Celecoxib was used as a model compound in fasted state simulated colonic fluid (FaSSCoF) to investigate equilibrium drug solubility (Seq), protein binding using rapid equilibrium dialysis (RED), flux and permeability (Papp) across porcine colonic mucus (PCM), and in vivo colonic absorption using a rat intracolonic instillation model. The primary focus was on the role of bovine serum albumin (BSA) as a solubilizing and binding constituent, while bile salts (sodium taurodeoxycholate, TDC) with lecithin and poloxamer 407 were included as comparative systems to evaluate how differences in solubilizer type influence celecoxib permeability and absorption. BSA demonstrated a pronounced solubilizing effect on celecoxib with a 1:1 molar binding ratio, increasing the apparent Seq from 5.1 µg/mL to 92 µg/mL in FaSSCoF containing 15 mg/mL BSA. Under these conditions, diffusion across PCM increased approximately seven-fold compared with FaSSCoF without BSA, accompanied by a four-fold increase in colonic absorption in vivo. In contrast, when celecoxib concentration was maintained constant and BSA was subsequently added to FaSSCoF, diffusion across PCM decreased up to ten-fold at BSA concentrations of 1.5 mg/mL, accompanied by an approximately 30% decrease in colonic absorption in vivo. This behavior is consistent with an increased BSA-bound fraction and a reduced free drug concentration available for transport. The addition of TDC with lecithin or poloxamer 407 similarly increased celecoxib diffusion across PCM and colonic absorption when celecoxib was dissolved at Seq in FaSSCoF, although no statistically significant differences were observed between the solubilizing systems. Overall, these findings demonstrate that solubilizing constituents in colonic fluids can substantially increase drug solubility, mucus permeation, and colonic absorption, highlighting the importance of accounting for protein–drug interactions when evaluating drug behavior in the colon.

This study aimed to investigate the cosmeceutical effects of cricket extracts and assess their delivery through a nanoemulsion system. Different species of crickets (Gryllus bimaculatus, Teleogryllus mitratus, and Acheta domesticus) were freeze-dried, defatted, and extracted using aqueous, enzyme-assisted, and protein isolation methods. Extracts were evaluated for total protein content, amino acid composition, anti-tyrosinase, and anti-hyaluronidase activities. The most bioactive extract was incorporated into an oil-in-water nanoemulsion, which was characterized for droplet size, polydispersity index (PDI), zeta potential, morphology, entrapment efficiency (EE), release profile, in vitro permeation and retention. The Subtilisin A-assisted extract of T. mitratus (TMS) contained the highest protein content (76.0 ± 1.1% w/w) and potent bioactivity, with tyrosinase IC50 values of 65.4 ± 6.9 μg/mL (L-tyrosine) and 395.9 ± 77.2 μg/mL (L-DOPA), and an anti-hyaluronidase IC50 of 12.5 ± 3.5 μg/mL. Nanoemulsion incorporation achieved 46.36 ± 1.69% EE and 0.20 ± 0.01% loading capacity, with nanoscale droplet sizes (288.3 ± 11.3 nm) and high stability (PDI < 0.3; zeta potential < -30 mV). Therefore, the TMS-loaded nanoemulsion provided multifunctional cosmeceutical benefits.

This study aimed to enhance the topical delivery of Teleogryllus mitratus protein hydrolysate (TM) by forming hydrophobic ion-pair (HIP) complexes with dioctyl sodium sulfosuccinate (DS) and incorporating them into lipid-based nanocarriers. TM was extracted via an enzyme-assisted method and complexed with DS to form TM-HIP. Chitosan nanoparticles (CNP), nanoemulsions (NE), and nanostructured lipid carriers (NLC) containing TM or TM-DS were prepared and characterized for particle size, polydispersity, zeta potential, encapsulation efficiency (EE), loading capacity (LC), and in vitro release. Membrane retention was assessed using Strat-M® membranes in Franz diffusion cells. The results showed that TM successfully formed a HIP complex with DS, resulting in an increased diffusion coefficient. All nanocarriers exhibited nanoscale particle sizes (∼70-300 nm), narrow distributions (PDI 0.17-0.26), and stable zeta potentials (-30 to -37 mV). Lipid-based nanocarriers containing TM-DS demonstrated the highest EE (TM-DS-NE: 76.8 ± 0.5%; TM-DS-NLC: 81.9 ± 2.4%) and sustained release, while CNP showed lower EE (17.6 ± 3.1%). Membrane retention studies revealed that TM-DS-NE (49.9 ± 0.7 μg/cm2) and TM-DS-NLC (50.1 ± 3.1 μg/cm2) achieved significantly higher protein deposition than TM-CNP (1.6 ± 0.8 μg/cm2), TM-NE (6.4 ± 1.2 μg/cm2), TM-NLC (9.2 ± 1.7 μg/cm2), or TM solution (1.2 ± 0.7 μg/cm2), with NLC identified as the most effective carrier. Therefore, it can be concluded that hydrophobic ion-pairing of TM with DS enhanced compatibility with lipid-based nanocarriers, resulting in improved encapsulation and membrane retention. The combination of protein lipophilicity, carrier composition, and nanoscale size effectively promoted delivery into the Strat-M® membranes. Further clinical studies are recommended to validate efficacy and safety under physiologically relevant conditions.

Salmon calcitonin (sCT) is a peptide with poor enzymatic stability and permeability, limiting its oral delivery. This study investigated how hydrophobic ion pair (HIP) type and self-nanoemulsifying drug delivery systems (SNEDDS) composition influence the oral delivery of sCT, and whether in vitro findings correlate with in vivo outcomes. HIPs were prepared with sodium caprate (C10) or sodium docusate (DOC) and incorporated into two SNEDDS differing in a single excipient: F1 contained 10% lysophosphatidylcholine (LPC), a natural permeation enhancer, while F2 replaced LPC with propylene glycol. In vitro, sCT:C10 provided no protection against trypsin, whereas sCT:DOC did (p < 0.05 vs native sCT). Incorporating HIPs into SNEDDS enhanced sCT proteolytic stability against trypsin relative to native sCT, but the extent was formulation-dependent, with F1 showing lower protection than F2 for the same HIP. Permeability in Caco-2 cells was mainly driven by SNEDDS, with F1 consistently showing lower FD4 transport than F2, indicating no additional benefit from LPC. In vivo, sCT:C10 showed no significant difference in relative pharmacological activity (PArel) over native sCT, whereas sCT:DOC significantly increased activity. HIP-loaded SNEDDS enhanced sCT activity compared with native sCT, yet F1 did not improve activity beyond F2. Among all groups, sCT:DOC in F2 achieved the highest PArel (8.8 ± 0.8%), indicating more favourable conditions for sCT oral delivery. In addition, in vitro trends correlated well with in vivo outcomes. Overall, HIP type and SNEDDS composition significantly influenced oral sCT delivery, highlighting the need to co-optimize these parameters to achieve effective oral peptide delivery.

Rosemary (Rosmarinus officinalis L.) is a rich source of rosmarinic acid (RA), a bioactive compound with strong in vitro evidence supporting its cosmeceutical potential. However, RA has moderate polarity (log P = 1.7), which limits its skin penetration. This study aimed to identify formulations and application methods capable of delivering RA into the skin at cosmetically relevant concentrations while minimizing systemic absorption. Rosemary extract containing RA (76% w/w) was characterized for solubility and incorporated into various liquid formulations, including an aqueous solution, propylene glycol solution, an oil-in-water (o/w) nanoemulsion, and a water-in-oil (w/o) nanoemulsion. Dissolving microneedle (DMN) patches containing the liquid formulations were also fabricated and evaluated. Three delivery strategies were compared: (i) liquid formulations applied to intact skin, (ii) liquid formulations applied after pretreatment of the skin with a metal microneedle (MMN) device, and (iii) DMN patches applied to intact skin. Among these, DMN patches loaded with rosemary extract (DMN-F1) achieved significantly lower transdermal permeation (0.99 ± 0.16%) than when an aqueous RA solution was applied to the skin after MMN pretreatment (56 ± 13%), but a higher skin retention (1.51 ± 0.05%) compared with rosemary extract aqueous solution applied to intact skin (0.24 ± 0.05%). Overall, the application of RA-loaded DMN patch to the skin proved the most effective approach, enabling efficient dermal delivery of RA while reducing transdermal delivery and, hence, potentially also systemic absorption. These findings highlight DMNs as a promising delivery platform for rosemary extract in anti-aging cosmetic applications.

Despite their favorable biopharmaceutical properties, exosomes face standardization challenges in isolation and characterization, hindering the development of EV products suitable for clinical applications. The MRC-5 cell line poses a cellular model approved by regulatory affairs for drug development, facilitating the clinical translation of MRC-5 cell-derived nanotherapeutics. This study aims to: (a) identify the optimal methodology for isolating intact MRC-5 cell-derived exosomes with high purity and integrity suitable for drug delivery applications, (b) elucidate the global miRNA and proteomic profile of the isolated exosomes using high-throughput methodologies and bioinformatics, (c) investigate the exosome uptake capacity towards the "autologous" normal MRC-5, and "heterologous" malignant human lung adenocarcinoma A549 and tongue squamous HSC-3 cells, (d) evaluate the pharmacological profile of doxorubicin (DOX)- and curcumin (CUR)- loaded exosomes towards the normal and tumorigenic cells in vitro. The proposed isolation protocol combining ultrafiltration with membrane-based affinity binding, yielded non-aggregated exosomes with superior physicochemical properties. The miRNA profiling data revealed the enrichment of several tumor-suppressive miRNAs mainly involved in gene regulation pathways, whilst the proteomic profiling highlighted the role of exosomal protein in extracellular matrix remodeling. The drug delivery profiling indicated an "intrinsic" tropism of the exosomes towards the malignant A549 and HSC-3 cells. Exosomal CUR and exosomal DOX inhibited tumor cell proliferation more efficiently than free drugs, with synergistic effects upon co-administration. This study provides a comprehensive morphological, physicochemical and molecular characterization of MRC-5 cell-derived exosomes and validates the "intrinsic" tropism of CUR- and DOX- loaded exosomes towards tumorigenic cells, paving the way towards their further exploitation as drug delivery nanocarriers.

Acheta domesticus protein hydrolysate (PH) is a natural anti-skin aging compound, but its effectiveness is hindered by poor skin penetration due to its hydrophilicity and high molecular weight. This study aimed to compare the enhancement of PH skin delivery by increasing lipophilicity with nanostructured lipid carriers (NLCs) and bypassing the skin barrier using physical techniques, including Derma Stamp and dissolving microneedles (MNs). Fluorescein isothiocyanate (FITC)-tagged PH was prepared to track the transdermal transport, and complexed with dioctyl sodium sulfosuccinate (DSS) to be encapsulated into NLCs, prepared using a melt emulsification method. Skin delivery was evaluated in terms of skin permeation and skin retention using Franz diffusion cells. The FITC-PH loaded NLCs had a particle size of 238.9 f 0.8 nm, a polydispersity index of 0.3 f 0.0, a zeta potential of -23.6 f 1.0 mV, and an encapsulation efficiency of 65.1 f 2.1 %. The MNs, prepared with polyvinylpyrrolidone K30 and polyvinyl alcohol (38:15 wt ratio), had uniform sharp needles and a high FITC-PH loading capacity of 97.2 f 1.9 %. PH permeation was most effectively enhanced through physical barrier bypassing, particularly with the Derma Stamp, followed by MNs and finally due to incorporation into NLCs. Notably, when utilizing the Derma Stamp, converting the aqueous solution of PH into an NLC formulation added positive benefits by significantly improving skin retention. In conclusion, it was suggested that while physical enhancement methods are crucial for permeation of the PH, optimizing formulation characteristics, such as incorporation into NLCs, further increased the overall effectiveness of skin delivery.

Double emulsions are potential oral delivery systems for the simultaneous administration of hydrophilic drugs and hydrophobic permeation enhancers to enable effective intestinal absorption of macromolecular drugs. Emulsions stabilized by solid particles, i.e., Pickering stabilizers, have shown potential to form gastric-stable emulsions that can protect their cargo from release under gastric conditions. Here, we use acylated cellulose nanocrystals to facilitate the formation of stable double emulsions for intestinal drug delivery. Water-in-oil-in-water double emulsions were obtained by a two-step emulsification process and found to be colloidally stable over 6 months allowing permanent encapsulation of a high molecular weight compound (4 kDa fluorescein isothiocyanate-labelled dextran, FD4) in the inner water phase at >90 % encapsulation efficiency. Exposure to simulated gastric conditions and gastric lipase did not affect the emulsion structure or trigger FD4 release. Double emulsions underwent a pronounced restructuring under simulated intestinal conditions due to the presence of bile, yet without triggering excessive FD4 release (<10 %). Digested emulsions reduced the transepithelial electrical resistance of an intestinal in vitro Caco-2 cell culture model by hydrolysis of the emulsion oil phase into medium chain fatty acids that act as intrinsic permeation enhancers. The double emulsions facilitated permeation of FD4 across the intestinal in vitro model at similar levels as non-formulated FD4 and C10. Hence, double Pickering emulsions stabilized by acylated cellulose nanocrystals comprise a novel gastric stable oral delivery system that can co-deliver large hydrophilic macromolecules and permeation enhancers to the small intestine towards effective intestinal absorption.

The ability to predict the absorption of exenatide (Ex), a GLP-1 analogue, after oral dosing to rats in self-nanoemulsifying drug delivery systems (SNEDDS), using in vitro methods, was assessed. Ex was complexed with soybean phosphatidylcholine (SPC) prior to loading into SNEDDS. A design of experiments (DoE) approach was employed to develop SNEDDS incorporating medium-chain triglycerides (MCT), medium-chain mono- and diglycerides (MGDG), Kolliphor® RH40, and monoacyl phosphatidylcholine. SNEDDS with higher proportions of MGDG and Kolliphor® RH40 demonstrated a 9-fold reduction in droplet size (230 to 26 nm), a 1.5-fold decrease in lipolysis (0.23 to 0.34 mmol of FFA), and a 2-fold enhancement in exenatide protection against proteolysis (73 % to 38 %) compared to those with higher MCT content. Permeability studies in Caco-2 cells showed that SNEDDS with higher proportion of MGDG displayed a 40-fold increase in apparent permeability of FD4, when compared to SNEDDS with higher proportion of MCT. An oral gavage study in rats revealed a 1.8-fold higher absorption of Ex in SNEDDS with a higher proportion of MGDG and Kolliphor®RH40 compared to SNEDDS with higher MCT. These results establish a clear in vitro-in vivo correlation, demonstrating that the selected in vitro methods effectively differentiated formulations with high and low absorption of exenatide after oral dosing in rats.

Background: Pediatric patients often receive medicines manipulated from adult formulations due to a lack of age-appropriate products. While such practices are clinically routine, they may reflect deeper systemic deficiencies in pediatric pharmacotherapy. Objective: This scoping review aimed to map the prevalence, definitions, and types of pediatric drug manipulation and to conceptualize manipulation as an indicator of structural gaps in formulation science, regulation, and access. Methods: A systematic search of PubMed (January 2014–July 2024) included 10 studies reporting the frequency of drug manipulation in children aged ≤18 years. Eligible studies were synthesized narratively according to PRISMA-ScR guidelines. Results: Ten studies from nine countries were included, reporting manipulation frequencies ranging from 6.4% to 62% of all drug administrations and up to 60% at the patient level. Manipulated formulations most commonly included oral solid doses, altered through dispersing, splitting, or crushing. Definitions and methodologies varied considerably. The findings revealed five recurring structural gaps: limited pediatric formulations, inconsistent regulatory implementation, lack of standardized definitions and guidance, insufficient evidence on manipulation safety, and inequitable access across regions. Conclusion: Manipulation of finished dosage forms for use in children is a widespread, measurable phenomenon reflecting systemic inadequacies in formulation development, regulation, and access. Recognizing manipulation as a structural indicator may guide policy, innovation, and equitable pediatric pharmacotherapy worldwide.

Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) have emerged as a promising approach to increase the drug load of hydrophobic molecules, compared to conventional SNEDDS (con-SNEDDS). This study aimed to explore the relationship between equilibrium solubility (Seq) and the maximum supersaturation concentration (CSmax) in SNEDDS preconcentrates for three model drugs: carvedilol (CVL), ritonavir (RTV) and nilotinib (NTB). The emulsion droplet size of con-SNEDDS (90 % of Seq) and super-SNEDDS (90 % of CSmax), and the influence of polyvinylpyrrolidone-vinyl acetate copolymers 64 (PVP/VA 64) was assessed, as well as the relationship between physical stability and viscosity of super-SNEDDS in the presence of PVP/VA 64. A Design of Experiment (DoE) approach was applied to optimize SNEDDS compositions. The results showed linear correlations between Seq and CSmax across all three model drugs, leading to a consistent (but drug dependent) maximum degree of supersaturation (DSmax) (CVL = 2.49, RTV = 4.56, NTB = 2.54) within the DoE design space. Dissolving 4 % (w/w) PVP/VA 64 in the SNEDDS preconcentrates did not influence the described correlations or DSmax. Emulsion droplet size remained unchanged upon drug loading to 90 % of Seq (con-SNEDDS) compared to drug-free SNEDDS. Further loading to 90 % of CSmax (super-SNEDDS) also resulted in negligible size changes in emulsions with initial droplet sizes below 60  nm, whereas those above 60  nm exhibited pronounced droplet size increase, following a quadratic relationship compared with their initial con-SNEDDS droplet size. Incorporation of PVP/VA 64 enhanced both the physical stability and viscosity of super-SNEDDS; however, only a weak correlation was observed between these two parameters, suggesting that viscosity alone did not govern the stabilization of super-SNEDDS. In summary, within the design space, DSmax is drug-dependent, but independent of SNEDDS composition or polymer addition; droplet size of super-SNEDDS is dependent on both drug and SNEDDS composition, but is unaffected by polymer; in contrast, physical stability is jointly influenced by drug properties, SNEDDS composition, and polymer addition.

Development of co-amorphous systems (CAMS) of griseofulvin (GRI) with three amino acids (AAs) - L-lysine (GRI/LYS), L-methionine (GRI/MET), and L-valine (GRI/VAL) was investigated using the established methods of feed solvent pretreatment hot melt extrusion (mHME), ball milling (BM; dry and liquid-assisted), quench cooling (QC), and solvent evaporation (SE). The role of solvent treatment and thermal stress in mHME was elucidated. CAMS formation was evaluated using crystallography (XRPD) and modulated differential scanning colorimetry (DSC). Successful CAMS development was possible only with mHME emphasizing the importance of thermal stress. Hydrogen bonding was identified spectroscopically (ATR-FTIR) in the mHME and SE products by the disappearance of the 1658 cm-1 FTIR carbonyl peak indicating the important role of AcOH in feed pretreatment. Structural relaxation time of the developed CAMS was studied using thermal activity monitoring (TAM). Johari-Goldstein (β) secondary relaxation temperature was estimated using dynamic mechanical analysis (DMA). The structural relaxation time (τDβ), and the secondary relaxation temperature (Tgβ) of the developed CAMS increased in the order GRI/LYS < GRI/MET < GRI/VAL. Significant correlations exist between Tgβ and τDβ (R2 = 0.9922), and between Tgβ and the Hansen solubility parameters (R2 = 0.9965). The results of the in vitro dissolution/permeability test using the MicroFLUX™ system, in which the donor and receiver compartments are separated by a lipophilic membrane/hydrophilic filter barrier showed that GRI/VAL and GRI/MET CAMS gave significantly higher release and permeability compared to amorphous drug alone, due to the superior dissolution and sustained supersaturation.

This study aimed to evaluate if the Dynamic Gastrointestinal Model (DGM) is able to simulate the gastro-resistant behavior of Capsugel® Enprotect® capsules under physiologically relevant fasted and fed states. Enprotect® capsules were filled with a caffeine powder blend and tested under three conditions: fasted state, a light meal (∼500 kcal), and a high-fat meal (∼900 kcal). Results showed that the capsules remained intact in the stomach across all conditions and released their contents only after intestinal entry. Dissolution and pharmacokinetic predictions closely aligned with published clinical data for the fasted state and light meal. The extended gastric residence and elevated pH of the high-fat meal did not compromise capsule integrity possibly due to a combination of capsule floating and acid pocket formation on the top of the digesting meal. These findings confirm the robustness of Enprotect® capsules and demonstrate the utility of the DGM in predicting oral dosage form behavior and performance under physiologically relevant gastrointestinal conditions.

The pharmacokinetics (PK) of oral drug compounds are often significantly altered by food intake and evaluating this effect, as required by regulatory agencies, typically involves costly and time-consuming clinical trials. This study used the Dynamic Gastrointestinal Model (DGM), an advanced in vitro system simulating both biochemical and mechanical aspects of the human upper gastrointestinal tract, to predict plasma concentration-time profiles (PK profiles) and food effect of three immediate release oral drug products. The drug products, containing cinnarizine (CIN), diclofenac potassium (DIC) or paracetamol (PAR), were processed in the DGM mimicking the fasted and fed state clinical protocols and the resulting intestinal drug dissolution profiles were modelled (by convolution) to achieve the predicted PK profiles. The predicted PK profiles in both the fasted and fed state were in accordance with the observations in clinical trials, capturing both the positive food effect for CIN and the negative food effects for DIC and PAR. These findings demonstrate the ability of the DGM to provide insights into the PK performance and food effect of oral drug products.

Quince seed mucilage, as a polymer, has been studied for tailoring drug delivery systems for pH-specific drug release. The antidiabetic properties of this polymer are well studied, but its effect in drug carrier systems is unknown in diabetes therapy. Quince seed mucilage comprising hybrid calcium carbonate composites loaded with metformin was developed via coprecipitation technique to assess their effectiveness in diabetes treatment. They were evaluated for entrapment efficiency, in vitro release profile, surface morphology, and other physicochemical characterizations. The in vivo assessment was conducted for 28 days in diabetic rats to monitor blood glucose levels and body weight. The developed composites exhibited a sustained in vitro release profile, where the drug release was slow and pH-dependent with optimum entrapment efficiency (82%). The surface morphology study revealed a homogeneous rhombohedral structure of developed composites. Moreover, the animal study signifies the blood glucose-lowering effect of developed composites which was 9.49% for blank composites and 65.7% for metformin-loaded composites after 28 days in diabetic rats. Furthermore, metformin-loaded composites were able to significantly revive the body weight reduction in diabetic rats as compared to the drug solution. These composites improved body weight and blood glucose levels in in vivo studies as compared to the control group, indicating their potential application in drug delivery. This study provides new insights into diabetes research and introduces a carrier system that assists in diabetes management in conjunction with the drug.

The role of intraluminal enzymes for the hydrolysis of active pharmaceutical ingredients (API), prodrugs and pharmaceutical excipients will be reviewed. Carboxylesterases may hydrolyze ester-based API, prodrugs and ester-bond containing polymer excipients, whereas lipases digest lipid formulation excipients, such as mono-, di- and triglycerides. To clarify the conditions that should be mimicked when designing in vitro studies, we briefly review the upper gastrointestinal physiology and provide new data on the inter-individual variability of enzyme activities in human intestinal fluids. Afterwards, the methodology for studying enzymatic hydrolysis of API, prodrugs, lipid and polymeric excipients, as well as the main results that have been obtained, are summarized. In vitro digestion models used to characterize lipid formulations are well described, but data about the hydrolysis of lipid excipients (including surfactants) has been scarce and contradictory. Data on API and prodrug hydrolysis by esterases is available; however, inconsistent use of enzyme types and concentrations limits structure-stability relationships. Hydrolysis of polymer excipients in the lumen has not been significantly explored, with only qualitative data available for cellulose derivates, polyesters, starches, etc. Harmonization of the methodology is required in order to curate larger enzymatic hydrolysis datasets, which will enable mechanistic understanding and theoretical prediction.

Current treatment strategies are moving towards patient-centricity, which emphasizes the need for new solutions allowing for medication tailored to a patient. This can be realized by precision medicine where patient diversity is considered during treatment. However, the broader use of precision medicine is restricted by the current technological solutions and rigid manufacturing of pharmaceutical products by mass production principles. Additive manufacturing of pharmaceutical products can provide a feasible solution to this challenge. In this review, a particular subtype of additive manufacturing, that is, binder jetting 3D printing, is introduced as a solution for fabricating pharmaceutical solid products that can be considered as precision medicine. Technical aspects, practical applications, unique advantages and challenges related to this technique are discussed, indicating that binder jetting 3D printing possesses the potential for fabricating already new product prototypes, where diversity in patient treatment in terms of the needs for specific drug type, dose and drug release can be accounted. To further advance this type of mass customization of pharmaceuticals, multidisciplinary research initiatives are needed not only to cover the engineering aspects but also to bridge these innovations with patient-centric perspectives.

This study aimed to develop chitosan alginate nanoparticles (CANPs) for enhanced stability for dermal delivery of protein hydrolysate from Acheta domesticus (PH). CANPs, developed using ionotropic pre-gelation followed by the polyelectrolyte complex technique, were characterized for particle size, polydispersity index (PDI), and zeta potential. After the incorporation of PH into CANPs, a comprehensive assessment included encapsulation efficiency, loading capacity, morphology, chemical analyses, physical and chemical stability, irritation potential, release profile, skin permeation, and skin retention. The most optimal CANPs, comprising 0.6 mg/mL sodium alginate, 1.8 mg/mL calcium chloride, and 0.1 mg/mL chitosan, exhibited the smallest particle size (309 ± 0 nm), the narrowest PDI (0.39 ± 0.01), and pronounced negative zeta potential (−26.0 ± 0.9 mV), along with an encapsulation efficiency of 56 ± 2%, loading capacity of 2.4 ± 0.1%, release of 40 ± 2% after 48 h, and the highest skin retention of 12 ± 1%. The CANPs induced no irritation and effectively enhanced the stability of PH from 44 ± 5% of PH remaining in a solution to 74 ± 4% after three-month storage. Therefore, the findings revealed the considerable potential of CANPs in improving PH stability and skin delivery, with promising applications in cosmetics and related fields.

Background/Objectives: This study aims to broaden the knowledge on co-amorphous phospholipid systems (CAPSs) by exploring the formation of CAPSs with a broader range of poorly water-soluble drugs, celecoxib (CCX), furosemide (FUR), nilotinib (NIL), and ritonavir (RIT), combined with amphiphilic phospholipids (PLs), including soybean phosphatidylcholine (SPC), hydrogenated phosphatidylcholine (HPC), and mono-acyl phosphatidylcholine (MAPC). Methods: The CAPSs were initially prepared at equimolar drug-to-phospholipid (PL) ratios by mechano-chemical activation-based, melt-based, and solvent-based preparation methods, i.e., ball milling (BM), quench cooling (QC), and solvent evaporation (SE), respectively. The solid state of the product was characterized by X-ray powder diffraction (XRPD), polarized light microscopy (PLM), and differential scanning calorimetry (DSC). The long-term physical stability of the CAPSs was investigated at room temperature under dry conditions (0% RH) and at 75% RH. The dissolution behavior of the CCX CAPS and RIT CAPS was studied. Results: Our findings indicate that SE consistently prepared CAPSs for CCX-PLs, FUR-PLs, and RIT-PLs, whereas the QC method could only form CAPSs for RIT-PLs, CCX-SPC, and CCX-MAPC. In contrast, the BM method failed to produce CAPSs, but all drugs alone could be fully amorphized. While the stability of each drug varied depending on the PLs used, the SE CAPS consistently demonstrated the highest stability by a significant margin. Initially, a 1:1 molar ratio was used for screening all systems, though the optimal molar ratio for drug stability remained uncertain. To address this, various molar ratios were investigated to determine the ratio yielding the highest amorphous drug stability. Our results indicate that all systems remained physically stable at a 1.5:1 ratio and with excess of PL. Furthermore, the CAPS formed by the SE significantly improves the dissolution behavior of CCX and RIT, whereas the PLs provide a slight precipitation inhibition for supersaturated CCX and RIT. Conclusions: These findings support the use of a 1:1 molar ratio in screening processes and suggest that CAPSs can be effectively prepared with relatively high drug loads compared to traditional drug–polymer systems. Furthermore, the study highlights the critical role of drug selection, the preparation method, and the PL type in developing stable and effective CAPSs.

Acheta domesticus is an edible insect, rich in nutritional value and considered a sustainable protein source. This study aimed to investigate the potential application of A. domesticus extracts for anti-skin-aging purposes. The extracts were prepared by maceration at ambient temperature with 95% ethanol or hexane and maceration in gentle heat (45 °C) with 95% v/v ethanol or DI water. The extracts were examined for total protein, phenolic, and flavonoid contents. Protein molecular weight distribution was analyzed. The safety of the extracts was investigated in terms of irritation and cytotoxicity. Biological activities relevant to the inhibition of skin aging were evaluated, including increasing transforming growth factor-beta 1 (TGF-β1) expression and inhibitory activities on collagenase and hyaluronidase. The aqueous extract from maceration in gentle heat had the highest total protein content (63 ± 1% w/w), total phenolic content (0.48 ± 0.03 mg GAE/g extract), TGF-β1 stimulating activities (33 ± 2 pg/mL), and collagenase inhibition (with a half maximal inhibitory concentration of 26 ± 1 µg/mL) among various extracts investigated. It caused no irritation to the hen’s egg chorioallantoic membrane and showed no cytotoxicity to human dermal fibroblasts and peripheral blood mononuclear cells. Therefore, aqueous A. domesticus extract is proposed as an innovative natural anti-skin-aging ingredient.