Microparticle Formulations Research Articles

Diffusion and Exchange Kinetics of Microparticle Formulations by Spatial Fourier Transform Fluorescence Recovery after Photobleaching with Patterned Illumination.

The mechanism of active pharmaceutical ingredient (API) mobility during release in microparticle formulation was investigated using periodically structured illumination combined with spatial Fourier transform fluorescence recovery after photobleaching (FT-FRAP). FT-FRAP applies structured photobleaching across a given field of view, allowing for the monitoring of molecular mobility through the analysis of recovery patterns in the FT domain. Encoding molecular mobility in the FT domain offers several advantages, including improved signal-to-noise ratio, simplified mathematical calculations, reduced sampling requirements, compatibility with multiphoton microscopy for imaging API molecules within the formulations, and the ability to distinguish between exchange and diffusion processes. To prepare microparticles for FT-FRAP analysis, a homogeneous mixture of dipyridamole and pH-independent methyl methacrylate polymer (Eudragit RS and RL) was processed using laminar jet breakup induced by vibration in a frequency-driven encapsulator. The encapsulated microparticles were characterized based on particle size distribution, encapsulation efficiency, batch size, and morphology. Utilizing FT-FRAP, the internal diffusion and exchange molecular mobility within RL and RS microparticles were discriminated and quantified. Theoretical modeling of exchange- and diffusion-controlled release revealed that both RL and RS microparticles exhibited similar exchange decay rates, but RL displayed a significantly higher diffusion coefficient. This difference in diffusion within RL and RS microparticles was correlated with their macroscopic dissolution performance.

Spray-dried cyclophosphamide-loaded polyhydroxyalkanoate microparticles: design and characterization

Background and purpose: Cyclophosphamide (CP) is a widely used antitumor and immunosuppressive drug, but it is highly cytotoxic and has carcinogenic and teratogenic potential. To reduce adverse effects of CP therapy and the frequency of its administration, the microencapsulation of CP into biodegradable polymeric matrices can be performed. However, according to the literature, only a few polymers were found suitable to encapsulate CP and achieve its’ sustained release. Experimental approach: In this research, spray-dried cyclophosphamide-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were prepared and characterized in terms of their average hydrodynamic diameter, polydispersity index, surface morphology, zeta potential, encapsulation efficiency, drug loading, thermal properties and cytotoxicity against 3T3 cells. Key results: The obtained CP-loaded microparticles had a regular spherical shape, uniform size distribution with an average diameter of 4.21±0.04 μm and zeta potential of -34.2±0.2 mV. The encap­sulation of cyclophosphamide into the PHBV matrix led to a decrease in melting and degradation tempe­ratures and an increase in diameter, glass transition and cold crystallization temperatures compared to blank microparticles. Moreover, microencapsulation of cyclophosphamide lowered its cytotoxicity compared to the pure drug: the number of dead cells in the culture decreased by 28 %, while their metabolic activity increased by 20 %. The cumulative in vitro drug release studies showed a gradual release of CP up to 18 days, so the obtained microparticle formulation can be used as a sustained-release cyclophosphamide delivery system. Conclusion: In this research, a novel cyclophosphamide-loaded platform based on PHBV micro­particles was established and characterized. Overall, this study offers promising prospects for cancer therapy in the future.

Formulation and Evaluation of Glipizide-loaded Mucoadhesive Microparticle Using Salvia hispanica Seeds Mucilage as Co-polymer

Aims: Chia seed (Salvia hispanica L.) gum is a mucoadhesive, biodegradable polymer with sustained release properties. Objective: The objective of this study was to compare different formulations of glipizide-loaded microparticles using chia seed mucilage and sodium alginate, focusing on sustained release and mucoadhesive properties. Background: The present study aimed to comparatively evaluate various eco-friendly formulations of glipizide-loaded microparticles prepared using chia seed mucilage and sodium alginate. Materials and Methods: Gum was extracted from chia seeds and lyophilized, and preformulation studies were performed according to established protocols. Microparticles were formulated using the ionic gelation method, with sodium alginate as a copolymer and zinc chloride as a cross-linking agent. The prepared microparticles were evaluated using scanning electron microscopy (SEM) for size and particle aggregation, and Fourier Transform infrared spectroscopy (FTIR) for drug-polymer interaction, entrapment efficiency, swelling index, and in vitro drug release. Results: The % yield of chia seed mucilage was 27.35%. The pH of the mucilaginous suspension was 4.67 ± 0.50. The moisture content value was 14.56 % ± 0.50. The values of Carr's index and Hausner's ratio were 22.58 ± 1.89 and 1.38 ± 0.05, respectively. FTIR spectra showed no interaction between pure glipizide and chia seed mucilage, confirming no possible change in glipizide's pharmacology. SEM studies have confirmed the shape of the microparticles to be spherical, with average sizes ranging from 1235.18 ± 8.7 to 1423.25 ± 9.5 µm, and the drug entrapment efficiency ranged from 64.25 ± 2.52 to 81.82 ± 7.56%. The release of glipizide from the microparticles was sustained, and the Higuchi and Korsmeyer-Peppas models were found to be the best-fit kinetic models. Conclusion: The promising copolymer blend of chia seed mucilage and sodium alginate was used for the development of sustained-release dosage forms. A copolymer blend with a ratio of 1:1 produced glipizide-loaded microparticles with sustained release profiles and good mucoadhesive ability, along with a high percentage of drug entrapment efficiency.

An aerosol nanocomposite microparticle formulation using rifampicin-cyclodextrin inclusion complexes for the treatment of pulmonary diseases

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world’s population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB.

Pharmacokinetics of nano- and microcrystal formulations of low solubility compounds after intramuscular injection to mice.

The aim of this study was to investigate the pharmacokinetics (PK) of poorly soluble compounds when administered intramuscularly (i.m.) as crystalline particles of different sizes. Three uncharged compounds (griseofulvin, AZ'72, and AZ'07) with varying aqueous solubility were dosed to mice at 10 and 50mg/kg as nano- and microparticle formulations. The PK of the compounds was evaluated. The smaller particles of the drugs resulted in higher maximum plasma concentration (Cmax) and area under the plasma concentration-time profile (AUC) at 50mg/kg. There was a dose-proportional increase in AUC but less than dose dose-proportional increase in Cmax. The evaluation at 10mg/kg was more complex as increased exposure for nanoparticles was only observed for griseofulvin which has the highest solubility. In addition, there was an increase in half-life with an increase in dose. This study highlights that general expectations based on in vitro dissolution (i.e. that smaller particles dissolve faster than larger particles when surrounded by liquid) do not always translate to in vivo and demonstrates the importance of understanding the physicochemical properties of the drug, the characteristics of the formulations and the microphysiology at the delivery site.

Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease.

To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. 4 healthy horses without evidence of forelimb lameness. A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points. Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point. Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.

Microencapsulation for the delivery of terazosin hydrochloride: design, development, and characterization

The aim of the work. Terazosin HCL, which is a selective alpha-1 antagonist, has been recommended for the treatment of benign prostatic hyperplasia-related medical conditions, including hypertension and urinary tract disorders. The purpose of this research was to create microparticles that would have a prolonged release of terazosin hydrochloride (TZ). However, TZ is a medicine that is readily soluble and has a high capability of dissolving in water. Materials and methods. A validated HPLC method was established to assess TZ. The TZ microparticles were produced using the process of melt dispersion by utilising cetyl palmitate (CP), myristic acid (MA), Glycerol monostearate 4055 (type II) or Kolliwax® GMS II (GMS), polyethylene glycol 400 (PEG 400) as a plasticizer, and tween 80 as a stabilizing agent. Different formulations of TZ microparticles were evaluated with regard to particle size, zeta potential, and release, and morphological scanning was performed. Results. A zeta potential that falls between -22.9 and -29.4 mV is possessed by TZ microparticles. Furthermore, the size of TZ microparticles falls between 2.11 and 5.60 µm, and the polydispersity index (PDI) was between 0.24 to 0.41. In addition, the formula (F4) that included CP, GMS, PEG 400, and Tween 80 in the proportions of 0.8:0.2:1:0.5 had the highest zeta potential (ZP) and dissolved more than 85 % of TZ after 8 hours. Therefore, F4 was chosen for the purpose of conducting morphological research. Conclusion. Employing the use of CP, GMS, PEG 400, and Tween 80 in a ratio of 0.8:0.2:1:0.5 could result in the generation of microparticles of TZ that are the most acceptable

Enhancing antioxidant properties of lime juice powder through polyelectrolyte microparticles of chitosan-alginate: Formulation, characterization and stability study.

Lime (Citrus aurantifolia) juice was reported to contain ascorbic acid (AA) and flavonoids, which has bioactivity as antioxidants. To develop an antioxidant product, improving its stability is necessary due to the perishable characteristics of compounds in lime. Therefore, the formulation of polyelectrolyte microparticles using chitosan and alginate was conducted to overcome the weaknesses. This study aims to evaluate the effect of various chitosan, alginate, and lime juice powder (LJP) concentrations on the physical characteristics and antioxidant activity of LJP encapsulated in chitosan-alginate microparticles (CALM). Microparticles with various concentrations of chitosan and alginate were prepared by ionic gelation method using CaCl2 as a crosslinker. The microparticles were evaluated for its physical properties and its antioxidant activity using 2-2-diphenyl-1-picrylhydrazyl reagent. A one-way ANOVA test and Tukey's honest significant difference post hoc were used to determine the effect of LJP amount on the antioxidant activity. The highest AA content in CALM was 0.14 mg/100 mg, with a % encapsulation efficiency of 18.38% ± 0.02%. Antioxidant activity tests revealed that LJP possessed the strong antioxidant activity with an IC50 value of 32.59 μg/mL, whereas IC50 values of the microparticles ranged from 24.79 ± 0.03 μg/mL to 39.96 ± 0.07 μg/mL. During storage, the IC50 of LJP decreased from 32.59 ± 0.13 μg/mL to 65.53 ± 0.03 μg/mL, whereas the IC50 of microparticles remained stable. This study concluded that the chitosan-alginate polyelectrolyte microparticle formulation can improve and protect LJP's antioxidant activity.

Formulation and Evaluation of Polysaccharide Microparticles for the Controlled Release of Propranolol Hydrochloride.

Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug's short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.

High-yield fabrication of monodisperse multilayer nanofibrous microparticles for advanced oral drug delivery applications

Recent advances in the use of nano- and microparticles in drug delivery, cell therapy, and tissue engineering have led to increasing attention towards nanostructured microparticulate formulations for maximum benefit from both nano- and micron sized features. Scalable manufacturing of monodisperse nanostructured microparticles with tunable size, shape, content, and release rate remains a big challenge. Current technology, mainly comprises complex multi-step chemical procedures with limited control over these aspects. Here, we demonstrate a novel technique for high-yield fabrication of monodisperse monolayer and multilayer nanofibrous microparticles (MoNami and MuNaMi respectively). The fabrication procedure includes sequential electrospinning followed by micro-cutting at room temperature and transfer of particles for collection. The big advantage of the introduced technique is the potential to apply several polymer-drug combinations forming multilayer microparticles enjoying extracellular matrix (ECM)-mimicking architecture with tunable release profile. We demonstrate the fabrication and study the factors affecting the final three-dimensional structure. A model drug is encapsulated into a three-layer sheet (PLGA-pullulan-PLGA), and we demonstrate how the release profile changes from burst to sustain by simply cutting particles out of the electrospun sheet. We believe our fabrication method offers a unique and facile platform for realizing advanced microparticles for oral drug delivery applications.

Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended-release microparticle formulation: A phase 1, dose-ascending study in male volunteers.

A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.

Ecofriendly cascade extraction of antioxidants from Origanum vulgare: Morphological and rheological behavior of microparticles formulations

Bioactive compounds from Origanum vulgare have been extracted to enriched foods. This has contributed to consumer acceptance. These extracts have been obtained using a sequential extraction process to recover the maximum amount of the bioactive compounds for the formulation of microparticles. Extracts obtained from both extraction technologies (ultrasound and pressurized hot water extraction) were analyzed. When the ultrasound technology was used, total phenolic content and protein content were highest (29 % and 4.7 %, respectively). The second extraction showed lower values around 72 % for TEAC value, 14 % phenolic content and 5.4 % protein content (g/100 extract). The IC50 for the ultrasound extract is 0.27 g/L and the lower value for the sequential treatment is 0.49 g/L. The polymeric microparticles were formulated with the ultrasound extract at different percentages of mannitol (2 % and 5 %). It was observed that microparticles (5 % mannitol) had a smaller particle size distribution (∼12 µm) and flow curves exhibiting shear-thinning behavior, which were successfully fitted with the power law model.

Immune Potentiation of PLGA Controlled-Release Vaccines for Improved Immunological Outcomes.

With the emergence of SARS-CoV-2 and the continued emergence of new infectious diseases, there is a need to improve and expand current vaccine technology. Controlled-release subunit vaccines provide several benefits over current vaccines on the market, including the use of less antigen and fewer boost doses. Previously, our group reported molecules that alter NF-κB signaling improved the vaccine's performance and improved adjuvant-related tolerability. In this report, we test how these immune potentiators will influence responses when included as part of a controlled-release poly(lactic-co-glycolic) vaccine formulation. Murine in vivo studies revealed that SN50 and honokiol improved antibody levels at early vaccine time points. Microparticles with SN50 produced strong antibody levels over a longer period compared to microparticles without SN50. The same particles also increased T-cell activity. All of the immune potentiators tested further promoted Th2 humoral responses already exhibited by the control CpG OVA microparticle formulation. Overall, under controlled-release conditions, immune potentiators enhance the existing effects of controlled-release formulations, making it a potentially beneficial additive for controlled-release vaccine formulations.

Development of Aerosol Dry Powder Chemotherapeutic-Loaded Microparticles for the Treatment of Lung Cancer

Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in the highest mortality rates among both men and women with respect to all other types of cancer. Difficulties in treating lung cancer arise from late-stage diagnoses and tumor heterogeneity and current treatment involves a combination of chemotherapeutics, surgery, and radiation. Chemotherapeutics administered systemically can lead to undesirable side effects and severe off-site toxicity. For example, chronic administration of the chemotherapeutic doxorubicin (DOX) leads to cardiotoxicity, thereby limiting its long-term use. Systemic administration of the highly lipophilic molecule paclitaxel (PTX) is hindered by its water solubility, necessitating the use of solubilizing agents, which can induce side effects. Thus, in this investigation, formulations consisting of spray-dried microparticles (MP) containing DOX and PTX were produced to be administered as dry powder aerosols directly to the lungs. Acetalated dextran (Ac-Dex) was used as the polymer in these formulations, as it is a biocompatible and biodegradable polymer that exhibits pH-responsive degradation. Solid-state characterization revealed that DOX and PTX remained in solubility favoring amorphous states in the MP formulations and that both drugs remained thermally stable throughout the spray drying process. In vitro release studies demonstrated the pH sensitivity of the formulations due to the use of Ac-Dex, as well as the release of both therapeutics over the course of at least 48 h. In vitro aerosol dispersion studies demonstrated that both formulations exhibited suitable aerosol dispersion properties for deep lung delivery.Graphical

Potential of DPD ((S)-4,5-dihydroxy-2,3-pentanedione) Analogs in Microparticulate Formulation as Vaccine Adjuvants.

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is involved in bacterial communication. DPD is the precursor of signal molecule autoinducer-2 (AI-2) and has high potential to be used as a vaccine adjuvant. Vaccine adjuvants are compounds that enhance the stability and immunogenicity of vaccine antigens, modulate efficacy, and increase the immune response to a particular antigen. Previously, the microparticulate form of (S)-DPD was found to have an adjuvant effect with the gonorrhea vaccine. In this study, we evaluated the immunogenicity and adjuvanticity of several synthetic analogs of the (S)-DPD molecule, including ent-DPD((R)-4,5-dihydroxy-2,3-pentanedione), n-butyl-DPD ((S)-1,2-dihydroxy-3,4-octanedione), isobutyl-DPD ((S)-1,2-dihydroxy-6-methyl-3,4-heptanedione), n-hexyl-DPD ((S)-1,2-dihydroxy-3,4-decanedione), and phenyl-DPD ((S)-3,4-dihydroxy-1-phenyl-1,2-butanedione), in microparticulate formulations. The microparticulate formulations of all analogs of (S)-DPD were found to be noncytotoxic toward dendritic cells. Among these analogs, ent-DPD, n-butyl-DPD, and isobutyl-DPD were found to be immunogenic toward antigens and showed adjuvant efficacy with microparticulate gonorrhea vaccines. It was observed that n-hexyl-DPD and phenyl-DPD did not show any adjuvant effect. This study shows that synthetic analogs of (S)-DPD molecules are capable of eliciting adjuvant effects with vaccines. A future in vivo evaluation will further confirm that these analogs are promising vaccine adjuvants.

Development of Ethylcellulose Microparticles for Taste Masking of Fexofenadine.

For taste masking of fexofenadine hydrochloride (FXD), ethylcellulose (EC) microparticles with FXD were developed. The amounts of EC, Tween 80, and polyvinyl alcohol (PVA) in the composition had little effect on initial drug release properties. Based on the results of the drug recovery and the drug release properties, FXD(EC200) was the optimal FXD microparticle formulation. From the results of Fourier transform infrared spectroscopy spectra and X-ray diffraction patterns of FXD(EC200), FXD amorphization in the microparticles and interaction between FXD and other components were suggested, and the formation of a solid dispersion of FXD was suggested. Because the possibility of the complex of PVA and FXD on the particle surface was suggested, sodium lauryl sulfate (SLS) was added to the composition. The initial drug release from FXD microparticles with SLS was further suppressed compared with FXD(EC200). From these results, FXD microparticles with SLS can be prepared as a controlled-release formulation and are expected to be useful for masking the bitter tasting particulates.

Comparison of emulsion and spray methods for fabrication of rapamycin-loaded acetalated dextran microparticles.

Rapamycin (rapa), an immunosuppressive medication, has demonstrated considerable effectiveness in reducing organ transplant rejection and treating select autoimmune diseases. However, the standard oral administration of rapa results in poor bioavailability, broad biodistribution, and harmful off-target effects, necessitating improved drug delivery formulations. Polymeric microparticles (MPs) are one such solution and have demonstrated promise in pre-clinical studies to improve the therapeutic efficacy of rapa. Nevertheless, MP formulations are highly diverse, and fabrication method selection is a critical consideration in formulation design. Herein, we compared common fabrication processes for the development of rapa-loaded MPs. Using the biopolymer acetalated dextran (Ace-DEX), rapa-loaded MPs were fabricated by both emulsion (homogenization and sonication) and spray (electrospray and spray drying) methods, and resultant MPs were characterized for size, morphology, surface charge, and drug release kinetics. MPs were then screened in LPS-stimulated macrophages to gauge immunosuppressive efficacy relative to soluble drug. We determined that homogenized MPs possessed the most optimal combination of sizing, tunable drug release kinetics, and immunosuppressive efficacy, and we subsequently demonstrated that these characteristics were maintained across a range of potential rapa loadings. Further, we performed in vivo trafficking studies to evaluate depot kinetics and cellular uptake at the injection site after subcutaneous injection of homogenized MPs. We observed preferential MP uptake by dendritic cells at the depot, highlighting the potential for MPs to direct more targeted drug delivery. Our results emphasize the significance of fabrication method in modulating the efficacy of MP systems and inform improved formulation design for the delivery of rapa.

Formulation and evaluation of Psidium guajava leaf extract microparticles

Formulation and evaluation of Psidium guajava leaf extract microparticles

Engineering hemin-loaded hyaluronan needle-like microparticles with photoprotective properties against UV-induced tissue damage.

This study aimed to develop hyaluronan (HA)-based hydrogel microparticles (MPs) loaded with hemin to address the limitations of traditional macroscale hydrogels. The objective is to design MPs such that they can modulate their physicochemical properties. Given the widespread use of ultraviolet C (UVC) light in various industries and the need for protective measures against accidental exposure, this study evaluated the potential of hemin-loaded MPs to protect human dermal fibroblasts from oxidative stress and cell death caused by UVC exposure. Multiple MP formulations were developed and analysed for size, surface charge, swelling behaviour, degradation rate, and radical scavenging capabilities, both with and without hemin loading. The most promising formulations were tested against UVC-exposed cells to assess cell viability, intracellular nitric oxide (˙NO) and reactive oxygen species levels, and protein carbonylation. The fabricated particles were in the form of microneedles, and the degree of their crosslinking and the role of hemin in the chemical crosslinking reaction were found to influence the surface charge and hydrodynamic diameter of the MPs. Increased crosslinking resulted in reduced swelling, slower degradation, and decreased hemin release rate. MPs with a higher degree of swelling were capable of releasing hemin into the culture medium, leading to enhanced bilirubin generation in dermal fibroblasts following cellular uptake. Pre-treatment with these MPs protected the cells from UVC-induced cell death, nitrosative stress, and protein carbonylation. These findings highlight the potential of the studied MPs to release hemin and to minimise the harmful effects of UVC on dermal fibroblasts.

Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration.

The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% (v/v%), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin.