepared inclusion complexes were meticulously characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. To verify our findings, the inclusion complexes were evaluated by equilibrium solubility, in vitro drug release profile, kinetic models, and antidiabetic and antioxidant activities in animal models. Our results demonstrated that the solubility and drug release profile were found to be enhanced through binary as well as ternary complexes. Notably, ternary complexes with a ratio of 1 : 9 : 1 showed the highest solubility and drug release profile compared to all other preparations. Data on antioxidant activity indicated that the ternary complex had the higher total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) activity than the binary complex and Glc alone, in contrast to the diabetic group. In vivo antidiabetic activity data revealed a high percentage reduction in the blood glucose level by ternary complexes (49-52%) compared to the binary complexes (45-46%; p ≤ 0.05). HPβCD and Tryp provide a new platform for overcoming the challenges associated with poorly soluble Glc by providing greater complexing and solubilizing capabilities and imparting ancillary benefits to improve the drug's antidiabetic and antioxidant activities.

The Formation of Self-Assembled Nanoparticles Loaded with Doxorubicin and d-Limonene for Cancer Therapy.

Self-assembled nanoparticles present unique properties that have potential applications in the development of a successful drug delivery system. Doxorubicin (DOX) is an important anti-neoplastic anthracycline chemotherapeutic drug widely described. However, it suffers from serious dose-dependent cardiotoxicity. d-Limonene is a major constituent of numerous citrus oils that is considered a specific monoterpene against free radicals producing antioxidant activity. Herein, we aimed to design three types of self-assembled nanodelivery systems (nanoemulsion, niosomes, and polylactide nanoparticles) for loading both DOX and d-limonene to enhance the solubilization of d-limonene and provide antioxidant activity with excellent anticancer activity. As confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The zeta potential values were above -30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release model for all developed nanoparticles was the Peppas-Sahlin model, demonstrating DOX release through Fickian diffusion phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of d-limonene. The cytotoxicity study of the DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the cardioprotective effect of d-limonene in combination with DOX.

Preparation and Evaluation of Sustained Release Tablet of Rifaximin by using Cross linked Sodium Alginate

Rifaximin treats traveler's diarrhea and irritable bowel syndrome by stopping the growth of the bacteria that cause diarrhea. Rifaximin treats hepatic encephalopathy by stopping the growth of bacteria that produce toxins and that may worsen liver disease. The short half life and high frequency of administration of drug makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of Rifaximin using sodium alginate and cross linked sodium alginate and to evaluate the drug release kinetics. In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method. The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.

PH-sensitive alginate hydrogel for synergistic anti-infection

This work designed a pH-sensitive sodium alginate hydrogel for combating bacterial infection caused by tissue damage. The antibacterial hydrogels were prepared using sodium alginate, citric acid, and vancomycin by one-step in situ method. Vancomycin (Van) was loaded into hydrogels via reversible imine bonds for controlled drug delivery. The morphology, swelling properties, and antibacterial activity of hydrogel were characterized. The hydrogel shown strong water absorbent behavior and pH-dependent performance. The result under weak acid conditions, the drug release rate of van-loaded gel was faster than neutral and alkaline conditions and followed zero-order kinetic release model, and the cumulative release amount could reach 86.7 % over 320 min. The van-loaded gel had highly effective antibacterial activity in a weak acid environment, the combination of citric acid and vancomycin had a synergistic therapeutic effect for acute infection. The drug-loaded hydrogel shows good biocompatibility. Compared with gauze, the drug-loaded hydrogel exhibited good coagulation properties, high platelet adhesion, high fluid absorption capacity, and proper balance of fluid on the wound bed. This work proposed this simple alginate-based drug delivery system has potential applications in the field of clinical treatment of infections.

Aggregation-induced emission (AIE) nanoparticles based on γ-cyclodextrin and their applications in biomedicine

Amphiphilic AIE nanoparticles (CD-TPE) were obtained by linking γ-cyclodextrin (γ-CD) and 1, 2-diphenyl-1, 2-(p-hydroxyphenyl)-ethylene (OH-TPE-OH) by an esterification reaction using hexamethylene diisocyanate (HMDI) in a one-step process. The CD-TPE was characterized by FTIR, 13C NMR, DSC, XRD, particle size analysis, TEM, and FL. The obtained CD-TPE had good water dispersibility and could self-assemble into AIE nanoparticles. The large cavity of CD-TPE provided convenient conditions for the loading of doxorubicin (DOX) and slow-release DOX with the loading and release rates of 67.4 % and 71.3 % (pH = 5.4), respectively. The DOX release kinetic model was suitable for the Bhaskar model. Cytotoxicity analysis and cell imaging of CD-TPE were performed, showing that CD-TPE has good biocompatibility and excellent cell imaging performance. Moreover, both in vitro and in vivo antitumor experiments showed that CD-TPE has promising applications in drug delivery.

3D printed lactic acid bacteria hydrogel: cell release kinetics and stability

In this study, a new type of 3D printed living biological hydrogel was developed by integrating lactic acid bacteria (LAB) into biocompatible and non-toxic polymer materials. Interestingly, the living materials loaded with LAB can be freeze-dried and reused for more than 100 times. The bio-hydrogel can be used to co-culture different LAB and keep its fermentation performance stable in long-term use. The release kinetics model and response surface method were used to simulate and optimize the bacteria release mode in the bio-hydrogel. The results show that the release of bacteria from hydrogel is regulated by the coupling of Fickian diffusion and polymer swelling. The stability of LAB hydrogel was evaluated by reuse experiments. The images of confocal microscopy and scanning electron microscope showed that the bacteria with high cell viability were distributed in the hydrogel and intact structure of the living hydrogel was maintained after 100 times of reuse as yoghurt starter. In conclusion, the 3D printed LAB bio-hydrogel developed in this study has the advantage of reuse and sustainability, which is expected to open up a new way for the preparation of food culture starter.

Lecithin sensitized thermo-sensitive niosome using NIR-carbon dots for breast cancer combined chemo-photothermal therapy

In this work, a new class of thermo-sensitive niosome (TS-Nio) was synthesized using lecithin and NIR-carbon dots, for combined chemo-photothermal therapy. TS-Nio (200 nm) and noisome (240 nm) were synthesized using thin layer method and were stable for 14 days in water, buffer, and cellular environment. CQDs with a hydrodynamic diameter of 2.0 ± 0.5 nm (during 14 days) were synthesized by the hydrothermal method, and their photothermal, and quantum efficiency were 24.3% and 67%, respectively. Synthesized CQDs had repeating maximum temperature of 55 ± 0.2 °C in four 10-min irradiation cycles (LASER 808 nm) and photothermal therapy effect of 40%, 46%, 44%, and 48% for MCF-10A, MCF-7, MDA-MB-231, SKBR-3 cells, respectively. Drug and CQDs were loaded in the niosomes, and the release difference between normal and cancer cell conditions were 55% and 21% for TS-Nio and niosome, respectively. The drug release kinetic model was Komsmeyer & Peppas. Chemotherapy on MCF-7 cancer cells using Dox-loaded niosomes showed the maximum toxicity of 46% and 37% for TS-Nio and niosome, respectively. The chemophotothermal therapy on MCF-10A, MCF-7, MDA-MB-231, SKBR-3 cells using drug and CQDs loaded niosomes with 10 min laser irradiation were 40%, 88%, 89%, 15% for TS-Nio, and 17%, 61%, 67%, 29% for niosome respectively. The results showed perfect targeting and effective chemophotothermal therapy of TS-Nio on MCF-7 and MDA-MB-231 cell lines.