Release Kinetic Studies Research Articles

Effect of mango butter on the physicochemical properties of beeswax-Moringa seed oil-based oleogels for topical application

Objective The purpose of this research was to determine any connections between the characteristics of oleogels made of beeswax and the impact of mango butter. Methods Oleogel was prepared through inverted tube methods, and optimized through oil binding capacity. Other evaluations like bright field and polarized microscopy, Fourier-transform infrared (FTIR) spectroscopy, crystallization kinetics, mechanical study, and X-ray diffractometry (XRD). The drug release kinetic studies and in vitro antibacterial studies were performed. Results FTIR study reveals that the gelation process does not significantly alter the chemical composition of the individual components. Prepared gel exhibiting fluid-like behavior or composed of brittle networks is particularly vulnerable to disruptions in their network design. The incorporation of mango butter increases the drug permeation. In-vitro microbial efficacy study was found to be excellent. Conclusion The studies revealed that mango butter can be used to modify the physico-chemical properties of the oleogels.

Fabrication and Synthesis of Thiococlchicoside loaded Matrix type Transdermal Patch.

The goal of this work was to synthesize and fabricate matrix type transdermal patches based on a combination of polymers (Eudragit L100, HPMC and PVP K30), plasticizer and crosslinking agents (propylene glycol and triethyl citrate) and adhesives (Dura Tak 87-6908) to increase Thiocolchicoside (THC) absorption via topical route. This method allows avoidance of first-pass metabolism along with a consistent and extended duration of therapeutic activity. Fabrication and casting of polymeric solutions containing THC was done either in petri plates or through lab coater to get transdermal patches. Finally, the formulated patches were studied for their physicochemical and biological evaluation using scanning electron microscopy, FTIR, DSC, XRD and ex-vivo permeation studies using pig ear skin. FTIR studies confirm that the THC characteristics peaks (carbonyl (Amide I) at 1525.5 cm-1, C=O stretching (tropane ring) at 1664.4 cm-1, Amide II band (N-H stretching) at 3325.9cm-1, thioether band at 2360.7cm-1, and OH group stretching band at 3400.2 cm-1) are still present in the polymer mixture even after formulation as a transdermal patch, indicating compatibility among all excipients. While on the other hand, DSC studies confirm endothermic peaks for all the polymers along with THC with the highest enthalpy of 65.979 J/g, which is an indicator of sharp endothermic peak at 198℃, leading to the melting of THC. The percentage drug content and percentage moisture uptake of all the formulation was found in the range of 96±2.04 to 98.56±1.34% and 4.13±1.16 to 8.23±0.90%, respectively. Drug release and release kinetics studies confirm that it is dependent on the composition of individual formulation. All these findings support the possibility of using suitable polymeric composition, as well as proper formulation and manufacturing circumstances, to create a one-of-a-kind technology platform for transdermal drug administration.

Development and Assessment of Hydroxypropyl Methylcellulose-Based Floating Tablets for Ciprofloxacin HCL Using Direct Compression Technique

The key findings and conclusions include: such as formulation approaches as aim and objective Development of floating tablets using sodium bicarbonate and HPMC aimed at enhancing gastric residence time for improved drug bioavailability. Physicochemical Compliances The formulated tablets met compliance standards for various physicochemical parameters, including dimensions, floating time, tablet density, and drug content. Method of Formulations F2, F5, and F6 displayed favorable drug release profiles, with the F7 formulation exhibiting excellent release characteristics. in the evaluation the drug release kinetics studies show Kinetic analysis revealed that F2, F5, F6, and F7 formulations followed the Korsmeyer–Peppas model, indicating non-Fickian diffusion with 'n' values ranging from 0.521 to 0.633 and the stability indicates the Optimal storage conditions for stability were determined as 2-8°C for 60 days. Formulations F2, F5, F6, and F7 demonstrated stability at room temperature, 40°C, and 2-8°C for 30 days, with refrigerated storage maintaining stability throughout the 60 days. In conclusion, the developed hydrodynamically balanced tablets of Ciprofloxacin HCl exhibit promising physicochemical characteristics, dissolution profiles, and stability. These tablets hold the potential for enhancing drug bioavailability, making them a viable option for localized drug delivery in the upper gastrointestinal tract.

Spray-Dried Chitosan Hydrogel Particles as a Potential Delivery System for Benzydamine Hydrochloride.

Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present study are to obtain spray-dried microparticles based on low-molecular-weight chitosan and study their potential application as cargo systems for the orally active drug benzydamine hydrochloride. Three types of particles are obtained: raw chitosan particles (at three different concentrations), cross-linked with sodium tripolyphosphate (NaTPP) particles (at three different chitosan:NaTPP ratios), and particles coated with mannitol (at three different chitosan:mannitol ratios), all of them in the size range between 1 and 10 µm. Based on the loading efficiency and the yields of the formulated hydrogel particles, one model of each type is chosen for further investigation of the effect of the cross-linker or the excipient on the properties of the gel structures. The morphology of both empty and benzydamine hydrochloride-loaded chitosan particles was examined by scanning electron microscopy, and it was quite regular and spherical. Interactions and composition in the samples are investigated by Fourier-transformed infrared spectroscopy. The thermal stability and phase state of the drug and drug-containing polymer matrixes were tested by differential scanning calorimetry and X-ray powdered diffraction, revealing that the drug underwent a phase transition. A drug release kinetics study of the chosen gel-based structures in simulated saliva buffer (pH = 6.8) and mathematical modeling of the process were performed, indicating the Weibull model as the most appropriate one.

Formulation and Characterization of Self-Microemulsifying Drug Delivery System (SMEDDS) of Sertraline Hydrochloride.

Sertraline hydrochloride is the most widely used selective serotonin reuptake inhibitor (SSRI) for the treatment of several depressive disorders. Its applicability is limited due to extensive metabolism and poor oral bioavailability of 44 %. The current research focused on improving the solubility and oral bioavailability of Sertraline by using microemulsions developed by a self-micro emulsifying drug delivery system (SMEDDS) for significant antidepressant action. SMEDDS were developed by selecting appropriate proportions of oil, surfactant, and co-solvents and out of them isopropyl myristate, tween 80 and propylene glycol were identified as best. The emulsification zone was demonstrated by a ternary phase diagram, and compatibility was confirmed with Fourier-transformed infrared spectroscopy (FT-IR). The formulated SMEDDS were characterized for robustness to dilution, globule size (GS), polydispersity index (PDI), viscosity, in-vitro dissolution and diffusion study, and drug release kinetics study. All the batches (A1-A9) passes the test and A3 was selected as an optimized batch that doesn't show phase separation, precipitation with globule size (101 nm), PDI (0.319), drug content (99.14±0.35 %), viscosity (10.71±0.02 mPa), self-emulsification time (46 sec), in-vitro drug release (98.25±0.22 %) within 8 h, release kinetics (Higuchi) and effective antidepressant in in-vitro diffusion studies. An optimized batch A3 observed circular in shape estimated by Transmission electron microscopy (TEM) and passes all the thermodynamic stability testing with loss of 0.271 mg of the drug after 90 days and showed marked antidepressant action with higher stability.

Design of Hydrogel for the Drug Delivery of Less Permeable Ursolic Acid Isolated from Rhododendron arboreum Flower in Animal Skin Membrane

Ursolic acid (UA) is a pentacyclic triterpene that has antioxidant, anticancer, and anti-inflammatory properties. As it belongs to the biopharmaceutical classification system IV due to its poor water solubility and permeability restricts its use in clinical application. So, the research is focused on the development of hydrogel containing encapsulated liposomes of ursolic acid to increase its permeability. The ursolic acid liposomal gel was prepared with a 0.5%, 1%, and 1.5% mixture of carbopol 934P and HPMC K4M as gelling agents. The pH and spreadability of liposomal gel were found to be in the range of (6.93±0.035 to 7.12±0.03) and (15.41±0.36 to 24.47±0.90) g.cm/sec respectively. The drug content was found to be in (19.77±0.02 to 20.11±0.02)%. The study of drug release kinetics showed Higuchi release followed by a non-Fickian diffusion mechanism. The result of the permeation study by Franz diffusion cell showed 1.55 times higher compared to the plain gel at the 5th hour of the study with a flux value of 0.455(mg/cm2/hr). It resolved the fast and enhanced delivery of liposomal ursolic acid through the skin membrane.

Comprehensive strategy of white analytical chemistry and analytical quality by design to sensitive spectrofluorimetric method for in-vitro drug release kinetic study of Ibrutinib-loaded nanostructured lipid carriers for leukemia via lymphatic targeting

Ibrutinib (IBR) is a drug classified as BCS class II, characterized by low solubility and high permeability. However, its oral bioavailability is limited to a mere 2.9% due to significant first-pass metabolism. To address this challenge, researchers developed IBR-NLCs (Nanostructured Lipid Carriers) using a DoE-based hot melted ultrasonication method to enhance its bioavailability and drug release profile. While various methods exist for IBR analysis in pharmaceutical formulations, human plasma, and rat plasma, a sensitive spectrofluorimetric method has not been reported for estimating IBR. To facilitate in-vitro drug release kinetic studies of IBR-NLCs, a sensitive and green spectrofluorimetric method was developed, combining principles of white analytical chemistry and analytical quality by design. This approach included a fractional factorial design for screening of method variables and a Box-Behnken design for method optimization. The developed method underwent rigorous validation following ICH guidelines. The developed method was applied to assess the in-vitro drug release kinetic study of IBR-NLCs in comparison to marketed formulations. Remarkably, the optimized IBR-NLCs exhibited sustained release of IBR which helps to decrease dose and dose frequency. The whiteness and greenness profiles of published and proposed method have been assessed using analytical greenness calculator, green analytical procedure index software, national environmental method index standards, and eco-scale assessment tool. The results confirmed that the proposed method is sensitive, eco-friendly, cost-effective, speedy, and user-friendly, making it an excellent choice for IBR estimation in NLCs. In summary, the developed method for drug release kinetic study of BR-NLCs, utilizing principles of white analytical chemistry and analytical quality by design, has not only improved drug release profile but also resulted in an efficient and environmentally friendly analytical approach.

Formulation and Evaluation of Teneligliptin Nanosuspension

In this present study, the drug Teneligliptin is selected for the management of Type-2 Diabetes mellitus. The drug-excipient compatibility study results showed that there is no chemical change occur between the drug and the excipients and there was no functional group change observed. Teneligliptin is poorly water-soluble drug and it was fabricated as nanosuspension of Nine formulations by using nano precipitation technique. In this method, nano size particle size of Teneligliptin was obtained by using different type of various proportions of stabilizers along with other ingredient at different stirring speed. For the prepared formulation (F1-F9) the particle size, polydispersibility index and zeta potential were done. Among nine formulations, formulation 8(F8) results revealed that the values are desirable and stable. The total drug content of all the formulation ranges from 81% to 99%, The average particle size of F1 to F9 batches was found to be in the range of 0.211 nm to 0.486 nm The scanning electron microspore study stated that the nano size particles were spherical in shape. Among all the formulations (F8) was optimized which showed maximum highest percentage of drug release at 24 hours. The cumulative percentage of drug release of formulation 8 (F8) increase with the optimum concentration of stabilizers and tween 80. The release rate of optimized formulation 8(F8) was fitted with various release kinetic studies and the selected formulation followed zero order kinetics. The results of stability study was confirmed that the prepared Teneligliptin nanosuspension is stable during the stability study. Thus, it can be concluded that the nanosuspension method was commercially feasible and cost effective.

Auricularia auricula Anionic Polysaccharide Nanoparticles for Gastrointestinal Delivery of Pinus koraiensis Polyphenol Used in Bone Protection under Weightlessness.

Auricularia auricula polysaccharides used in Pinus koraiensis polyphenol encapsulation and delivery under weightlessness are rarely reported. In this study, an anionic polysaccharide fragment named AAP Iα with a molecular weight of 133.304 kDa was isolated and purified to construct a polyphenol encapsulation system. Nanoparticles named NPs-PP loaded with a rough surface for Pinus koraiensis polyphenol (PP) delivery were fabricated by AAP Iα and ε-poly-L-lysine (ε-PL). SEM and the DLS tracking method were used to observe continuous changes in AAP Iα, ε-PL and PP on the nanoparticles' rough surface assembly, as well as the dispersion and stability. Hydrophilic, monodisperse and highly negative charged nanoparticles can be formed at AAP Iα 0.8 mg/mL, ε-PL 20 μg/mL and PP 80 μg/mL. FT-IR was used to determine their electrostatic interactions. Release kinetic studies showed that nanoparticles had an ideal gastrointestinal delivery effect. NPs-PP loaded were assembled through electrostatic interactions between polyelectrolytes after hydrogen bonding formation in PP-AAP Iα and PP-ε-PL, respectively. Colon adhesion properties and PP delivery in vivo of nanoparticles showed that NPs-PP loaded had high adhesion efficiency to the colonic mucosa under simulated microgravity and could enhance PP bioavailability. These results suggest that AAP Iα can be used in PP encapsulation and delivery under microgravity in astronaut food additives.

Experimental Design Modelling and Optimization of the Intercalation of Levofloxacin and Salicylic Acid into the Structure of ZnAl-LDH by Response Surface Method: in vitro Study of Release Kinetics, Antibacterial and Anti- Inflammatory Activities

In recent years, solid-state engineering has emerged as a promising method for improving the stability and potency of antibiotics and anti-inflammatory drugs. This study focuses on the design and optimization of the intercalation of levofloxacin (an antibiotic drug) and salicylic acid (an anti-inflammatory drug) into zinc-aluminium-layered double hydroxide galleries using response surface method. Release studies revealed that a burst release phenomenon was observed at the beginning of the release assay, and the pH value (in the range of 5.8-7.4) had very little influence on the levofloxacin and salicylic acid release efficiency. This indicates that zinc-aluminium-layered double hydroxide could be an effective inorganic carrier for levofloxacin and salicylic acid over a wide range of pH values. Four kinetic models were used to study the release kinetics and the drug release mechanism was also discussed. In addition, the intercalation of levofloxacin and salicylic acid into zinc-aluminium-layered double hydroxide exhibited enhanced antibacterial activity against Gram-positive Bacillus subtilis. The cell viability assay revealed non-toxic behavior of levofloxacin and salicylic acid intercalated into zinc-aluminium-layered double hydroxide against the monocyte/macrophage-like cell line.

Formulation and evaluation of Glibenclamide loaded Nanosponges

Nanotechnology mediated drug delivery has been reported to enhance the drug efficacy, bioavailability, reduced toxicity and improve patient compliance by targeting the cells and tissues to elicit the desired pharmacological action. The main aim of the study was to formulate Glibenclamide loaded nanosponges and to evaluate them. Glibenclamide loaded nanosponges were prepared by Emulsion solvent diffusion method using different polymers (Ethyl cellulose, β- cyclodextrin, Hydroxy Propyl β- cyclodextrin, Pluronic F68). The FTIR test is conducted as the preliminary test, by this test there was no interaction between the drug and polymers. Then nanosponges were evaluated for particle size, PDI, zeta potential, SEM, entrapment efficiency and invitro drug release. The particle size ranged from 640.7 to 876.2 nm, PDI ranged from 0.456 to 0.707, zeta potential from -17.3 to -34.3 mV and entrapment efficiency was ranged from76.21 to 98.23% The cumulative percentage release from all nanosponges varied from 80.35 to 97.56% after 12 hours depending upon the drug and polymers ratio and F5 formulation showed highest drug release i.e., 97.53%. The release kinetic studies showed that the release first order diffusion controlled and the n value (0.8769) from the Korsmeyer- Peppa’s model indicated the release mechanism was non-fickian type.

Design and Characterization of Mangiferin Sustained-Release Tablets

Background: Mangiferin is a natural bioactive compound used for various pharmacological activities like antidiabetic, anticancer, and anti-inflammatory. Objective: The development of unique sustained-release matrix tablets of mangiferin is the purpose of the work that is being presented here. Method: In this study, an effort is made to formulate mangiferin sustained-release matrix tablets by combining the sustained-release polymers HPMC K100M, Kollidone@SR, Keltone LVCR. Mangiferin matrix tablets have been synthesized by wet granulation utilizing the lactose works as the diluent. Systems were developed with different polymer percentages. Results: Refine the design based on observed differences in weight, hardness, thickness, percent friability, percent drug content, and in-vitro drug release. In-vitro release trials conducted by utilizing a USP type II device utilizing a 6.8 pH phosphate buffer as the separation medium revealed that the most successful F2 formulation, which included 20% polymer, was capable of supporting the mangiferin release for a time of 12 hours period. This sample showed the greatest coefficient (R) value in the Hixson-Crowell model, and release kinetics studies showed that this sample exhibited an erosion process and followed zero-order kinetics. Conclusion: We can conclude that Kollidone@Sr can be used to prepare sustained-release mangiferin.

Insight into the availability and desorption kinetics of Se and Cd in naturally-rich soils using diffusive gradients in thin-films technique

Cadmium (Cd) contamination of selenium (Se)-rich soils may jeopardize the nutritional benefits of Se-biofortified crops. This study employed diffusive gradients in thin-films (DGT) technique and DIFS (DGT-induced fluxes in soils) model to understand the interdependency and driving factors of Se and Cd distribution and desorption kinetics across 50 soils from south China with naturally elevated levels. DGT-labile Se was the highest (up to 2.66 μg L−1) in non-carbonate/shale-derived soils, while Cd was maximal (5.53 μg L−1) in carbonate-based soils, reflecting soil background concentrations and soil characteristics. Over one-third of the soils showed labile Se:Cd molar ratio below 0.7, suggesting Cd phytotoxicity risks. The DIFS-derived response times (Tc) and desorption rate constants (k−1) suggested that Se was resupplied to the soil solution faster than Cd in soils with higher pH and SOM level, but Se resupply was still restricted due to the rapid depletion of its labile pool. As the first study of Se and Cd release kinetics in soils, our results reveal dependence on soil parent materials, with low labile Se:Cd soils presenting greater Cd hazards. By elucidating Se and Cd lability and interactions in soils, our findings help to inform management strategies to balance reduced Cd risk with adequate Se availability.

Kinetic modelling of ultrasound-triggered chemotherapeutic drug release from the surface of gold nanoparticles

Therapeutic ultrasound can be used to trigger the on-demand release of chemotherapeutic drugs from gold nanoparticles (GNPs). In the previous work, our group achieved doxorubicin (DOX) release from the surface of GNPS under low-intensity pulsed ultrasound (LIPUS) exposure. However, the specific release kinetics of ultrasound-triggered DOX release from GNPs is not known. Here, we present a release kinetics study of DOX from GNPs under ultrasound exposure for the first time. A novel dialysis membrane setup was designed to quantify DOX release from LIPUS-activated GNPs at 37.0 °C and 43.4 °C (hyperthermia temperature range). Contributions of thermal and non-thermal mechanisms of LIPUS-triggered DOX release were also quantified. Non-thermal mechanisms accounted for 40 ± 7% and 34 ± 5% of DOX release for 37.0 °C and 43.4 °C trials, respectively. DOX release under LIPUS exposure was found to follow Korsmeyer–Peppas (K–P) kinetics, suggesting a shift from a Fickian (static) to a non-Fickian (dynamic) release profile with the addition of non-thermal interactions. DOX release was attributed to an anomalous diffusion release mechanism from the GNP surface. A finite element model was also developed to quantify the acoustic radiation force, believed to be the driving force of non-thermal DOX release inside the dialysis bag.

Abstract A031: Development of poly lactic acid based biodegradable nanoparticles for co-delivery of pirarubicin and gemcitabine for synergistic anti-tumor efficacy

Abstract Nanoparticles based drug delivery systems have provided a befitted solution for the poor pharmacokinetic properties and systemic toxicity caused by the chemo drugs because of their ability to improve bioavailability of the drugs at the desired site and thereby decreasing extracellular toxicity. The present work investigates the single or dual chemo drugs loaded PLA-based biodegradable polymeric nanoparticles for improved anti-tumor efficacy as compared to free drug formulations. For the study, an amphiphilic block copolymer; mPEG PLA has been synthesized and characterized using Gel permeation chromatography (GPC) for its molecular weight and poly dispersity index as well as with Nuclear magnetic resonance (NMR) and Fourier-transform Infrared (FT-IR) spectroscopies. Thereafter, two different chemo drugs Pirarubicin (PIRA, THP analogue of Doxorubicin) and Gemcitabine (GEM) have been chemically conjugated individually to mPEG PLA block copolymer via a linker molecule, Levulinic acid to give an acid labile polymer-drug conjugate and the % drug conjugation efficiency has been calculated using High performance liquid chromatography (HPLC). The synthesized polymer-drug conjugates have been employed to prepare PIRA/GEM single or dual-loaded nanoparticles via nanoprecipitation technique and the physiochemical properties including size, zeta potential, and stability were analyzed using Dynamic Light Scattering (DLS) and High-resolution transmission electron microscopy (HR-TEM). To carry out toxicity assessment of the mPEG PLA nanoparticles, both cytocompatibility and hemocompatibility were checked using MTT assay and Hemolysis assay respectively. Moreover, the cellular internalization studies of dye-loaded mPEG PLA nanoparticles were done using Confocal microscopy on SUM-149, breast cancer cells.  Besides, the drug release kinetic studies of the free PIRA/GEM from the PIRA/GEM single or dual-loaded nanoparticles were carried out in different pH environments; pH 7.4 and pH 5.0. The in-vitro cell proliferation inhibition studies of PIRA/GEM or dual-loaded nanoparticles were carried out on different human and murine breast cancer cell lines including MCF-7, MDA-MB-468, SUM 149, MDA-MB-231 and 4T1 and half-maximal inhibitory concentrations (IC50 values) were compared to that of respective free drug formulations. The overall results suggested that the prepared sub-nano sized PIRA/GEM single or dual-loaded particles are highly stable, uniformly spherical in size and biocompatible in nature. They were found to possess high cellular uptake, sustained drug release rate and synergistic efficacy and potential against both human and murine breast cancer cells in-vitro conditions. Citation Format: Priya Gupta. Development of poly lactic acid based biodegradable nanoparticles for co-delivery of pirarubicin and gemcitabine for synergistic anti-tumor efficacy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A031.

Enhancing encapsulation of filarial antigen Brugia malayi thioredoxin in nano-liposomes: The role of lecithin composition

Background and purpose: Lymphatic filariasis is a debilitating infectious disease prevalent in endemic areas, necessitating the development of an effective vaccine for eradication. Although recombinant vaccine candidates have been deemed safe, they often fail to provide sufficient protection, which can be overcome by encapsulating them in nano-liposomes. In this study, we have optimised the liposomal composition for enhanced stability and encapsulation of filarial antigen Brugia malayi thioredoxin (Bm-TRX). Experimental approach: Nano-liposomes were prepared using egg phosphatidylcholine (EPC) and cholesterol via thin-film hydration, followed by sonication and characterizing. Encapsulation efficiency was optimised using different weight ratios of EPC to cholesterol (8:2, 7:3, and 6:4) and total lipid (EPC+Cholesterol) concentration to antigen Bm-TRX (10:1, 10:2, and 10:3) followed by release kinetics study. Key results: Optimised parameters yielded spherical liposomes measuring 209 nm in diameter with narrow polydispersity. Our findings demonstrated the highest encapsulation efficiency of 70.685 % and stability of 10 hours for an EPC to cholesterol weight ratio of 7:3. The in silico study proved the antigenic nature of TRX. Conclusion: The liposomal formulations loaded with TRX, as optimized in this study, hold promise for improving antigen efficiency by enhancing stability, bioavailability, and prophylactic effects by acting as immune potentiators.

Formulation and evaluation of solid lipid nanoparticles of naringin to enhance its bioavailability

The objective of the present work was to formulate solid lipid nanoparticles loaded with naringin for improving the bioavailability of naringin. The SLNs loaded with naringin were prepared by using different ratio of palmitic and stearic acid as the lipids and Tween 80 as the surfactant. The method nanoprecipitation was used for preparation of the SLNs. The surfactant (Tween 80) helps in steric stabilization of the SLNs. The size range of SLNs obtained on sonicating for 7 was found to be 429 ± 76 nm when stearic acid was used and 365 ± 28 nm when palmitic acid was used for the preparation of SLNs. The zeta potential of all the SLNs ranged from -16 to -27 mV suggesting a stable formulation. The percentage of drug incorporated during nanoparticle preparation was determined by centrifuging the drug loaded nanoparticles at 15,000 rpm for 15 min and separating the supernatant. The highest encapsulation of naringin (71.7 ± 8.6 %) was obtained when the concentration of palmitic acid was 0.14 mmol. The in vitro release of naringin from the SLNs was measured by dialysis method using simulated gastric fluid as the dissolution medium. In vitro release kinetics studies for naringin loaded SLNs exhibited a sustained release pattern. Sustained release was observed over a period of 3 days. The stability of NSLN-7 was studied by storing at 4 ± 1 °C for 30 days. The particle size remained stable at the end of the study with drug entrapment of 71.5 %. This suggests that the SLNs prepared are stable on storage.

DEVELOPMENT AND EVALUATION OF DOXORUBICIN ANCHORED PLGA NANOPARTICLES AGAINST BREAST CANCER

The objective of this work was to design and develop Poly (D, L-Lactide-co-glycolide) (PLGA) nanoparticles (NPs) of Doxorubicin for the effective treatment of breast cancer. The nanoparticles (NPs) were optimized by applying a Box-Behnken design (BBD) using Design-Expert® Software and prepared using the double emulsification and precipitation method. Three independent factors such as PLGA 50:50 (A), PVA (B), stirring speed (C) were considered. Three dependent responses included entrapment efficiency (Response 1), particle size (Response 2) and Doxorubicin release at 10th hour (Response 3). ATR and DSC studies indicated compatibility between the drug and polymer. The morphological studies performed by SEM showed uniform and spherical shaped discrete particles with smooth surface and in a size range of 282.6 nm. X-ray diffraction was performed to confirm the crystalline nature of the drug after encapsulation. The NPs exhibited a zeta potential of 21.6 mV. In vitro release studies showed a drug release up to 10 hrs. The release kinetics study indicated first order kinetics while the release mechanism followed Higuchi model. The cell viability was found to be more than 80% after incubation with the DOX NPs for 24 h up to a concentration of 80 μg/ml. The DOX NPs treated MCF-7 displayed intrinsic cell damage and cell shrinkage as compared to the control group. It may be concluded from the present investigation that PLGA NPs bearing doxorubicin can effectively treat the breast cancer

Mevacor/Poly(vinyl acetate/2-hydroxyethyl methacrylate) as Solid Solution: Preparation, Solubility Enhancement and Drug Delivery.

Mevacor/Poly(vinyl acetate-co-2-hydroxyethyl methacrylate) drug carrier systems (MVR/VAC-HEMA) containing different Mevacor (MVR) contents were prepared in one pot by free radical copolymerization of vinyl acetate with 2-hydroxyethyl methacrylate using an LED lamp light in the presence of camphorquinone as a photoinitiator and Mevacor as a drug filler. The prepared material was characterized by FTIR, 1H NMR, DSC, SEM and XRD methods. Different parameters influencing the efficiency in the Mecvacor-water solubility and the drug delivery of this system, such as the swelling capacity of the carrier, the amount of Mevacor loaded and the pH medium have been widely investigated. The results obtained revealed that the Mevacor particles were uniformly dispersed in their molecular state in the copolymer matrix forming a solid solution; the cell toxicity of the virgin poly(vinyl acetate-co-2-hydroxy ethyl methacrylate) (VAC-HEMA) and MVR/VAC-HEMA drug carrier system exhibited no significant effect on their viability when between 0.25 and 2.00 wt% was loaded in these materials; the average swelling capacity of VAC-HEMA material in water was found to be 45.16 wt%, which was practically unaffected by the pH medium and the solubility of MVR deduced from the release process reached more than 22 and 37 times that of the powder dissolved directly in pH 1 and 7 media, respectively. The in vitro MVR release kinetic study revealed that the MVR/VAC-HEMA system containing 0.5 wt% MVR exhibited the best performance in the short gastrointestinal transit (GITT), while that containing 2.0 wt% is for the long transit as they were able to considerably reduce the minimum release of this drug in the stomach (pH1).

Nedaplatin/Peganum harmala Alkaloids Co-Loaded Electrospun, Implantable Nanofibers: A Chemopreventive Nano-Delivery System for Treating and Preventing Breast Cancer Recurrence after Tumorectomy.

Currently, the main pillars in treating breast cancer involve tumorectomy pursued by hormonal, radio, or chemotherapies. Nonetheless, these approaches exhibit severe adverse effects and might suffer from tumor recurrence. Therefore, there is a considerable demand to fabricate an innovative controlled-release nano-delivery system to be implanted after tumor surgical removal to guard against cancer recurrence. In addition, combining platinum-based drugs with phytochemicals is a promising approach to improving the anticancer activity of the chemotherapeutics against tumor cells while minimizing their systemic effects. This study designed polycaprolactone (PCL)-based electrospun nanofiber mats encapsulating nedaplatin (N) and Peganum harmala alkaloid-rich fraction (L). In addition to physicochemical characterization, including average diameters, morphological features, degradation study, thermal stability, and release kinetics study, the formulated nanofibers were assessed in terms of cytotoxicity, where they demonstrated potentiated effects and higher selectivity towards breast cancer cells. The dual-loaded nanofiber mats (N + L@PCL) demonstrated the highest antiproliferative effects against MCF-7 cells with a recorded IC50 of 3.21 µg/mL, as well as the topmost achieved selectivity index (20.45) towards cancer cells amongst all the tested agents (N, L, N@PCL, and L@PCL). This indicates that the dual-loaded nanofiber excelled at conserving the normal breast epithelial cells (MCF-10A). The combined therapy, N + L@PCL treatment, resulted in a significantly higher percent cell population in the late apoptosis and necrosis quartiles as compared to all other treatment groups (p-value of ≤0.001). Moreover, this study of cell cycle kinetics revealed potentiated effects of the dual-loaded nanofiber (N + L@PCL) at trapping more than 90% of cells in the sub-G1 phase and reducing the number of cells undergoing DNA synthesis in the S-phase by 15-fold as compared to nontreated cells; hence, causing cessation of the cell cycle and confirming the apoptosis assay results. As such, our findings suggest the potential use of the designed nanofiber mats as perfect implants to prevent tumor recurrence after tumorectomy.