Search Results (110)

The utilization of encapsulated biopharmaceuticals, including peptides and proteins, has grown substantially in recent years. In this study, the influence of aliphatic polyester physicochemical properties, specifically crystallinity and hydrophobicity, on the development of protein-loaded microparticles was investigated. A series of polyesters, namely amorphous PDLLA and semicrystalline PLLA, PCL, and PPDL, were synthesized via chemical and enzymatic ring-opening polymerization. Bovine serum albumin (BSA)-loaded microparticles were fabricated using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method. The size of microparticles obtained was determined by scanning electron microscopy and dynamic light scattering methods. The enzymatic degradation of the polymer microparticles was assessed through incubation in a lipase-containing buffer solution. BSA and α-chymotrypsin (ACHT) were used as model proteins for the preparation of encapsulated polymer microspheres and comparison of their characteristics and properties. Protein encapsulation efficacy, release rate, and enzyme activity retained after encapsulation were evaluated and compared for selected aliphatic polyesters. The release profiles were processed with the use of various mathematical models to reveal the possible mechanism(s) of protein release. Full article

Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article

Background/Objectives: Trimethoprim (TMP), a sulfonamide antibacterial synergist, is widely used in antimicrobial therapy owing to its broad-spectrum activity and clinical efficacy in treating respiratory, urinary tract, and gastrointestinal infections. However, its application is limited due to poor aqueous solubility, a short elimination half-life (t_1/2), and low bioavailability. In this study, we proposed TMP loaded by PEG-PLGA polymer nanoparticles (NPs) to increase its efficacy. Methods: We synthesized and thoroughly characterized PEG-PLGA NPs loaded with TMP using an oil-in-water (O/W) emulsion solvent evaporation method, denoted as PEG-PLGA/TMP NPs. Drug loading capacity (LC) and encapsulation efficiency (EE) were quantified by ultra-performance liquid chromatography (UPLC). Comprehensive investigations were conducted on the stability of PEG-PLGA/TMP NPs, in vitro drug release profiles, and in vivo pharmacokinetics. Results: The optimized PEG-PLGA/TMP NPs displayed a high LC of 34.0 ± 1.6%, a particle size of 245 ± 40 nm, a polydispersity index (PDI) of 0.103 ± 0.019, a zeta potential of −23.8 ± 1.2 mV, and an EE of 88.2 ± 4.3%. The NPs remained stable at 4 °C for 30 days and under acidic conditions. In vitro release showed sustained biphasic kinetics and enhanced cumulative release, 86% at pH 6.8, aligning with first-order models. Pharmacokinetics in rats revealed a 2.82-fold bioavailability increase, prolonged half-life 2.47 ± 0.19 h versus 0.72 ± 0.08 h for free TMP, and extended MRT 3.10 ± 0.11 h versus 1.27 ± 0.11 h. Conclusions: PEG-PLGA NPs enhanced the solubility and oral bioavailability of TMP via high drug loading, stability, and sustained-release kinetics, validated by robust in vitro-in vivo correlation, offering a promising alternative for clinical antimicrobial therapy. Full article

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention for Magnetic Fluid Hyperthermia (MFH)-based cancer therapy. However, achieving high heating efficiency under a biologically safe Alternating Magnetic Field (AMF) remains a challenge. This study investigates the synthesis and optimization of SPIONs encapsulated in TPGS-stabilized PLGA nanoparticles (TPS-NPs) using a modified single emulsion solvent evaporation (M-SESE) method. The aim was to achieve efficient magnetic heating under biologically safe AMF conditions while maintaining biocompatibility and colloidal stability, making these magnetic nanoplatforms suitable for MFH-based cancer treatment. TPS-NPs were characterized using various techniques, including Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID) magnetometry, to evaluate their hydrodynamic size (Dh), zeta potential (ζ), encapsulation efficiency, and superparamagnetic properties. Calorimetric MFH studies demonstrated superior heating efficiency, with Specific Absorption Rate (SAR) and Intrinsic Loss Power (ILP) values optimized at an AMF of 4.1 GAm⁻¹s⁻¹, remaining within Hergt’s biological safety limit (~5 GAm⁻¹s⁻¹). These findings suggest that SPION-encapsulated TPS-NPs exhibit enhanced heat induction, making them promising candidates for MFH-based cancer therapy. The study highlights their potential as multifunctional nanoplatforms for magnetic hyperthermia therapy, paving the way for clinical translation in oncology for advanced cancer treatment. Full article

Objectives: This study characterised and evaluated the stability, solubility, and in vitro drug release of OA- and AA-loaded SLNs. Methods: The OA- and AA-SLNs were formulated using the emulsion solvent evaporation method and characterised based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and transmission electron microscopy (TEM). Solubility studies were conducted in PBS (pH 1.2 and 6.8) and dH₂O using HPLC, while in vitro drug release was assessed in simulated intestinal fluid (SIF) (pH 6.8). Results: The optimised OA-SLNs (1:1 drug-to-lipid ratio) showed PS, PDI, ZP, and EE% values of 312.9 ± 3.617 nm, 0.157 ± 0.014, −17.0 ± 0.513 mV, and 86.54 ± 1.818%, respectively. The optimised AA-SLNs (1:2 drug-to-lipid: ratio) had a PS of 115.5 ± 0.458 nm, PDI of 0.255 ± 0.007, ZP of −11.9 ± 0.321 mV, and EE% of 76.22 ± 0.436%. The SLNs remained stable for 60 days at 4 °C and room temperature (p < 0.05). The solubility study revealed that free OA and AA showed no measurable values in the three solvents. However, OA-SLNs showed the highest solubility in H₂O (16-fold) followed by PBS at pH 6.8 (10-fold) and pH 1.2 (10-fold). AA-SLNs significantly improved the solubility in PBS at pH 6.8 (88-fold), compared to dH₂O (6-fold) and PBS at pH 1.2 (26-fold). In vitro drug release studies showed that OA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to the free drug. Similarly, AA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to free AA. Conclusions: These results demonstrate that SLNs enhance OA and AA solubility and drug release, suggesting a promising strategy for improving oral bioavailability and therapeutic efficacy. Full article

Background/Objectives: The limited permeability of the blood–brain barrier (BBB) to biotherapeutics is a major challenge in the treatment of brain tumors. The nose-to-brain (N2B) delivery approach, which bypasses the BBB, offers a promising alternative way to treat these tumors. The aim of this work was to develop PLGA nanoparticles for N2B delivery of biodrugs using trastuzumab (TZB) as a paradigm. Methods: An in vitro model was used to evaluate the ability of PLGA nanoparticles to enhance passage through the nasal epithelium. We also compared the passage of loaded TZB versus unencapsulated TZB across an in vitro BBB model simulating systemic administration of TZB. TZB-loaded PLGA nanoparticles (NP-TZBs) were prepared using a double emulsion method followed by solvent evaporation and characterized for various properties, including particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, and drug loading capacity and release kinetics. TZB functionality was assessed after release from NP or passage through an in vitro barrier model. The permeability of TZB and NP-TZBs through in vitro models of nasal epithelium and BBB was investigated. Results: NP-TZBs exhibited an average size of about 200 nm with a polydispersity index of less than 20%, neutral charge, and a loading efficiency of 67%. Transmission electron microscopy revealed spherical nanoparticles with a smooth surface. Importantly, the TZB released from the nanoparticles retained all of its physicochemical properties and functionality. We observed that the NP-TZB formulation results in at least a nine-fold increase in TZB permeability across the nasal epithelium 24 h post-exposure, depending on the exposure conditions, but shows no significant improvement across the BBB model. The TZB released in the basal compartment is fully functional and able to recognize HER2 expressed on the surface of breast tumor BT474 cells. Conclusions: Using compounds already validated for clinical use, we were able to develop a formulation that allowed efficient passage of TZB across an in vitro nasal epithelial model. In contrast, no passage was observed across the BBB, supporting the notion of the superiority of the nose–brain route over systemic injection for in vivo delivery of TZB to the central nervous system. Full article

Poor drug entrapment, burst release, and variable drug release profiles are the most critical challenges associated with biodegradable-polymer-based microspheres. In this study, biodegradable-polymer-based microspheres were used to entrap an antiplatelet drug, eptifibatide, using a single-emulsion solvent evaporation method. Critical challenges associated with biodegradable-polymer-based microspheres were addressed by incorporating different additives in the drug or polymer phase. Additives such as hydroxy propyl beta cyclodextrins (HPβCD), carboxy methyl cellulose sodium (Na CMC), and trehalose were added to the drug phase to evaluate their impact on the entrapment and stability of eptifibatide. The effect of the addition of additives such as polyvinyl alcohol (PVA), polyethylene glycol-400 (PEG-400), and methoxy polyethylene glycol phospholipid dimyristoyl phosphatidylethanolamine (mPEG-2000-DMPE, Na) to the polymer phase on the release profile of eptifibatide was evaluated. The inclusion of HPβCD resulted in good drug entrapment and helped control the initial unwanted burst release. Including Na CMC increased eptifibatide entrapment from 75% to 95%. Trehalose helped prevent the degradation of eptifibatide during lyophilization, and including PVA and PEG-400 reduced the lag phase and led to a controlled-release profile. Thus, including additives in the formulation can effectively improve the drug load and address issues associated with biodegradable-polymer-based microspheres. Full article

Background and objectives: The use of polymeric nanoparticles (NPs) in drug delivery systems offers the advantages of enhancing drug efficacy and minimizing side effects; Methods: In this study, L-threonine polyurethane (LTPU) NPs have been fabricated by water-in-oil-in-water emulsion and solvent evaporation using biodegradable and biocompatible LTPU. This polymer was pre-synthesized through the use of an amino acid-based chain extender, desaminotyrosyl L-threonine hexyl ester (DLTHE), where urethane bonds are formed by poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) triblock copolymer and 1,6-hexamethylene diisocyanate (HDI). LTPU is designed to be degraded by hydrolysis and enzymatic activity due to the presence of ester bonds and peptide bonds within the polymer backbone. LTPU NPs were fabricated by water-in-oil-in-water double emulsion solvent evaporation methods; Results: The polymerization of LTPU was confirmed by ¹H-NMR, ¹³C-NMR, and FT-IR spectroscopies. The molecular weights and polydispersity, determined with GPC, were 28,800 g/mol and 1.46, respectively. The morphology and size of NPs, characterized by DLS, FE-SEM, TEM, and confocal microscopy, showed smooth and spherical particles with diameters less than 200 nm; Conclusions: In addition, the drug loading, encapsulation efficiency, and drug release profiles, using UV-Vis spectroscopy, showed the highest encapsulation efficiency with 2.5% carboplatin and sustained release profile. Full article

The aim of this study was to develop a long-acting injectable formulation of risperidone using polylactic acid (PLA) or poly (lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer. Risperidone microspheres (RMs) were prepared by creating an O/W emulsion using dichloromethane (DCM) as a solvent and then employing the solvent evaporation method. The RMs were prepared with four different risperidone-to-PLGA ratios (1:1, 1:1.3, 1:2, and 1:3 (w/w)), and each ratio was subjected to the same manufacturing process. The physicochemical properties of the prepared RMs, such as their shape, particle size, drug loading ratio, encapsulation efficiency, and in vitro degradation profile, were evaluated. The particle size of the RMs ranged from 30 to 100 μm, with larger PLGA ratios resulting in larger RM sizes. The drug loading ratio was inversely proportional to the increase in the PLGA ratio in the RMs, and all the formulations showed improved release profiles compared to the reference drug, Risperdal Consta^®. The release data modeling results showed that the RM-3 formulation with a 1:1 (w/w) ratio of risperidone and PLGA exhibited a release pattern close to zero-order kinetics. The manufactured RMs were confirmed to have the potential to be used as a long-acting risperidone injection with sustained and stable release as well as an extended dosing interval. Full article

Background: Invasive aspergillosis (IA) is a deadly fungal lung infection. Antifungal resistance and treatment side effects are major concerns. Iron chelators are vital for IA management, but systemic use can cause side effects. We developed nanoparticles (NPs) to selectively deliver the iron chelator deferasirox (DFX) for IA treatment. Methods: DFX was encapsulated in poly(lactic-co-glycolic acid) (PLGA) NPs using a single emulsion solvent evaporation method. The NPs were characterized by light scattering and electron microscopy. DFX loading efficiency and release were assessed spectrophotometrically. Toxicity was evaluated using SRB, luciferase, and XTT assays. Therapeutic efficacy was tested in an IA mouse model, assessing fungal burden by qPCR and biodistribution via imaging. Results: DFX-NPs had a size of ~50 nm and a charge of ~−30 mV, with a loading efficiency of ~80%. Release kinetics showed DFX release via diffusion and bioerosion. The EC50 of DFX-NPs was significantly lower (p < 0.001) than the free drug, and they were significantly less toxic (p < 0.0001) in mammalian cell cultures. In vivo, NP treatment significantly reduced Af burden (p < 0.05). Conclusion: The designed DFX-NPs effectively target and kill Af with minimal toxicity to mammalian cells. The significant in vivo therapeutic efficacy suggests these NPs could be a safe and effective treatment for IA. Full article

Salmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, has been the most severe health concern for the Chilean salmon industry. The efforts to control P. salmonis infections have focused on using antibiotics and vaccines. However, infected salmonids exhibit limited responses to the treatments. Here, we developed a poly (D, L-lactide-glycolic acid) (PLGA)-nanosystem functionalized with Atlantic salmon IgM (PLGA-IgM) to specifically deliver florfenicol into infected cells. Polymeric nanoparticles (NPs) were prepared via the double emulsion solvent-evaporation method in the presence of florfenicol. Later, the PLGA-NPs were functionalized with Atlantic salmon IgM through carbodiimide chemistry. The nanosystem showed an average size of ~380–410 nm and a negative surface charge. Further, florfenicol encapsulation efficiency was close to 10%. We evaluated the internalization of the nanosystem and its impact on bacterial load in SHK-1 cells by using confocal microscopy and qPCR. The results suggest that stimulation with the nanosystem elicits a decrease in the bacterial load of P. salmonis when it infects Atlantic salmon macrophages. Overall, the IgM-functionalized PLGA-based nanosystem represents an alternative to the administration of antibiotics in salmon farming, complementing the delivery of antibiotics with the stimulation of the immune response of infected macrophages. Full article

Docetaxel (DTX) and betulinic acid (BA) co-encapsulated poly-lactic co-glycolic acid (PLGA) nanoparticles (NPs) were developed for enhanced lung cancer activity in vitro. Poly (lactic-co-glycolic acid) (PLGA) was used as an encapsulating polymer along with polyvinyl alcohol (PVA) as a stabilizing base to formulate NPs with the double-emulsion solvent evaporation method to study the size and potential, along with the surface morphology and in vitro release, of NPs. Cell culture studies like in vitro cellular uptake, apoptosis, and cell cycle arrest were performed in an in vitro cytotoxicity study to access the NP’s effect in the A549 human lung cancer cell line. The emulsification solvent evaporation technique produced smooth spherical nanoparticles of small sizes with a relatively narrow size distribution (147.2 ± 12.29 nm). On the A549 cell line, the formulation showed higher cytotoxicity (6.43 ± 0.11, 4.21 ± 0.32, and 1.17 ± 0.23 µmol for 24, 48, and 72 h, respectively) compared to the free drug due to an increase in vitro cellular uptake. Apoptosis and cell cycle analysis also confirmed the effectiveness of the prepared NPs. In vitro studies have proven the tumor-targeting potential of DTX-BA-NPs in A549 cell lines and could be future medication for lung cancer treatment. Full article

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr’s index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route. Full article

Poly(lactic-co-glycolic acid) (PLGA) hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and other versatile properties. This review comprehensively explores their synthesis, properties, sustained release mechanisms, and applications in drug delivery. The introduction underscores the significance of PLGA hydrogels in addressing challenges like short half-lives and systemic toxicity in conventional drug formulations. Synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, are described in detail and their role in tailoring hydrogel properties for specific applications is highlighted. Sustained release mechanisms—such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems—are analyzed alongside key kinetic models (zero-order, first-order, Higuchi, and Peppas models) for designing controlled drug delivery systems. Applications of PLGA hydrogels in drug delivery are discussed, highlighting their effectiveness in localized and sustained chemotherapy for cancer, as well as in the delivery of antibiotics and antimicrobials to combat infections. Challenges and future prospects in PLGA hydrogel research are discussed, with a focus on improving drug loading efficiency, improving release control mechanisms, and promoting clinical translation. In summary, PLGA hydrogels provide a promising platform for the sustained delivery of therapeutic agents and meet diverse biomedical requirements. Future advancements in materials science and biomedical engineering are anticipated to further optimize their efficacy and applicability in clinical settings. This review consolidates the current understanding and outlines future research directions for PLGA hydrogels, emphasizing their potential to revolutionize therapeutic delivery and improve patient outcomes. Full article

Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS’s limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (−37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG_2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy. Full article