Emulsion Solvent Evaporation Method Research Articles

Formulation and Evaluation of Topically Retained Hydrogels Loaded with Timolol Maleate Microspheres for Extended Release in Treating Glaucoma

Conventional aqueous eye drop formulations have a shorter retention period and wash out of the precorneal region more easily. In this study, biodegradable microsphere-loaded hydrogels were developed to extend the time of residence and improve the drug bioavailability. The prepared microspheres were fabricated using PLGA as the biodegradable polymer and PVA as the surfactant. Hydrogels were prepared using Carbopol 940 and Gellan gum as gelling agents. Methods: The microspheres were created through a technique known as double emulsion solvent evaporation method. Evaluation included for its percentage yield, entrapment efficiency, particle size and surface morphology of the prepared microspheres. Timolol Maleate microsphere loaded hydrogel underwent assessments for pH, spreadability, rheological behaviour, sterility, antimicrobial efficacy, in vitro release studies, drug release kinetics and ocular irritation. Results: FTIR analysis confirmed compatibility between the drug and polymer. SEM observations indicated spherical microspheres with sizes ranging from 1 to 12 µm, suitable for ocular application. All formulations exhibited pH values between 4.2 and 5.0, with gelation occurring at 35°C to 38°C. Formulation F3 demonstrated optimal viscosity (1486 – 1850 cps) and good spreadability. Sterility tests were successful, and F3 displayed a drug release of 82.6% after 24 hours. Antimicrobial studies exhibited inhibition zones, and ocular tests on rabbits revealed no irritation. Stability analysis indicated no significant changes in pH or clarity. Conclusion: Based on physiological, rheological, and in vitro evaluations F3 was identified as the most suitable formulation for extended Timolol Maleate release via hydrogel, holding promise for effective glaucoma treatment.

Optimizing the formulation variables for encapsulation of linezolid into polycaprolactone inhalable microspheres using double emulsion solvent evaporation

Inhaled antibiotics delivered through dry powder inhalers (DPIs) effectively treat severe bacterial infections by directly targeting the lungs. Our study focused on developing inhalable dry powder microspheres of linezolid (LNZ) using biodegradable polycaprolactone (PCL) polymer. The LNZ-PCL microspheres were fabricated using a double emulsification solvent evaporation method. Optimization of formulation parameters was performed using a factorial design. Evaluation of the microspheres included size, shape, drug loading, entrapment efficiency, aerosolization, and drug release. The morphological analysis confirmed spherical-shaped rough particles within the inhalable size range. The encapsulation efficiency was determined to be 52.84%, indicating successful drug incorporation. Aerosolization efficiency was significantly enhanced when LNZ-PCL microspheres were combined with lactose as a carrier, achieving a fine particle fraction (FPF) value of 70.90%. In-vitro dissolution studies demonstrated sustained drug release for over 24 h under lung pH conditions. Overall, our study highlights the potential of inhalable LNZ-PCL microspheres as a targeted approach for treating pulmonary tuberculosis. Further research and in-vivo studies are needed to validate their effectiveness in life-threatening bacterial infections.

Microencapsulation study of bioderived phase change material beeswax with ethyl cellulose shell for thermal energy storage applications

ABSTRACT The commercial shape-stabilized phase change material (PCM) products are obtained from synthetic raw materials. These materials are produced from carbon-intensive petroleum-refining processes. The carbon footprint can be minimized by using biobased products. Beeswax is a naturally available PCM with high phase transition enthalpy comparable to synthetic PCMs. In the previous literature studies, beeswax was shape-stabilized with synthetic materials. In the present study, beeswax was shape-stabilized with biopolymer ethyl cellulose by emulsion solvent evaporation method. The study aims to determine optimum microencapsulation process parameter levels for synthesizing microcapsules with high thermal energy storage (TES) capacity. The optimized process parameters for formulating microcapsules were 60:40 core/shell ratio, 2% PVA concentration, ethyl acetate solvent, and 40°C evaporation temperature. The microcapsules prepared with optimized process parameters were characterized using differential scanning calorimeter (DSC), T-history analysis, Fourier transform infrared (FTIR) spectroscope, and scanning electron microscope (SEM). FTIR and SEM analysis confirmed ethyl cellulose shell formation over the beeswax core. The optimized MPCM formulation possesses 115.8 J/g melting enthalpy with peak phase transition temperature of 58.2°C and thermal conductivity of 0.219 W/mK. The porous structure of the shell reduced melting enthalpy of optimized MPCM formulation to 84.6 J/g after 50 thermal cycles. The synthesized microcapsules comprise sustainable materials and have high TES capacity. The fabricated microcapsules can be used as TES additive in composite and coating formulations in food packaging.

Formulation and Evaluation of Colon Targeted Ciprofloxacin Microspheres

In the present study, Colon-targeted Ciprofloxacin hydrochloride microspheres were formulated and their in vitro properties were assessed to determine whether or not the antibiotic could be delivered to the colon. By utilizing span-80 as an emulsifying agent, ciprofloxacin hydrochloride microspheres for colon targeting were prepared using the emulsion-solvent evaporation method. According to the preliminary trial findings, the ratio of drug to polymer had an impact on the microspheres' properties. The Ciprofloxacin: Eudragit S-100+HPMC 6cps ratio of 1:1, 1:2, 1:3, 1:4, 1:5, and 1:6 were used to make the colon targeting microspheres, in which the ratio of Eudragit S-100 to HPMC was always 1:1. The combination of Eudragit S-100 and HPMC demonstrated increased release lag time and regulated release rate, which improved protection of the drug-containing core. For the majority of the formulations examined, zero-order release followed a time delay caused by the hydrogel's swelling/retarding behaviour before the medication started to come out of the microspheres. The colon-targeting microspheres were also tested for micrometrics, particle size and surface properties, percentage drug content, encapsulation effectiveness, and in vitro drug release study in the three different pH environments (0.1 N HCL, Phosphate buffer pH 6.8 and Phosphate buffer pH 7.4) for 12 hours. The kinetics of drug release in vitro and the drug release mechanism of the microspheres were further investigated. With a particle size of 58.9 m, an almost spherical shape, and free-flowing characteristics, the best formulation batch had the highest drug entrapment efficiency of 86.81%. It was followed by a zero-order rate release with a non-fiction-diffusion mechanism, which had an 82.77% drug release rate.

Design of experiments approach for the development of a validated method to determine the exenatide content in poly(lactide-co-glycolide) microspheres

Due to the lack of pharmacopeia guidelines for injectable microspheres based on poly (D, L-lactide-co-glycolide) (PLGA), an internal method validation is a critical prerequisite for quality assurance. One of the essential issues of developing peptide-based drugs loaded PLGA microspheres is the precise determination of the amount of peptide drug entrapped in the microspheres. The aim of this study is the development and optimization of a method for measuring the drug content loading of PLGA microspheres using exenatide as a model peptide drug. Exenatide-loaded PLGA microspheres were prepared by a double emulsion solvent evaporation method. The extraction method to determine exenatide content in microspheres was optimized using Design of Experiments (DoE) approach. After the initial screening of six factors, using Fractional Factorial design (FFD), four of them, including type of organic solvent, buffer/organic solvent ratio (v/v), shaking time and pH, exhibited significant effects on the response, namely the exenatide loading, and a Box-Behnken design (BBD) was subsequently applied to obtain its optimum level. The optimum level for organic solvent volume, buffer/organic solvent ratio, shaking time, and pH were 4 ml, 1, 5.6 hrs, and pH 6, respectively. The exenatide content in microspheres under these conditions was 6.4 ± 0.0 (%w/w), whereas a value of 6.1% was predicted by the derived equation. This excellent agreement between the actual and the predicted value demonstrates that the fitted model can thus be used to determine the exenatide content.

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Development and Optimization of Fluvastatin Sodium Loaded Biodegradable Microspheres

Fluvastatin sodium is a hypolipidemic agent that reduces cholesterol synthesis by inhibiting HMG-COA reductase. The drug has a comparatively short biological half-life (1.2 hours) and low bioavailability (24– 29%), making it an appropriate candidate for a sustained-release drug delivery system. This study aimed to formulate biodegradable microspheres of fluvastatin sodium by optimization through an experimental design approach. Microspheres containing fluvastatin sodium were prepared by o/w emulsification solvent evaporation method using poly (lactic-co-glycolic acid) (PLGA 50:50) as a biodegradable polymer. 32 full factorial design was applied to study the effect of drug to polymer ratio and stirring speed on dependent variables, i.e. particle size, entrapment efficiency, Q1h, t80%. Prepared formulations were subjected to evaluate physicochemical properties and release characteristics. DSC and FTIR proved no interaction between the drug and excipients. Microspheres possessed size in the range of 193 to 344 μm and entrapment efficiency varied from 63.1 to 85.6%. Formulations showed drug release up to 23% within 1-hour. while t80% was found in between 3–9 hours. Regression analysis and ANOVA results suggested a significant effect (p<0.05) of variables on responses. The results of the present study suggested that biodegradable microspheres of fluvastatin sodium prepared using poly (lactic-co-glycolic acid) can be a promising alternative for conventional delivery and suitable for sustained drug release.

Lipid-Polymer Hybrid Nanosystems: A Rational Fusion for Advanced Therapeutic Delivery.

Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid-polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core-shell nanoparticles, hollow core-shell nanoparticles, biomimetic lipid-polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core-shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core-shell-structured LPHNPs.

Potential analgesic effect of Foshousan oil-loaded chitosan-alginate nanoparticles on the treatment of migraine.

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2nm, 45.1 ± 6.2mV) had a well-defined spherical shape with prolonged drug release and good storage within 4weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15μg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.

Biocatalytic synthesis of new polyesteramides from ε-caprolactam and hydroxy acids: Structural characterization, biodegradability, and suitability as drug nanocarriers

The synthesis of polyesters and polyamides by enzyme-catalyzed processes in vitro was developed in the last decades as a green alternative to obtain biodegradable synthetic polymers with various applications, such as nanoparticle-sized carriers for drug delivery. Polyesteramides were much less studied in this respect, although having the presumable advantage of increased mechanical and thermic resistance brought by the amide moieties. In this work, polyesteramides were synthesized for the first time employing as raw materials ε-caprolactam and a hydroxy acid. L-malic, 3-hydroxybutyric, 12-hydroxystearic and 16-hydroxyhexadecanoic acid, respectively, were investigated as co-monomers in solventless or organic medium, using the immobilized lipase Novozyme 435 as catalyst. The short chain hydroxy acids holding secondary hydroxyl groups yielded oligomers with average degree of polymerization no higher than 4, while in the case of the long-chain 12-hydroxystearic acid this value increased to 7. The best results were achieved by using 16-hydroxyhexadecanoic acid in 2:1 M excess at 80 °C, yielding a product with 75% copolymer content and average molecular weight higher than 3000 Da. The emulsion-solvent evaporation method allowed the efficient production of nanoparticles based on this copolymer, with sizes around 230 nm, used for the encapsulation of a model bioactive compound, the anticancer drug sorafenib. Production yields of >70% and encapsulation efficiencies of around 60% are very promising for further development of this approach.

Preparation and 3D printability study of bio-based PBAT powder for selective laser sintering additive manufacturing

Additive Manufacturing (AM) has been recognized as a highly versatile manufacturing method with high potentiality. Polymers are materials of central importance for AM specifically for fabrication of original and customized parts. However, most of the polymers currently in use derive from fossil sources, which extensive use represents a critical issue for the environment. This scenario encourages the use of sustainable and biodegradable biopolymers. The present paper focuses on the study of the printability of a bio-based powder, starting from an aromatic‐aliphatic biodegradable polyester, poly (butylene adipate-co-terephthalate) (PBAT), as sustainable alternative for Selective Laser Sintering (SLS) conventional materials. Bio-based polymers represent environmentally friendly materials that can be suitable for AM, although several problems still need to be solved for SLS applications. In fact, it is challenging to produce polymeric powders with specific particle size and size distribution, spherical shape, good flowability and processability. From this point of view, PBAT powder was prepared by means of an emulsion solvent evaporation method, characterized from morphological and thermal points of view, and then successfully used for SLS process, with the aim to obtain novel 3D printed objects using for the first time this biodegradable polymer.

Fabrication of PLGA Nanoparticles Using Combination of PCL-PVA-PEG Copolymer as Surfactant: In-Vitro Characterization and Cytotoxicity Study

Objective: The present study aimed to fabricate Poly lactic acid co-glycolic acid (PLGA) nanoparticles loaded with resveratrol using a novel graft co-polymer surfactant named Soluplus®. Methods: The PLGA nanoparticles were prepared in the present study using polyvinyl caprolactam polyvinyl acetate polyethylene glycol amphiphilic graft copolymer named Soluplus® as surfactant through double emulsification and single emulsification-solvent evaporation method. The formulations were prepared successfully to encapsulate the drug resveratrol, and then evaluated for their particle size, polydispersity index, zeta potential, drug loading and the degree of entrapment of the drug. A scanning electron microscope was used to examine the morphology of the nanoparticles. In vitro drug release was assessed and, mathematical pharmacokinetic modelling was done to assess the release pattern. A comparative cytotoxicity study between free drug and prepared nanoparticles using MTT assay was carried out for cell viability evaluation. Uptake and internalization of nanoparticles were also studied using confocal fluorescence microscopy. Results: The results demonstrated successful fabrication of the PLGA nanoparticles using the Soluplus as polymer surfactant. The drug, polymer and the all the excipients were found to be compatible and did not indicate any interaction. The results also indicated the prepared nanoparticles (SF2) as suitable resveratrol delivery vehicle in terms of the compliant particle size (344.6 ±6.63 nm), polydispersity index (0.962), zeta potential (- 18.5±1.21), drug loading (18.94± 0.27%), the entrapment efficiency (39.62±0.17%) and drug release (75.13±0.17%). The shape and surface morphology of the formulated nanoparticles were found to be spherical and smooth. Cytotoxicity study also demonstrated significant reduction of cell viability by the nanoparticle compared to free resveratrol. The highest cytotoxicity of SF2 against MCF7 cell was found in 2000 nM concentration with 3.03±0.05 percent of cell viability. It was found that the percentage of growth inhibition was increasing with increasing concentration of SF2 and IC50 value of this assay was 108.94 μg/ml. Conclusion: It has been found that the Resveratrol loaded PLGA nanoparticles were successfully formulated and found to perform better in terms of efficacy and cytotoxicity.

A Novel UHPLC-MS/MS-Based Bioanalytical Method Developed for S-Allyl Cysteine in the Establishment of a Comparative Pharmacokinetic Study

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs (S-Allyl Cysteine Poly (D,L-lactide-co-glycolic acid) Nanoparticles) were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency to be 5.13 ± 0.10% and 82.36 ± 4.01%, respectively. SC PLGA NPs showed a spherical morphology of an average size (134.8 ± 4.61 nm), PDI: 0.277 ± 0.004, and −25.3 ± 1.03 mV Zeta-Potential (ZP), and is suitable for oral delivery. The development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameter examinations with 1.219 min RT, MS (162.00/73.10), and a total run-time of 2.0 min. Additionally, 1.0–1000.0 ng/mL was a linear range with inter- and intra-day accuracy of 92.55–99.40%, followed by a precision of 1.88–4.23%. SC PLGA NP’s oral bioavailability was significantly higher (** p < 0.01) in comparison to the SC-S treated groups’ (iv and oral). The antimicrobial activity of SC PLGA NPs proved to be more effective than pure S-Allyl-L-Cysteine with significant results (p < 0.01) in comparison to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties, which can be helpful for oral administration. Based on the proposed research results, SC PLGA NPs were used for the improvement in oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

DoE Enabled Development and In-Vitro Optimization of Curcumin-tagged Cilostazol Solid Nano Dispersion

Background: Diabetes is a prevailing disease worldwide and its complications are also hazardous including nephropathy. Drug available to treat Diabetic Nephropathy (DN) faces bioavailability issues related to solubility and absorption of drugs. Cilostazol (CLT) is a BCS class II drug that is poorly water-soluble which affects its therapeutic efficacy. CLT reduces reactive oxy-gen species (ROS) increased in DN. Curcumin (Cur) is also hydrophobic but Cur has many therapeutic efficacies like anti-inflammatory and antioxidant properties that help for the treatment of DN. Objective: The objective of the current study was to develop and optimize the Cilostazol Solid Dis-persion Nanoparticle (SDN) to improve the bioavailability of the drug by tagging it with Cur by us-ing PVP VA S 630 as polymer and Poloxamer 407 as surfactant. Method: Different formulations were developed using the emulsion solvent evaporation method, PVP VA S 630 as the hydrophilic polymer, and Poloxamer 407 as a surfactant. Two-factor, three-level Box-Behnken Design (BBD) was used for statistical analysis of the selected process variable's main effect and interactive effect on the response. Curcumin tagging was also done for the entire batches. Nanoparticles were characterized by FT-IR spectroscopy, DSC, Particle size, Zeta poten-tial, Drug entrapment efficiency, Solubility, and % CDR studies. Results: Among the 17 different formulations (CLT1-CLT 17), with a solubility of 39.5 μg/ml, a % CDR of 99.55, a typical particle size of 219.67 nm with a PDI of 0.258, entrapment efficiency of 73.47%, and a -10.6 mV of Zeta potential, CLT-15 was optimized. To determine CLT and curcu-min, the simultaneous UV calibration method was created. Overall, the DSC study indicated the amorphous nature of the Nano Dispersion, which in turn means the successful entrapment of the CLT in the Nano Dispersion matrix. TEM images also confirmed the spherical nanoparticles. The optimized batch of drugs tagged with curcumin was compared with the plain drug Solid Dispersion Nanoparticles. Conclusion: Together with the molecules of curcumin, the solid nano dispersion of CLT was pro-duced, which will add to the benefits of the management of Diabetic Nephropathy. In the current study, we underline the importance of utilising both API and phytochemicals in the treatment of Di-abetic Nephropathy, and we anticipate further basic research or clinical trials to support innovative treatments. It is possible to use these matrix-forming polymers for active ingredients with poor sol-ubility, whether they are natural or synthetic. It has also been demonstrated that these carriers (PVP VA S 630 & Poloxamer) increase the dissolution rate (in-vitro).

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres.

Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.

Enhanced Cytotoxic Activity of 6-Mercaptopurine-Loaded Solid Lipid Nanoparticles in Hepatic Cancer Treatment.

6-Mercaptopurine (6-MCP) is an antiproliferative purine analog used in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and inflammatory bowel disease (Crohn's disease, ulcerative colitis). Although 6-MCP has the great therapeutic potential for cancer and immunosuppressant-related diseases, 6-MCP is not readily soluble in water, presents a high first-pass effect, short half-life (0.5-1.5 h), and implies a low bioavailability (16%). On the contrary, solid lipid nanoparticles (SLNs) are prepared from solid lipids at room temperature and body temperature. In this study, SLNs were prepared w/o/w double emulsion-solvent evaporation method using Precirol ATO5 as matrix lipid. In the emulsion stabilization, surfactant (Tween 80) and polymeric stabilizer (polyvinyl alcohol [PVA]) were used. Two group formulations using Tween 80 and PVA were compared in terms of particle size, polydispersity index, zeta potential encapsulation efficiency%, and process yield%. Differential calorimetric analysis and release properties were examined for optimum formulation, and release kinetics were calculated. According to studies, sustained release was obtained with SLNs by the Korsmayer-Peppas kinetic model. The in vitro cytotoxicity studies were performed on the hepatocarcinoma (HEP3G) cell line. According to the results, successful SLN formulations were produced, and PVA was found best stabilizer. Optimum formulation exhibited significantly higher cytotoxic effects on HEP3G than on pure 6-MCP. These results demonstrated that solid lipid nanodrug delivery systems have great potential for formulation of 6-MCP.

Lipase‐Responsive Rifampicin‐Based Biodegradable PCL Nanocarrier for Antibacterial Treatment

AbstractRifampicin (RFP) is a first‐line drug used to treat a variety of infections, including wound infections but has limitations in its use due to its toxicity. Hence, an urgent need exists for the development of suitable carriers for the delivery of the antibiotic. In this study, a novel approach is introduced for drug administration, employing stimulus‐responsive carriers to achieve an on‐demand strategy. This innovative method aims to minimize the dosage and frequency of drug administration, consequently lowering cytotoxicity levels. We used the lipases‐sensitive polycaprolactone (PCL) to produce nanocomposites loaded with rifampicin (PCL−RFP NPs). Nanoparticles were prepared by a single‐step emulsion solvent evaporation method. The size distribution of blank nanoparticles (PCL NPs) and PCL−RFP NPs were 172±30 nm and 229±58 nm, respectively. The liberation of RFP from PCL−RFP NPs was monitored over a period of 72 h in the absence and the presence of lipase was 9.46±0.24 % and 53.3±3.33 %, respectively, indicating responsive behavior. The minimum inhibitory concentration to lipase‐expressing Staphylococcus aureus (S. aureus) of PCL−RFP NPs was significantly improved compared to the free drug. Cytotoxicity tests using human dermal fibroblasts showed that the nanocomposites had better biocompatible when compared to the free drug. These findings indicate that the developed nanocomposite carriers have the potential to be promising candidates for delivering antibiotics in the field of biomedicine.

Effect of Surfactant on controlling the Size of Octadecylamine-based Solid Lipid Nanoparticles and Toxicity

Surfactants play a major role in solid lipid nanoparticles’ (SLNs) composition and properties, especially in terms of particle size and zeta potential. Not only the type of the surfactants but also their amounts and chemical compatibility with the lipid core within the formulation cause good changes. In this study, our goal was to determine the effect of tween 80 (a non-ionic surfactant) on octadecylamine (cationic lipid)-based SLN formulation and its influence on SLNs properties. Also, we examined the effect of sonication and filtration as mechanical forces on the particle size, zeta potential and PDI features. Five different formulations were performed by the emulsion solvent evaporation method. Particle size distribution, zeta potential and PDI values were determined by Zetasizer via the dynamic light scattering method. We obtained SLNs resulting from different formulations and one formulation was selected with the most suitable properties for further studies. The stability of the SLNs was examined by incubating them at 4 °C in the dark for particular time intervals and the results revealed not only minimal changes in particle size but also no significant changes in zeta potential and PDI values. The nanoparticles were characterized morphologically with Transmission electron microscopy (TEM) and Atomic force microscopy (AFM). The chemical characterization was performed by Fourier-transform infrared spectroscopy (FT-IR). In vitro cytotoxicity via MTT assay on L929 mouse fibroblast cell line was performed and cell viability was determined over 63% for all concentrations.

Dual receptor specific nanoparticles targeting EGFR and PD-L1 for enhanced delivery of docetaxel in cancer therapy

Dual-receptor targeted (DRT) nanoparticles which contain two distinct targeting agents may exhibit higher cell selectivity, cellular uptake, and cytotoxicity toward cancer cells than single-ligand targeted nanoparticle systems without additional functionality. The purpose of this study is to prepare DRT poly(lactic-co-glycolic acid) (PLGA) nanoparticles for targeting the delivery of docetaxel (DTX) to the EGFR and PD-L1 receptor positive cancer cells such as human glioblastoma multiform (U87-MG) and human non-small cell lung cancer (A549) cell lines. Anti-EGFR and anti-PD-L1 antibody were decorated on DTX loaded PLGA nanoparticles to prepare DRT-DTX-PLGA via. single emulsion solvent evaporation method. Physicochemical characterizations of DRT-DTX-PLGA, such as particle size, zeta-potential, morphology, and in vitro DTX release were also evaluated. The average particle size of DRT-DTX-PLGA was 124.2 ± 1.1 nm with spherical and smooth morphology. In the cellular uptake study, the DRT-DTX-PLGA endocytosed by the U87-MG and A549 cells was single ligand targeting nanoparticle. From the in vitro cell cytotoxicity, and apoptosis studies, we reported that DRT-DTX-PLGA exhibited high cytotoxicity and enhanced the apoptotic cell compared to the single ligand-targeted nanoparticle. The dual receptor mediated endocytosis of DRT-DTX-PLGA showed a high binding affinity effect that leads to high intracellular DTX concentration and exhibited high cytotoxic properties. Thus, DRT nanoparticles have the potential to improve cancer therapy by providing selectivity over single-ligand-targeted nanoparticles.

A convergent synthetic platform of hydrogels enclosing prednisolone-loaded nanoparticles for the treatment of chronic actinic dermatitis

ABSTRACT Recurrent eczematous lesions and acute itching describe chronic actinic dermatitis (CAD). Continuous use of corticosteroids might result in a dermal adverse effect. Chitosan (CS)-coated PLGA nanoparticles encapsulated prednisolone (PDS) and co-encapsulated to poloxamer hydrogel to enhance anti-inflammatory action and reduce side effects. The PDS@NPs were synthesized using the solvent-emulsification evaporation method, and their physical and chemical properties were analysed. Ex vivo drug absorption experiment was conducted utilizing the Franz diffusion cells in vitro. Toxic effects on human fibroblasts and keratinocytes were not observed in the nanoparticle formulations. Nanoparticles and hydrogels altered PDS’s release kinetics, but not by the non-encapsulated PDS (NE@PDS). Nanoparticles could not penetrate the stratum corneum of removed the skin, which shows the nano-encapsulation of PDS improved skin absorptions. Pseudoplastic and non-Newtonian behaviour was seen in all hydrogels. The nanoformulations appear to be a promising option for glucocorticoid delivery to individuals with chronic actinic dermatitis (CAD).