Emulsion Solvent Evaporation Research Articles

Definition of Design Space for Preparation and Stability of Tramadol Hydrochloride Loaded Nanoparticles Using OFAT Experiments for Infusion in Pain Management

AbstractThis paper presents an experimental study on preparation of tramadol hydrochloride (TrH) loaded nanoparticles, and stability determination in various infusion solutions. In this study, various nanoparticle preparation parameters based on w/o/w emulsification solvent evaporation method, including stabilizer type, stabilizer concentration, polymer concentration, homogenization speed and initial drug amount were systematically tested to verify their versatility for preparing nanoparticles. Initially both particle size and encapsulation efficiency of nanoparticles were changed significantly with the change in surfactant and polymer ratio (p<0.05). However, homogenization speed only changed particle size (average size 339.3±1.8 nm for 15000 rpm, 318.9±6.4 nm for 20000 rpm and 237.2±7.8 nm for 25000 rpm) (p<0.05) and initial drug concentration is only affected the encapsulation efficiency (34.2±0.7% for 4 mg/mL and 33.2±0.9 for 1.6 mg/mL) (p<0.05). Storage at room temperature for 3 months resulted in an increase in particle size and polydispersity index. Prepared nanoparticles showed the best stability after storage at – 20 °C for in 3 months. Finally, storage of nanoparticles in various infusion solutions resulted an undesirable changes for 6% Hydroxyethyl starch in 0.9% sodium chloride injection, 10% Dextran 40 and 4% Succinyl gelatin solutions. It was shown that an appropriate delivery of TrH loaded PLGA nanoparticles as infusion can be prepared only in water for injection, 20% Mannitol, 0.9% Sodium chloride and 5% Dextrose solutions.

PLGA nanocapsules as a delivery system for a recombinant LRP-based therapeutic.

Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age-related diseases. Recently, it has been found that overexpression of LRP-FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age-related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein-based drug synthesised using poly(lactic-co-glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification-solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK-293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age-related diseases.

Pioglitazone Nanoparticles Development, Characterization, Optimization, and a Zebrafish Model Evaluation of its Teratogenic Safety

Background: New nanoparticles (NPs) and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. Nanomaterials are materials with d50 value from 1 to 100nm. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. background: New nanoparticles and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. Objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes. objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes Methods: The emulsion solvent evaporation approach was used to create nanoparticles utilising HPMC K15M and Eudragit S100 as polymers, and Tween 80 as a surfactant. On framed nanoparticles, in-vitro evaluation approaches for drug-polymer compatibility, percentage yield, particle size, zeta potential, polydispersity index, surface morphology, encapsulation effectiveness, and in-vitro drug release study were used, followed by in-vivo acute toxicity experiment. Conclusion: From the obtained data, it can be said that a suitable optimized formulation of pioglitazone nanoparticles was prepared, which offered extended drug release of 95% in 10 hours.

Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer’s disease

Alzherimer’s disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood–brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Bioactive extracts from grape (Vitis vinifera L. cv. País) leaves: Characterization and encapsulation in poly-3-hydroxybutyrate-co-3-valerate microparticles

Vitis vinifera var. L. País leaf extract, previously characterized, was microencapsulated by emulsion-solvent evaporation method using two different procedures: the conventional dropwise and micromixer device. The poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) was used as encapsulating polymer. In addition, the effect of extraction time and ethanol:water ratio on the yield and the content of bioactive compounds of grape leaf extract obtained by Soxhlet method was determined using the face-centered central composite design. The highest bioactive compound were obtained using a 70:30 ethanol:water solvent ratio during 4 cycles. This extract is mainly composed of cinnamic acid, quercetin-3-glucoside and quercetin-3-glucorinide, containing 3.56, 2.08 and 1.19 mg g−1 extract, respectively. The total polyphenol content determined by Folin Ciocalteu method was 164 ± 14 mg GAE g−1 extract. The microparticles (2–3 μm) had spherical shape with rough and porous surface. The encapsulation efficiency was 15.1% and 60.6% for the PHBV microparticles prepared using conventional dropwise and micromixer device, respectively. The antioxidant activity present in the original extract was preserved around 50%–80% and 20%–70% in the loaded microparticles. The best results were achieved when grape leaf extract was encapsulated using micromixer device. The cell viability assay in 3T3-L1 fibroblasts, showed that loaded microparticles are not cytotoxic. In conclusion micromixer device showed to be effective for the microencapsulation of grape leaf extract using PHBV as encapsuling polymer.

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD). R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

Pesticide loaded nanohydrogel based on attapulgite and gelatin with improved foliar adhesion.

Pesticides have been widely applied to promote plant growth due to their high insecticidal efficiency. However, most pesticides easily slip from the leaf surface due to the low foliar adhesion, leading to significant damage to the environment and human health. Increasing foliar adhesion of pesticides has been a major challenge. Nanomaterial technology, which can deliver pesticide active ingredients, offers a new opportunity to increase pesticides efficacy with higher foliar adhesion. In this study, we prepared the pesticide loaded nanohydrogel ALP@Ge-g-P(AA-co-AM)/ATP by grafting attapulgite and gelatin onto P(AA-co-AM), and loading the pesticide alphacypermethrin synchronously via the emulsion solvent evaporation method. The size of the new nanohydrogel was 20.5 nm and the pesticide loading capacity was 21.5%. Compared to P(AA-co-AM), the water absorbency of Ge-g-P(AA-co-AM)/ATP increased by 54.3% in 120 min, while the water retention increased from 4.27% to 38.7% after 48 h. Washout experiments and contact angle results suggested that the nanohydrogel, with a contact angle of 44.8° indicating good wettability, can resist rain flush and increase foliar adhesion naturally. Overall, the preparation of pesticide loaded nanohydrogel is simple. Experiments demonstrated the pesticide loaded nanohydrogel has high efficiency and strong foliar adhesion. This makes it a promising candidate for spraying application and reducing pollution levels. © 2024 Society of Chemical Industry.

Magnetic Polystyrene Nanoparticles Prepared by Emulsion Solvent-Evaporation for the Chemiluminescent Immunoassay.

In clinical diagnosis, magnetic polystyrene nanoparticles (MPS NPs) are commonly applied to, e.g., the chemiluminescent immunoassay (CLEIA). However, the conventional preparation method of MPS NPs requires a long duration of heating to form polymer particles, which is inefficient. In this study, we prepared MPS NPs by emulsion solvent-evaporation without heating. We evaluated the effect of the solvent in the water and organic phases on the magnetic particle content. MPS NPs prepared by 4% (v/v) MeOH aqueous solution and adding stearic acid (SA) (4MeSA-MPS NPs) exhibited the highest magnetic particle content. Furthermore, CLEIA analysis indicates that the C-reactive protein detection limit is 80 pg/mL. Thus, 4MeSA-MPS NPs are promising for clinical diagnoses.

In vitro evaluation of physicochemical-dependent effects of polymeric nanoparticles on their cellular uptake and co-localization using pulmonary calu-3 cell lines

Objective The study evaluated physicochemical properties of eight different polymeric nanoparticles (NPs) and their interaction with lung barrier and their suitability for pulmonary drug delivery. Methods Eight physiochemically different NPs were fabricated from Poly lactic-co-glycolic acid (PLGA, PL) and Poly glycerol adipate-co-ω-pentadecalactone (PGA-co-PDL, PG) via emulsification-solvent evaporation. Pulmonary barrier integrity was investigated in vitro using Calu-3 under air-liquid interface. NPs internalization was investigated using a group of pharmacological inhibitors with subsequent microscopic visual confirmation. Results Eight NPs were successfully formulated from two polymers using emulsion-solvent evaporation; 200, 500 and 800 nm, negatively-charged and positively-charged. All different NPs did not alter tight junctions and PG NPs showed similar behavior to PL NPs, indicating its suitability for pulmonary drug delivery. Active endocytosis uptake mechanisms with physicochemical dependent manner were observed. In addition, NPs internalization and co-localization with lysosomes were visually confirmed indicating their vesicular transport. Conclusion PG and PL NPs had shown no or low harmful effects on the barrier integrity, and with effective internalization and vesicular transport, thus, prospectively can be designed for pulmonary delivery applications.

Hydrocortisone-loaded Lipid-Polymer Hybrid Nanoparticles for Macrophage Targeted Delivery in Chronic Obstructive Pulmonary Disease

The multifaceted illness known as a chronic obstructive pulmonary disease (COPD) is characterized by a decline in post-bronchodilator pulmonary function in all individuals and is linked to local and systemic inflammation, attracting alveolar macrophages (AM). The objective of this study was to use carubinose-linked hydrocortisone-hybrid nanoparticles (HC-HNPs) to increase the glycotargeting effectiveness to AM. The emulsification solvent evaporation method was used to generate the HC-HCNPs, and various analytical techniques were used to characterize them, including %entrapment efficiency, analytical characterization and histopathology examinations. Results revealed that HC is entrapped inside the hybrid preparations, which contain specific signatures of molecules that interact with ligands and are expressed all through the cell surface, as well as the amorphous nature of HC-HNPs. Field emission scanning electron microscopy (FESEM) revealed the surface structure and the particle size diameter which is enough to reach the AM through the nasal route. The high-performance liquid chromatography (HPLC) showed no interference from excipients in determining HC, indicating that the method is specific. The in-vivo findings showed that HC-HNPs demonstrated proof that very small and cost-effective nanoparticles can be developed to effectively target AM by effectively delivering HC-HNPs to the lungs.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of −13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity

BackgroundWith the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. MethodsLVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. ResultsData revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. ConclusionThese data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Microencapsulation of Acalypha indica Linn. Extracts Using Chitosan-Polycaprolactone Blends

Polymer encapsulation is commonly adopted in drug delivery systems to form encapsulation that can assist in delivering active compounds to the targeted area. Acalypha indica (AI) crude extract was obtained from AI plants through ultrasound-assisted extraction. It is naturally unstable in the external environment and, thus, needs to be encapsulated to protect against volatility. Herein, this study emphasized the development of the encapsulations of AI extracts using a chitosan-polycaprolactone (PCL) blend by emulsion-solvent evaporation and freeze-dried methods. Four parameters for Al encapsulation were studied by fixing one parameter at a time. The percentage of encapsulation efficiency (EE%) was recorded as a response for each parameter. The study proceeded with central composite design (CCD) as the response surface methodology (RSM) optimization tool to study the interactions between the factors. Central points were taken from the preliminary data obtained in one-parameter experiments. The validation was carried out with two data of the highest and lowest EE% suggested by CCD. The highest EE% recorded was 98.70%, and the lowest EE% was 87.80%. The results showed a difference between predicted and experimental values at a percentage lower than 7.5%. Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM), particle size analyzer, and zeta potential were used to analyze the properties of selected microencapsulated samples. Overall, the encapsulation of AI extracts was successful and has the potential to be used in drug delivery.

Functionalized hydroxypropyl‐β‐cyclodextrin derivative as a versatile nanovehicle for delivery of paclitaxel

AbstractTo improve the therapeutic efficiency of paclitaxel (PTX) and reduce its toxicity to normal tissues, a novel hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) derivative has been designed and developed. The polymer (bio‐HP‐β‐CD(NAC)‐PLA) is synthesized by modifying HP‐β‐CD with polylactic acid, cysteine, and biotin. Using bio‐HP‐β‐CD(NAC)‐PLA as the carrier, a PTX‐loaded nanoparticulate system is developed by a modified emulsion solvent evaporation method. The optimized drug‐loaded nanoparticles are obtained with a mean diameter of 162.4 nm and drug loading of 16.1%. In vitro drug release study exhibits that PTX is released in a redox‐dependent manner. Cellular uptake study suggests that the bio‐HP‐β‐CD(NAC)‐PLA nanoparticles can be specifically taken up by MCF‐7 cells via the biotin receptor‐mediated endocytosis. In vitro and in vivo anticancer efficacy evaluations demonstrate the superior antitumor activity and negligible toxicity of the PTX‐loaded nanoparticles. It can be concluded that the proposed polymer bio‐HP‐β‐CD(NAC)‐PLA offers a promising drug delivery system for targeted delivery and controlled release of PTX.

Ursolic acid loaded tri-block copolymer nanoparticles based on triphenylphosphine for mitochondria-targeted cancer therapy

A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay. In vitro cell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.

Optimisation of microencapsulation efficiency of propolis phenolic compounds by double emulsion method using response surface methodology

AbstractThe aim of this study was to optimise the microencapsulation efficiency of propolis phenolic compounds by double emulsion solvent evaporation technique (W1/O/W2). The solvent/sample ratio and the polymer and surfactant concentration parameters were optimised using response surface methodology (RSM) through Box–Behnken Design (BBD). For each parameter studied, total phenolic content encapsulation efficiency (TPCEE), free radical scavenging activity (DPPH), and ferric reducing antioxidant power (FRAP) were evaluated. The results showed that the optimal parameters were: 31.60 mg mL−1 for sample/solvent ratio, 606.28 mg mL−1 for poly(ε-caprolactone) (PCL) concentrations, and 2.05 g mL−1 for poly(vinyl alcohol) (PVA) concentration. The optimum values obtained were: 84.62% for encapsulation efficiency of phenolic content, 51.89% for DPPH, and 48,733 mg Trolox Equivalent/100 g dry weight for FRAP. The experimental checking of results revealed the validity of elaborated models and their suitability for the prediction of both responses. The developed mathematical models have expressed a high level of significance through RSM optimisation processes for phenolic antioxidants of propolis.

Formulation and Evaluation of Floating Microspheres

Gastro-retentive dosage forms have potential for use as controlled- release drug delivery systems. Gastro retentive floating drug delivery systems have a bulk density lower than that of gastric fluids and thus increase residence time of drug in stomach and provide controlled delivery of many drugs. The aim of the present study is formulation and characterization of floating microspheres using model drug. Floating microspheres were prepared by oil-in-water emulsion solvent evaporation technique using ethyl cellulose as release retarding polymers. The floating microspheres were evaluated for percentage yield (%), particle size, drug content, drug entrapment efficiency, in-vitro floating ability and in-vitro drug release studies. The surface morphology of prepared microspheres was characterized by scanning electron microscopy. The microspheres were found to be spherical in shape and porous in nature. Compatibility studies were performed by fourier transform infrared (FTIR) technique. The prepared microspheres showed prolonged drug release of 12 h and remain buoyant for more than 12 h. In-vitro release kinetics were studied in different release kinetics models like zero order, first order model. It was concluded that developed floating microspheres offers a suitable and practical approach for prolonged release of drug over an extended period of time and thus oral bioavailability, efficacy and patient compliance is improved

Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics.

Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment. The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits' eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC). The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug. PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization.

Development of Hydroxyapatite/Polycaprolactone Composite Biomaterials for Laser Powder Bed Fusion: Evaluation of Powder Characteristics, Mechanical Properties and Biocompatibility.

Hydroxyapatite/polycaprolactone (HA/PCL) composites have been extensively explored in laser powder bed fusion (L-PBF) for bone tissue engineering. However, conventional mechanical mixing methods for preparing composite powders often yield inhomogeneous compositions and suboptimal flowability. In this study, HA/PCL powders were prepared and optimized for L-PBF using the modified emulsion solvent evaporation method. The morphology, flowability and thermal and rheological properties of the powders were systematically investigated, along with the mechanical and biological properties of the fabricated specimens. The HA/PCL powders exhibited spherical morphologies with a homogeneous distribution of HA within the particles. The addition of small amounts of HA (5 wt% and 10 wt%) enhanced the processability and increased the maximum values of the elastic modulus and yield strength of the specimens from 129.8 MPa to 166.2 MPa and 20.2 MPa to 25.1 MPa, respectively, while also improving their biocompatibility. However, excessive addition resulted in compromised sinterability, thereby affecting both mechanical and biological properties.

Inhibiting Effect of Cationic Procyanidin Nanoparticles on Drug-Resistant Oral Squamous Cell Carcinoma Cell Lines

Background: Multidrug resistance (MDR) is one of the primary causes of tumor chemotherapy failure. Therefore, it is essential to uncover new drug treatment protocols. In the current study, employing chitosan (CS) and sodium tripolyphosphate (TPP) as carriers and cross-linking agents, the proanthocyanidins (PHL)/poly (lactic-co-glycolic acid) (PLGA) were encapsulated by emulsion solvent evaporation, through which the cationic CS-PLGA-PHL nanosystem was obtained. The effectiveness of CS-PLGAPHL on the invasion and migration of human oral squamous cell carcinoma cells was discussed, as were their potential mechanisms. Materials and Methods: A CS-PLGA-PHL nanosystem was constructed by emulsion-solvent evaporation. The size distribution, dispersion, and morphology were characterised by the laser particle size analyser and transmission electron microscope. Human oral squamous cell carcinoma drug-resistant cell lines SCC131/R and SCC-15/DDP were cultured in vitro. The two cell types were induced at different concentrations by CS-PLGA-PHL, after which a CCK⁃8 experiment was performed to determine the effect of CS-PLGA-PHL on the proliferation of the two cell lines. The 50% inhibitory concentration (IC50) of CSPLGA- PHL was calculated at different time points. The transwell chamber experiment was performed to identify the effects of CS-PLGA-PHL on the migration and invasion of OSCC cells. The expression levels of MMP-2 and MMP-9 were detected by Western blot and q-PCR. Results: CS-PLGA-PHL is well dispersed. The PDI appeared to be lowest when the mass ratio of chitosan to PLGA equaled 1:15. CS-PLGA-PHL exhibited a marked effect in inhibiting the proliferation of SCC- 131/R and SCC-15/DDP as well as the invasion and migration. CS-PLGA-PHL was able to downregulate the expression of MMP-2 and MMP-9 genes and proteins significantly in drug-resistant cell lines. Conclusion: CS-PLGA-PHL for oral squamous cell carcinoma has been successfully prepared to exert significant inhibition on the proliferation, invasion, and migration of OSCC cells. The mechanism involved was possibly related to the down-regulation of MMP-2 and MMP-9 expression by CS-PLGA-PHL.