Hydrophilic Model Drug Research Articles

Ferric ions crosslinked hyaluronic acid beads: potentials for drug delivery use

Introduction and purpose Despite the attractive properties of hyaluronic acid (HA), The preparation of HA beads is still challenging. This article reports the preparation of pH-sensitive gel HA beads. The ionic gelation method was used to prepare the HA gel beads using ferric ions. This cross-linking type is based on forming coordination bonds, which enhance the mechanical properties of the prepared beads. Methods The developed beads were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) examined the bead’s morphology. Furthermore, the potential of HA gel beads as an oral drug delivery system was investigated using metformin as a hydrophilic model drug. The entrapment efficiency and in vitro, release, and release kinetics were evaluated. The crosslinking density and HA concentration effect on drug release and bead swelling capacity under pH 1.2 and 7.4 were also investigated. Results The entrapment efficiency of metformin in HA beads was found to be 79.56 ± 3.89%. FTIR analysis indicated the ionic interaction between ferric ions and the carboxylic groups on the HA molecule. At the same time, there was no substantial interaction between metformin and the polymeric bead. Morphological evaluation and DSC analysis suggested the successful incorporation of metformin within the beads. The in vitro drug release evaluation showed pH-dependent extended release where the release kinetics followed the first-order mathematical model. Conclusions This study provides a value-added formulation with the potential for drug delivery use, which can be further investigated for biomedical applications.

Vesicular phospholipid gels: A new strategy to improve topical antimicrobial dermatotherapy

Therapeutically effective and biocompatible dermal formulations that can ensure localization of a high level of antimicrobial drug at the site of action for an appropriate duration, while at the same time providing intrinsic reepithelization properties, are of particular importance for the treatment of infected and injured skin. The current research aimed to explore the potentials of using vesicular phospholipid gels (VPGs), semisolid formulations consisting of tightly packed liposomes (100–––200 nm), as innovative local depot drug vehicles for advanced topical dermatotherapy. Ciprofloxacin hydrocholoride (CPX) was selected as a model hydrophilic antibacterial drug and was loaded into several VPGs, differing in their composition. Various CPX-loaded VPGs (CPX-VPGs) were evaluated in vitro for the rheological and physicochemical characteristics, drug release profile, stability under in vivo mimicked conditions and during storage, skin permeability, biocompatibility with the epidermal cells, antibacterial efficacy and wound healing assay, to determine the optimal CPX-VPG for topical dermatotherapy. Viscosity and bilayers fluidity of VPGs affected the release of CPX from CPX-VPGs and its skin localization, limiting CPX percutaneous absorption. All CPX-VPGs exhibited even a 2-fold increase in anti-biofilm activity against both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolate compared to the free drug, while showing no toxic effects on human keratinocytes in vitro. Based on the pronounced proliferative effects on keratinocytes, superior in vitro wound healing effect and drug localization on/inside the skin, CPX-VPGs containing chitosan and hydrogenated phospholipid proved to be the most promising for topical dermatotherapy. These findings, along with increased bioadhesiveness and the slow drug release, with CPX concentrations significantly above the minimum biofilm inhibitory concentrations for bacteria typical in infected wounds, would contribute not only to the improvement of the antimicrobial dermatotherapy, but also to reduction of the frequency of the drug administration.

Utilizing Food Waste in 3D-Printed PLA Formulations to Achieve Sustainable and Customizable Controlled Delivery Systems.

This is the first study that explores blending polylactic acid (PLA) with various biomasses, including food wastes-brewer's spent grain (BSG), spent coffee grounds (SCG), sesame cake (SC), and thermoplastic starch (TPS) biomass to create composite gastric floating drug delivery systems (GFDDS) through 3D printing. The aim is to investigate the influence of biomass percentage, biomass type, and printing parameters on their corresponding drug release profiles. 3D-printed (3DP) composite filaments were prepared by blending biomasses and PLA before in vitro drug release studies were performed using hydrophilic and hydrophobic model drugs, metoprolol tartrate (MT), and risperidone (RIS). The data revealed that release profiles were influenced by composite compositions and wall thicknesses of 3DP GFDDS capsules. Up to 15% of food waste could be blended with PLA for all food waste types tested. Delivery studies for PLA-food wastes found that MT was fully released by 4 h, exhibiting burst release profiles after a lag time of 0.5 to 1.5 h, and RIS could achieve a sustained release profile of approximately 48 h. PLA-TPS was utilized as a comparison and demonstrated variable release profiles ranging from 8 to 120 h, depending on the TPS content. The results demonstrated the potential for adjusting drug release profiles by incorporating affordable biomasses into GFDDS. This study presents a promising direction for creating delivery systems that are sustainable, customizable, and cost-effective, utilizing sustainable materials that can also be employed for agricultural, nutraceutical, personal care, and wastewater treatment applications.

Chitosan-Type-A-Gelatin Hydrogels Used as Potential Platforms in Tissue Engineering for Drug Delivery.

Hydrogels are materials made of crosslinked 3D networks of hydrophilic polymer chains that can absorb and retain significant amounts of water due to their hydrophilic structure without being dissolved. In relation to alternative biomaterials, hydrogels offer increased biocompatibility and biodegradability, giving them distinct advantages. Thus, hydrogel platforms are considered to have the potential for the development of biomedical applications. In this study, the main objective was the development of hybrid hydrogels to act as a drug delivery platform. These hydrogels were made from chitosan (CH) and type A gelatin (G), two natural polymers that provide a supportive environment for cellular attachment, viability, and growth, thanks to their unique properties. Particularly, the use of gelatins for drug delivery systems provides biodegradability, biocompatibility, and non-toxicity, which are excellent properties to be used in the human body. However, gelatins have some limitations, such as thermal instability and poor mechanical properties. In order to improve those properties, the aim of this work was the development and characterization of hybrid hydrogels with different ratios of CH-G (100-0, 75-25, 50-50, 25-75, 0-100). Hydrogels were characterized through multiple techniques, including Fourier transform infrared (FTIR) spectroscopy, rheological and microstructural studies, among others. Moreover, a model hydrophilic drug molecule (tetracycline) was incorporated to evaluate the feasibility of this platform to sustain the release of hydrophilic drugs, by being tested in a solution of Phosphate Buffer Solution at a pH of 7.2 and at 37 °C. The results revealed that the synergy between chitosan and type A gelatin improved the mechanical properties as well as the thermal stability of it, revealing that the best ratios of the biopolymers are 50-50 CH-G and 75-25 CH-G. Thereby, these systems were evaluated in a controlled release of tetracycline, showing a controlled drug delivery of 6 h and highlighting their promising application as a platform for controlled drug release.

Synchronized Codelivery of Combination Chemotherapies Intratumorally Using a Lipidic Lyotropic Liquid Crystal System.

In this work, an injectable in situ depot-forming lipidic lyotropic liquid crystal (L3C) system is developed to codeliver a precisely synchronized combination of chemotherapeutics intratumorally. The developed L3C system is composed of amphiphilic lipids and surfactants, including monoolein, phosphatidylcholine, tocopherol acetate, and d-α-tocopherol polyethylene glycol 1000 succinate. Owing to its amphiphilic nature, the developed formulation can coaccommodate both hydrophobic and hydrophilic chemotherapeutic moieties simultaneously. The study presents a proof of concept by designing a combination chemotherapy regimen in vitro and demonstrating its in vivo translation using doxorubicin and paclitaxel as model hydrophilic and hydrophobic drug moieties, respectively. The synchronized combination of the two chemotherapeutics with maximum synergistic activity was identified, coloaded in the developed L3C system at predefined stoichiometric ratios, and evaluated for antitumor efficacy in the 4T1 breast tumor model in BALB/c mice. The drug-loaded L3C formulation is a low-viscosity injectable fluid with a lamellar phase that transforms into a hexagonal mesophase depot system upon intratumoral injection. The drug-loaded depot system locally provides sustained intratumoral delivery of the chemotherapeutics combination at their precisely synchronized ratio for over a period of one month. Results demonstrate that the exposure of the tumor to the precisely synchronized intratumoral chemotherapeutics combination via the developed L3C system resulted in significantly higher antitumor activity and reduced cardiotoxicity compared to the unsynchronized combination chemotherapy or the synchronized but uncoordinated drug delivery administered by a conventional intravenous route. These findings demonstrate the potential of the developed L3C system for achieving synchronized codelivery of the chemotherapeutics combination intratumorally and improving the efficacy of combination chemotherapy.

Agile quality-by-design development of alginate microparticles for encapsulation of hydrophilic drug

The development of alginate microparticles for encapsulation of hydrophilic drug is addressed. The alginate microparticles are produced by the emulsification/gelation process. The objective of this study is to optimize the encapsulation of sunset yellow, a model of small hydrophilic drug, by the means of an agile quality by design (QbD) approach. Five input factors are considered: the alginate concentration (2–7% w/V), the drug/polymer ratio (0.1/1–0.5/1), the cross-linker addition flow rate (1–1.6 mL/min), the cross-linker volume (5–10 mL), and the crosslinking time (15–60 min). Critical quality attributes (and their associated specifications) are the particle size (∈30;150µm) and polydispersity, the encapsulation efficiency (>50%), and the drug loading (>10%). The implemented agile method follows three successive QbD sprints, each based on a specific design of experiments (DoE). First, a screening of the process parameters is performed using a Plackett-Burman design, followed in a second sprint by the implementation of a central composite Hartley’s design to identify the design space and to extract four eligible control operating regions where the probability to meet the CQA specifications is above 95%. In the last sprint, one of these optimal operating conditions has been qualified by testing eight end points of the region through the application of a full factorial design. This operating region corresponds to a combination of three factors: alginate concentration in [6.7;7]%, drug/polymer ratio in [0.29;0.34]w/w and a curing time in [40;60]min.

Synthesis of α,ω-bis-Mercaptoacyl Poly(alkyl oxide)s and Development of Thioether Cross-Linked Liposome Scaffolds for Sustained Release of Drugs.

With the aim to develop novel scaffolds for the sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt)-protected mercapto acids, followed by the removal of the acid labile S-Mmt group. This method allowed for the efficient synthesis of the title compounds in high yield and purity, which were further used in the development of a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with pre-formed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed for real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nano-sized characteristics of the initial liposomes and allowed for the sustained release of calcein (which was used as a hydrophilic dye and a hydrophilic drug model), providing evidence for the efficient synthesis of a novel drug release scaffold consisting of nanoliposome building blocks.

W/O/W Microemulsions for Nasal Delivery of Hydrophilic Compounds: A Preliminary Study

The administration of hydrophilic therapeutics has always been a great challenge because of their low bioavailability after administration. For this purpose, W/O/W microemulsion resulted to be a potential successful strategy for the delivery of hydrophilic compounds, interesting for the nasal mucosal therapy. Herein, an optimized biphasic W/O microemulsion was designed, through a preliminary screening, and it was inverted in a triphasic W/O/W microemulsion, intended for the nasal administration. In order to enhance the mucosal retention, surface modification of the biphasic W/O microemulsion was performed adding didodecyldimethylammonium bromide, and then converting the system into a cationic triphasic W/O/W microemulsion. The developed samples were characterized in terms of droplet size, polydispersity, zeta potential, pH and osmolality. The physical long-term stability was analyzed storing samples at accelerated conditions (40 ± 2 °C and 75 ± 5 % RH) for 6 months in a constant climate chamber, following ICH guidelines Q1A (R2). In order to verify the potential retention on the nasal mucosa, the two triphasic systems were analyzed in terms of mucoadhesive properties, measuring the in vitro interaction with mucin over time. Furthermore, fluorescein sodium salt was selected as a model hydrophilic drug to be encapsulated into the inner core of the two triphasic W/O/W microemulsions, and its release was analyzed compared to the free probe solution. The cytocompatibility of the two platforms was assessed on two cell lines, human fibroblasts HFF1 and Calu-3 cell lines, chosen as pre-clinical models for nasal and bronchial/tracheal airway epithelium.

Incorporating surfactants into PCL microneedles for sustained release of a hydrophilic model drug

Polymeric microneedles (MNs) are widely used for sustained drug release due to their distinct advantages over other types of MNs. Poly-ε-caprolactone (PCL) stands out as a biodegradable and biocompatible hydrophobic polymer commonly employed in drug delivery applications. This study explores the impact of surfactants on the encapsulation and release rate of a model hydrophilic drug, minoxidil (MXD), from PCL MNs. Three nonionic surfactants, Tween 80, Span 60, and polyethylene glycol (PEG), were integrated into PCL MNs at varying concentrations. Compared to the other types of surfactants, PEG-containing PCL MNs exhibit enhanced insertion capabilities into a skin-simulant parafilm model and increased mechanical strength, suggesting facile penetration into the stratum corneum. Furthermore, MXD-PEG MNs show the highest encapsulation efficiency and are further characterized using FTIR, DSC and XRD. Their mechanical strength against different static forces was measured. The MNs exhibit a sustained release pattern over 20 days. Eventually, MXD-PEG MNs were subjected to penetration testing using chicken skin and required minimal insertion forces with no observed MN failure during experimentation even after compression with the maximum force applied (32 N per patch). Taken together, the present work demonstrates the feasibility of incorporating nonionic surfactants like PEG into the tips of hydrophobic PCL MNs for sustained delivery of a model hydrophilic drug. This formulation strategy can be used to improve patient compliance by allowing self-administration and achieving prolonged drug release.

Double Emulsions Stabilized by PGPR and Arabic Gum as Capsules: The Surprising Stabilizing Role of Inner Droplets.

The encapsulation efficiency and stability over time of either vitamin B12, a model hydrophilic drug, or an aqueous suspension of Cydia pomonella granulovirus (CpGV), which is a biopesticide, using a water-in-sunflower oil-in-water (W1/O/W2) double emulsion, are studied. Two antagonistic stabilizers are used to prepare the double emulsion: the mainly lipophilic polyglycerol polyricinoleate (PGPR) and the mainly hydrophilic polysaccharide Arabic gum (AG). Combining ultraviolet-visible (UV-visible) titration, rheology, and oil globule size measurement allows assessing drug release, emulsion elasticity, and globule evolution as a function of time. A stability diagram is plotted as a function of two determining parameters: the nonadsorbed PGPR concentration in the oil and the inner water droplet fraction. To understand the presence of the nonstability domains, the influence of the two identified parameters on the outermost interfacial tension is examined. Surprisingly, the inner water drop volume fraction exhibits a stabilizing phenomenon that is discussed in terms of interfacial shielding to PGPR adsorption.

Harnessing the power of thermosensitive liposomes with gold nanoprisms and silica for controlled drug delivery in combined chemotherapy and phototherapy.

In recent years, the scientific community has tried to address the treatment of complex diseases such as cancer in a more appropriate and promising way. Regarding this and benefiting from the unique optical properties of gold nanoprisms (AuNPRs), the physicochemical properties of thermosensitive liposomes (TSLs), and the tunable drug encapsulation and release properties of silica nanoparticles (BioSi@NPs), this study has developed two nanoformulations. These nanoformulations have the potential to integrate chemotherapy and photothermal therapy within a single entity. Once their components were synthesized and characterized separately, two strategies were taken in order to develop these multifunctional nanoformulations: (1) covalent binding of AuNPRs to TSLs and (2) co-encapsulation of both components within BioSi@NPs, without modifying the optical and physicochemical properties of AuNPRs and TSLs. Finally, the suitability of both nanoformulations to carry and release hydrophilic drugs when triggered by a 1064 nm NIR laser has been explored by using the fluorescent probe 5(6)-carboxyfluorescein (CF) as a hydrophilic drug model. Different laser power and time of exposure were also tested evidencing that hydrophilic drugs were only released from TSLs in the presence of AuNPRs and that the drug release profile was dependent on the type of nanoformulation and irradiation conditions used. In conclusion, these multifunctional nanoformulations exhibit promising potential for controlled drug delivery in combined chemotherapy and phototherapy, with the capability to precisely control the release kinetics based on specific therapeutic needs.

The use of polymorphic state modifiers in solid lipid microparticles: The role of structural modifications on drug release performance

This study investigates the correlation between the structural and release properties of solid lipid microparticles (MPs) of tristearin containing 5 % w/w of four different liquid additives used as crystal modifiers: isopropyl myristate (IM), ethyl oleate (EO), oleic acid (OA) and medium chain triglycerides (MCT). All additives accelerated the conversion of the unstable α-form of tristearin, formed after the MPs manufacturing, to the stable β-polymorph and the transformation was completed within 24 h (for IM and EO) or 48 h (for OA and MCT). The kinetic of polymorphic transition at 25 °C was investigated by simultaneous synchrotron SAXS/WAXS and DSC analysis after melting and subsequent cooling of the lipid mixture. After crystallization in the α-phase, additives accelerate the solid-solid phase transformation to β-tristearin. SAXS data showed that two types of structural modifications occurred on MPs during storage: compaction of the crystal packing (slight decrease in lamellar thickness) and crystal growth (increased number of stacked lipid lamellae). The release behavior of a model hydrophilic drug (caffeine) at two different amounts (15 % and 30 %) from MPs was studied in water and biorelevant media simulated the gastric and intestinal environment. It was particularly significant that the introduction of IM, EO and MCT were able to prolong the drug release in water, passing from a diffusion-based Higuchi kinetics to a perfect zero-order kinetic. Moreover, the overall release profiles were higher in biorelevant media, where erosion/digestion of MPs was observed. After 6 months, a moderate but statistically significant change in release profile was observed for the MPs with IM and EO, which can be correlated with the time-dependent structural alterations (i.e. larger average crystallite size) of these formulations; while MPs with OA or MCT displayed stable release profiles. These findings help to understand the correlation between release behavior, polymorphism and supramolecular‐level structural modification of lipid formulations containing crystal modifiers.

Fluorescent hydrophobic ion pairs: A powerful tool to investigate cellular uptake of hydrophobic drug complexes via lipid-based nanocarriers

Hypothesis: Hydrophobic ion pairs (HIPs) between two fluorescent components and incorporation into nanoemulsions (NE) allows tracking in cellular uptake studies.Experiments: HIPs were formed between propidium iodide and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2–1,3-benzoxadiazol-4-yl) (NBD-PE), azure A chloride and NBD-PE or coumarin 343 and 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide) (DiA). Fluorescence spectra of the resulting complexes were recorded. HIPs were loaded into zwitterionic NE and their size, stability in different media, haemolytic properties and cytotoxicity were evaluated. Furthermore, cellular uptake at 37 °C and 4 °C was investigated via flow cytometry and confocal microscopy.Findings: HIP-formation increased lipophilicity of the hydrophilic model drugs. NE exhibited a size between 80 and 150 nm and were not toxic in concentrations up to 0.1 % but showed high haemolytic properties. Cellular uptake of propidium, azure A and coumarin 343 were 8-fold, 115-fold and 1.3-fold improved by the formation of HIPs and up to 59-fold, 120-fold and 50-fold by incorporating these HIPs in NE, respectively. Lower uptake was observed at 4 °C. In case of propidium/ NBD-PE and azure A/ NBD-PE HIPs, propidium and azure A were delivered into the cytosol, whereas NBD-PE was unable to enter cells. In case of coumarin 343/ DiA HIPs, both components accumulated in the cell membrane. Therefore, HIPs between two fluorescent compounds are a powerful tool to investigate cellular uptake of hydrophobic complexes via nanocarriers by visualization of their cellular distribution.

Thermosensitive Hydrogel-Functionalized Mesoporous Silica Nanoparticles for Parenteral Application of Chemotherapeutics.

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own, or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on-demand drug release. In this study, a hybrid nanosystem for temperature- and pH-sensitive delivery was prepared from MCM-41 nanoparticles grafted with a newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemically modified by the attachment of carboxyl groups. Later, they were grafted with agar (AA) and vinylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hydrophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in media with different pH and at different temperatures. Under tumour simulating conditions (40 °C and pH 4.0), doxorubicin was almost completely released within 72 h. The biocompatibility of the proposed nanoparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanoparticles for temperature-sensitive and pH-triggered drug delivery at the tumour site.

Fabrication of PEG-PLGA Microparticles with Tunable Sizes for Controlled Drug Release Application.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5-50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5-7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications.

Tuning stimuli-responsive properties of alginate hydrogels through layer-by-layer functionalization for dual-responsive dual drug release

This study aimed to understand the effect of layer-by-layer (LbL) modification on the stimuli-responsive properties of physical alginate (ALG) hydrogels and examine the potential of LbL-coated hydrogels as dual responsive, dual drug releasing platforms for antibacterial applications. ALG hydrogels were functionalized through LbL self-assembly using temperature-responsive poly(2-isopropyl-2-oxazoline) (PiPOX) and pH-responsive tannic acid (TA). Ciprofloxacin (CIP) and Curcumin (CUR) were used as model hydrophilic and hydrophobic drugs, respectively. CIP was included in the hydrogel during LbL process, whereas CUR was incorporated into the hydrogel through gelation in the presence of CUR-loaded CaCO3 microparticles. The effect of LbL modification on the stimuli-responsive swelling, stability and drug release properties of hydrogels was examined in comparison with bare hydrogels. We have shown that LbL modification resulted in a partial loss of solid content from the hydrogel, leading to a greater swelling. In addition, LbL modification imparted temperature-responsiveness to ALG hydrogel and provided enhanced CIP release upon increasing the temperature at pH 7.4. On the other hand, LbL-coated hydrogels displayed minimal CIP release at pH 5.5 regardless of the temperature. The antibacterial activity of LbL-coated hydrogels was greater at pH 7.4 than pH 5.5 against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The combination of CIP and CUR provided enhanced antibacterial effect on the inhibition of E.coli growth at both pH 7.4 and pH 5.5. This effect became more remarkable as the CIP concentration was decreased at a constant CUR concentration in the hydrogels. However, the combinatorial effect of CIP and CUR was not observed with S. aureus. Overall, these results may be promising for wound healing applications where drug release is triggered when the pH becomes alkaline in the presence of bacterial colonization.

Development and characterization of a copolymeric micelle containing soluble and insoluble model drugs.

Micelles are nano-sized particles with a core-shell structure that are made by natural or synthetic polymers or copolymers. The aim of this study was to develop and characterize a copolymeric micelle using two polymers loaded with hydrophilic and lipophilic drugs. Poly(ethylene glycol) and poly(ε-caprolactone) (PEG-PCL) were used to form a copolymeric micelle which was further loaded with either moxifloxacin or clarithromycin as hydrophilic and lipophilic drug samples, respectively. Characterization tests were done including fourier transform-infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, encapsulation efficiency, particle size, zeta potential, polydispersity index, transmission electron microscopy, and in-vitro release test. The construction of the copolymer was confirmed by the results of FT-IR and 1H NMR spectroscopy tests. The encapsulation efficiency test exhibited that loading was about 50% for twelve formulations. Particle size, zeta potential, polydispersity index, and transmission electron microscopy confirmed the formation of monodispersed, uniform, and nano-sized micelles with a few negative charges. The kinetic model of release was fitted to the Higuchi model. Polymeric micelles consisting of PEG-PCL copolymer were loaded with adequate concentrations of hydrophilic (moxifloxacin) and lipophilic (clarithromycin) model drugs, with a mean particle size under 300 nm. Therefore, copolymeric micelles can be used as a suitable drug delivery system for mucous membranes and skin.

Milk-derived exosomes as a promising vehicle for oral delivery of hydrophilic biomacromolecule drugs

Exosomes, as promising vehicles, have been widely used in the research of oral drug delivery, but the generally low drug loading efficiency of exosomes seriously limits its application and transformation. In this study, we systematically investigated the effects of drug loading methods and physicochemical properties (lipophilicity and molecular weight) on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions. Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method, drug lipophilicity, drug molecular weight and exosome/drug proportions. Of note, we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes, which was attributed to the efficient loading capacity and sustained release behavior. Furthermore, milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs (octreotide, exendin-4 and salmon calcitonin). Collectively, our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.

The impact of solvent selection on the characteristics of niosome nanoparticles prepared by microfluidic mixing

The aim of this work was to assess the impact of solvent selection on the characteristics of niosomes prepared by microfluidic mixing. To achieve this, niosomes were manufactured using bench-scale microfluidic mixing systems by changing the type of aqueous and/or organic solvents used to prepare the particles. Niosomes were prepared using different non-ionic surfactants and cholesterol compositions with different solvents and evaluated to investigate the influence of organic and aqueous solvents on the particle's physiochemical characteristics. Here we demonstrated that the solvent selection is a key factor to be considered during the preparation of niosomes with microfluidic mixing. The type of organic solvent was shown to significantly affect the size and the size distribution of the prepared particles. In general, niosome size increased with increasing organic solvent polarity, without affecting the niosomes stability. Moreover, changing the aqueous solvent used to hydrate the lipid components significantly (p < 0.05) affected the characteristics of the prepared niosomes in terms of particles size, size distribution, and surface charge. This impact of solvent selection on the final product is dependent on the lipid components where niosomes prepared with different compositions will have different characteristics when changing the type of organic and/or aqueous solvents. The apparent encapsulation efficiency of quinine as a model hydrophobic drug was subsequently shown to be significantly (p < 0.05) affected by the type of the organic solvent used to prepare the niosomes, while the impact of the organic solvent had less impact on the apparent encapsulation of atenolol as a model hydrophilic drug.

Dermaplaning for Transdermal Drug Permeation Enhancement: A Qualitative and Quantitative Assessment.

In this study, we sought to investigate the effect of dermaplaning, a popular cosmeceutical skin rejuvenation technique on the permeation of drugs. Baclofen and diclofenac were used as hydrophilic and hydrophobic model drugs, respectively. A specific area of skin was treated with 4 strokes of a dermaplane device. Interindividual variability was assessed by having multiple users operate the device for the study. Dermaplaned skin was histologically evaluated and characterized for resistance drop and the depletion of the stratum corneum (SC). The effect of dermaplaning on drug permeation was investigated via in vitro permeation studies. Histology studies depicted the removal of SC and some parts of viable epidermis by dermaplaning. A significant drop in electrical resistance post skin dermaplaning was observed for all treatment groups, signifying the depletion of barrier properties of SC (p < 0.05). Consequently, significant drug flux and permeation were observed over 24h for the model drugs across dermaplaned skin. However, varied absorption profile was observed in vitro for both drugs across dermaplaned skin. Dermaplaning displayed a better suitability for significantly enhancing the permeation of the hydrophilic drug, baclofen. Evidence of variation in results post dermaplaning was observed amidst multiple users as well (p < 0.05).