Cilostazol (CTZ), is a BCS class II drug with limited bioavailability. In the current study, orally disintegrating tablets (ODTs) for buccal delivery of CTZ were prepared by two methods; lyophilization (Lyo-ODTs) and direct compression (DC-ODTs). All CTZ-ODTs were evaluated for in vitro disintegration time (DT) and wetting time (WT) tests, in vitro dissolution. Scanning electron microscopic (SEM) analysis was performed for the selected Lyo-ODT-7 and DC-ODT-2. Lyo-ODT-7 composed of aerosil® 200 and PEG 4000 acquired the shortest DT (13.00 ± 0.14) and WT (33.00 ± 0.26) among the prepared ODTs. It also showed a 2.3 fold significantly enhanced dissolution profile at an early time point (5 min) that was maintained till 1 h, in simulated saliva fluid (pH ∼ 6.8), compared to Pletaal® IR tablets (p < 0.0001). SEM analysis revealed the remarkable porosity of Lyo-ODT-7, confirming its successfully enhanced disintegration and dissolution. Lyo-ODT-7 showed significantly enhanced pharmacokinetic parameters with a 3.5 and 3.6 fold increase in Cmax (p = 0.0493) and AUC0-24 (p = 0.0470), respectively compared to Pletaal® IR tablets. The relative bioavailability of CTZ after buccal administration of Lyo-ODT-7 to rats was 364.45%, compared to the market oral IR tablets; Pletaal®. The enhanced bioavailability imposes the successful oromucosal absorption of CTZ via buccal delivery of Lyo-ODT-7. Our study demonstrated that Lyo-ODT-7 could represent a favorable buccal dosage form for patients with intermittent claudication, suffering from dysphagia. It can also be used in cases of acute cerebral or myocardial infarction due to its significantly enhanced rate and extent of absorption. It is considered a promising approach for buccal delivery of BCS class II active pharmaceutical ingredients (APIs) suffering from solubility problems and hepatic first pass effect.

3D printing is emerging as a transformative technology in pharmaceutical manufacturing, enabling personalized medicine and innovative dosage forms. It allows precise control over drug release and dosage customization, addressing individual patient needs. Various 3D printing techniques, including fused deposition modeling (FDM), are being explored for pharmaceutical applications. The choice of polymers and their rheological properties is crucial for successful extrusion-based printing. While 3D printing accelerates drug development, challenges remain regarding quality control. Quality-by-design (QbD) approaches are essential to ensure safe and effective pharmaceutical products. This study highlights the role of critical process parameters (CPPs), such as infill density and printing speed, in producing poly(lactic acid)-based intravaginal rings. The effects of CPPs on critical quality attributes (CQAs), such as ring dimensions, weight, and swelling degree, were examined. Printing speed (25–100 mm/s) and infill density (0–20%) significantly affected weight and dimensions, with average weights ranging from 0.537 g to 0.629 g. Internal dimensions varied between 9.73 mm and 9.81 mm, while external dimensions ranged from 19.43 mm to 19.69 mm. Rings printed at the lowest speed and highest infill density showed the greatest swelling (2.47%). These findings confirm FDM as a viable method for producing cost-effective, patient-specific intravaginal rings with reproducible results.

Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol–polyvinyl alcohol copolymer (PEG–PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG–PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG–PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG–PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10–12%), and the antimicrobial activity proved effective against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer’s disease drug, to enhance its transport across the blood–brain barrier (BBB). Poly(ethylene glycol)-b-poly(tert-butyl methacrylate) amphiphilic block copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated via colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an in vitro BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer’s treatment by enhancing donepezil’s delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer’s therapy.

Deep eutectic solvents (DESs) are green alternatives to ionic liquids with wide applications in organic synthesis and catalysis. DESs are characterized by being easily prepared, biodegradable, nontoxic, and noninflammable. When one or more of the DES components is active pharmaceutical ingredient (API), the eutectic mixtures are named as therapeutic deep eutectic solvents (THEDESs). THEDESs are prepared in order to improve the solubility and/or the permeability of the APIs. This review presents a brief summary of the most important THEDESs reported to date having antimicrobial and/or anticancer activities. The challenges and limitations of THEDES preparation were also discussed. The work presented here indicated the importance of THEDES as a promising drug delivery system that can overcome the bioavailability problems while retaining or enhancing the biological activity of its components.

The extent and rate of release of active substances from topical products must be sufficient to ensure their effectiveness, which depends on selecting the most appropriate formulation. This study examined allantoin emulsions and gel formulations. In water-in-oil (W/O) and oil-in-water (O/W) emulsions, the main emulsifier was varied, while the same gelling agent was used in all formulations to test the effects of oil phase presence and emulsifier type on allantoin release, as well as the formulations’ rheological and textural characteristics. O/W emulsions exhibited similar release rates and the overall amount released over six hours (11–14.8%), while the highest amount of allantoin (20.9%) was released from the gel formulation. Conversely, the amount of allantoin released from the W/O emulsion (0.77%) was insufficient. Experimental data generally fit best with the Higuchi model kinetics. The formulations demonstrated shear-thinning thixotropic behavior. The greatest deviation from the Newtonian type of flow, with the smallest value of constant n (0.106-0.13) and the largest thixotropic loop area (6602.67-8140 Pas-1) were shown by O/W emulsions. The W/O emulsion exhibited the highest constant n (0.70) and smaller hysteresis area (991.23 Pas-1). Firmness and consistency values increased in the order: gel < W/O emulsion < O/W emulsions. The O/W emulsions showed similarity in microstructure and textural characteristics, likely explaining their similar release behavior.

The electrospinning method involves the production of different drug delivery systems using various polymers. The production of proliposomes with electrospinning provides the hybridization of two novel drug delivery systems. Retinoic acid, also known as all-trans retinoic acid (ATRA), is a common and effective drug for acne therapy. This study aimed to prepare ATRA-loaded proliposomal nanofibers and evaluate their effectiveness on microbial biofilm inhibition. Blank and ATRA-loaded proliposomal nanofiber formulations were fabricated in various polyvinylpyrrolidone, phosphatidylcholine and cholesterol ratios. TEM images verified the rapid formation of the liposomes after the hydration of nanofibers. The vesicle size, polydispersity index and zeta potential values of self-assembled liposomes were measured. The vesicle size values were found to be 321.9–363.8 nm with PDI values varying between 0.332 and 0.511 and zeta potential values of (−16.8) to (−20.5)mV. ATRA-loaded proliposomal nanofibers provided higher bioadhesion (0.25 mJ/cm2) than the commercial cream (0.07 mJ/cm2). The short-term stability results showed that the initial characteristics remained for three months at 4 °C. The proposed ATRA-loaded self-assembled proliposomal system provided antibacterial, fungistatic or fungicidal effects superior to retinoic acid itself and inhibited biofilm formation in lower concentrations. This approach can combine the stability advantage of nanofibers in the dry state with the high effectiveness of liposomes in acne treatment presenting antibacterial and anti-biofilm-forming activity against Candida albicans and Cutibacterium acnes.

Doxorubicin (DOX) is a chemotherapeutic with considerable efficacy, but its application is limited due to cardiotoxicity. Nanoparticles can improve DOX efficacy and prevent its adverse effects. Herein, DOX-loaded extracellular vesicles (DOX-EVs) were prepared using different loading methods including incubation, electroporation, and sonication in different hydration buffers to permeabilize nanostructures or desalinize DOX for improved entrapment. Different protein:drug (µg:µg) ratios of 1:10, 1:5, and 1:2, and incubation parameters were also investigated. The optimal formulation was characterized by western blotting, electron microscopy, Zetasizer, infrared spectroscopy, and release study. The cellular uptake and efficacy were investigated in MCF-7 spheroids via MTS assay, spheroid formation assay (SFA), confocal microscopy, and flow cytometry. The percentage of entrapment efficiency (EE) of formulations was improved from 1.0 ± 0.1 to 22.0 ± 1.4 using a protein:drug ratio of 1:2 and sonication in Tween 80 (0.1%w/v) containing buffer. Characterization studies verified the vesicles’ identity, spherical morphology, and controlled drug release properties. Cellular studies revealed the accumulation and cytotoxicity of DOX-EVs in the spheroids, and SFA and confocal microscopy confirmed the efficacy and cellular localization. Flow cytometry results revealed a comparable and amplified efficacy for DOX-EV formulations with different cell origins. Overall, the EV formulation of DOX can be applied as a promising alternative with potential advantages.

Letrozole (LTZ) is used as first-line treatment for hormone-positive breast cancer (BC) in postmenopausal women. However, its poor aqueous solubility and permeability have reduced its clinical efficacy. Herein, we developed LTZ-nanotransferosomes (LTZ-NT) to address above mentioned issues. The LTZ-NT were optimized statistically using Design Expert® followed by their characterization via dynamic light scattering (DLS), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Differential scanning calorimetry (DSC). The optimized LTZ-NT was incorporated into 1% chitosan-gel to develop LTZ-NTG. Moreover, in vitro drug release and ex vivo permeation of LTZ-NTG were performed and compared with LTZ-dispersion and LTZ-NT. Additionally, skin irritability and histopathology of LTZ-NTG were investigated. Furthermore, in vitro antitumor study of LTZ-NTG was investigated in BC cell lines. The optimized LTZ-NT showed suitable zeta potential (30.4 mV), spherical size (162.5 nm), and excellent entrapment efficiency (88.04%). Moreover, LTZ-NT exhibited suitable thermal behavior and no interactions among its excipients. In addition, LTZ-NTG had an optimal pH (5.6) and a suitable viscosity. A meaningfully sustained release and improved permeation of LTZ was observed from LTZ-NTG. Additionally, LTZ-NTG showed significantly enhanced cell death of MCF-7 and MCC-7 cells. It can be concluded that LTZ-NTG has the potential to deliver chemotherapeutic agents for possible treatment of BC.