The implementation of chatbot-mediated immediacy for synchronous communication in an online chemistry course.

Low student engagement and motivation in online classes are well-known issues many universities face, especially with distance education during the COVID-19 pandemic. The online environment makes it even harder for teachers to connect with their students through traditional verbal and nonverbal behaviours, further decreasing engagement. Yet, addressing such problems with 24/7 synchronous communication is overly demanding for faculty. This paper details an automated Question-Answering chatbot system trained in synchronous communication and instructor immediacy techniques to determine its suitability and effectiveness in attending to students undergoing an online Chemistry course. The chatbot is part of a new wave of affective focused chatbots that can benefit students' learning process by connecting with them on a relatively more humanlike level. As part of the pilot study in the development of this chatbot, qualitative interviews and self-report data capturing student-chatbot interactions, experiences and opinions have been collected from 12 students in a Singaporean university. Thematic analysis was then employed to consolidate these findings. The results support the chatbot's ability to display several communication immediacy techniques well, on top of responding to students at any time of the day. Having a private conversation with the chatbot also meant that the students could fully focus their attention and ask more questions to aid their learning. Improvements were suggested, in relation to the chatbot's word detection and accuracy, accompanied by a framework to develop communication immediacy mechanics in future chatbots. Our findings support the potential of this chatbot, once modified, to be used in a similar online setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s10639-023-11602-1.

Amorphous ternary nanoparticle complex of curcumin-chitosan-hypromellose exhibiting built-in solubility enhancement and physical stability of curcumin.

The low aqueous solubility of curcumin (CUR) had greatly limited the clinical efficacy of CUR therapy despite its well-known potent therapeutic activities. Previously, we developed amorphous nanoparticle complex (nanoplex) of CUR and chitosan (CHI) as a solubility enhancement strategy of CUR by electrostatically-driven drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, (1) lacked a built-in ability to produce prolonged high apparent solubility of CUR in the absence of crystallization-inhibiting agents, and (2) exhibited poor physical stability during long-term storage. For this reason, herein we developed amorphous ternary nanoplex of CUR, CHI, and hypromellose (HPMC) where HPMC functioned as the crystallization inhibitor. The effects of incorporating HPMC on the (1) physical characteristics and (2) preparation efficiency of the CUR-CHI-HPMC nanoplex produced were investigated. Compared to the CUR-CHI nanoplex, the HPMC inclusion led to larger nanoplex (≈300-500 nm) having lower zeta potential (≈1-15 mV) and lower CUR payload (≈40-80%), albeit with higher CUR utilization rates (≈100%) attributed to the CUR interactions with both CHI and HPMC. The CUR-CHI-HPMC nanoplex's physical characteristics could be controlled by varying the HPMC to CHI ratio in the feed. Subsequently, the CUR-CHI-HPMC and CUR-CHI nanoplexes were examined in terms of their (1) storage stability, (2) dissolution characteristics in simulated gastrointestinal fluids, and (3) in vitro solubility enhancement. The results showed that the CUR-CHI-HPMC nanoplex exhibited superior (i) amorphous state stability after twelve-month storage, (ii) dissolution characteristics, and (iii) solubility enhancement in simulated gastrointestinal fluids, with minimal cytotoxicity towards human gastric epithelial cells.

Re-evaluating the presumed superiority of amorphous nanoparticles over amorphous microscale solid dispersion in solubility enhancement of poorly soluble drugs.

The solubility enhancement afforded by amorphous drug nanoparticles was demonstrated in several studies to be superior to the traditional amorphization approach by microscale amorphous solid dispersion (or micro ASD in short). A closer look at these studies, however, revealed that they were performed using a very limited number of poorly-soluble drug models (i.e. itraconazole and cefuroxime). Herein we aimed to re-examine the solubility enhancement and physical stability of amorphous nanoparticles relative to that of the micro ASD using a different poorly-soluble drug model, i.e. ciprofloxacin (CIP). Two types of amorphous CIP nanoparticles, i.e. CIP nanorod prepared by pH-shift precipitation and CIP nanoplex prepared by drug-polyelectrolyte complexation, were compared with CIP micro ASD prepared by spray drying with hydroxypropylmethylcellulose (HPMC). The results showed that (1) the solubility enhancement of amorphous drug nanoparticles was not necessarily superior to that of the micro ASD, particularly in their dry-powder form, and (2) the amorphization strategy of drug nanoparticles significantly influenced their solubility enhancement and physical stability. In short, the solubility enhancement was in the order of CIP micro ASD>CIP nanorod>CIP nanoplex, whereas the amorphous state stability during storage was in the order of CIP nanoplex>CIP micro ASD>CIP nanorod. A trade-off thus existed between the solubility enhancement and physical stability of amorphous CIP particles. The present work concluded that the superior solubility enhancement of amorphous drug nanoparticles was not drug independent.

A new bioavailability enhancement strategy of curcumin via self-assembly nano-complexation of curcumin and bovine serum albumin.

Amorphous drug nanoparticles have recently emerged as a superior bioavailability enhancement strategy for poorly soluble drugs in comparison to the conventional microscale amorphous solid dispersions. In particular, amorphous drug nanoparticle complex (or nanoplex) represents an attractive bioavailability enhancement strategy of curcumin (CUR) - a medicinal herb known for its wide-ranging therapeutic activities - attributed to the high payload, cost-effective preparation, and supersaturation generation of the nanoplex. To address the poor colloidal stability of conventional nanoplex formulations, we herein developed a new class of CUR nanoplex by complexation of CUR with bovine serum albumin (BSA). The effects of two key variables in drug-protein complexation, i.e. pH and mixing ratio (MBSA/CUR), on the physical characteristics and preparation efficiency were investigated. While the CUR-BSA nanoplex preparation was found to favor acidic pH and MBSA/CUR below unity, the nanoplex's physical characteristics were minimally affected by pH and MBSA/CUR. At the optimal condition, CUR-BSA nanoplex with size ≈90nm, zeta potential ≈27mV, and payload ≈70% were produced at nearly 100% CUR utilization rate and ≈80% yield. The nanoplex produced a prolonged supersaturation level at ≈9× of the saturation solubility for 4h. The dissolution rate could be modulated by thermal treatment of the nanoplex post its preparation. The long-term amorphous state stability, storage colloidal stability, and preserved bioactivity of the nanoplex were successfully established. Lastly, the CUR-BSA nanoplex was found to be superior to the conventional nanoplex in its size, supersaturation generation, colloidal stability, and yield.

Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.

Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (<6%). The maximum achievable payload was equal to ≈2.5µg/cm(2), which was multifold higher than that achieved had inkjet printing of ciprofloxacin solution been performed. Nevertheless, print substrate with higher liquid uptake capacity is needed to increase the payload nearer to the therapeutic dose. Lastly, the drug release and non-cytotoxicity of the printed nanodrug were successfully established in vitro.

Preserving the supersaturation generation capability of amorphous drug-polysaccharide nanoparticle complex after freeze drying.

While the supersaturation generation capability of amorphous nanopharmaceuticals (NPs) in their aqueous suspension form has been well established, their supersaturation generation is adversely affected after drying. Herein we investigated the effects of freeze drying on the supersaturation generation capability of a new class of amorphous NPs referred to as drug nanoplex prepared and stabilized by electrostatic complexation of drug molecules with polysaccharides (dextran sulfate). Using ciprofloxacin as the model drug, two types of freeze-drying adjuvants were investigated, i.e., (1) highly water-soluble excipient (trehalose, mannitol), whose role was to prevent irreversible NPs aggregations upon drying, and (2) crystallization inhibitor (hydroxypropylmethylcellulose (HPMC)), whose role was to suppress crystallization of the dissolved drug and the remaining solid phase. The results showed that dual-adjuvant formulations (i.e. trehalose-HPMC and mannitol-HPMC) were required to preserve the supersaturation generation capability of the drug nanoplex suspension after drying. Freeze drying with only one adjuvant type, or incorporating HPMC as physical mixtures with the freeze-dried nanoplex, were ineffective in preserving the supersaturation. The dual-adjuvant formulations produced prolonged supersaturation levels over 240min at ≈6-8× of the saturation solubility with comparable area under the curve (AUC) in the concentration versus time plot as that exhibited by the suspension form.

Influence of salt type and ionic strength on self-assembly of dextran sulfate-ciprofloxacin nanoplexes.

We evaluated an analytical setup to identify optimal preparation conditions for nanoplex formation of small molecule drugs and polyelectrolytes using ciprofloxacin (CIP) and dextran sulfate (DS) as model compounds. The suitability of isothermal titration calorimetry (ITC) as a screening tool for rational formulation optimization was assessed. Besides ITC, static and dynamic light scattering, zeta potential measurements and scanning electron microscopy were applied to analyze the influence of different salt types and ionic strengths on CIP/DS nanoplex formation. The addition of low amounts of salt, especially 0.1M NaCl, improved the formation of CIP/DS nanoplexes. The presence of low amounts of salt led to smaller and more numerous particles of higher uniformity but had no influence on the release of CIP from nanoplexes. Furthermore, the molar range, within which efficient complexation was achieved, was broader in the presence of 0.1M NaCl than in the absence of salt with overall comparable complexation efficiency. Importantly, binding affinity correlated with particle shape and morphology, potentially enabling optimization of critical quality attributes based on ITC data. Altogether, ITC along with supplemental methods is a versatile screening tool for the evaluation of nanoplex formulation conditions regarding mixing ratio, salt type and ionic strength.

Amorphous nanodrugs prepared by complexation with polysaccharides: carrageenan versus dextran sulfate.

Amorphous nanodrugs prepared by electrostatic complexation of drug molecules with oppositely charged polysaccharides represent a promising bioavailability enhancement strategy for poorly-soluble drugs owed to their high supersaturation generation capability and simple preparation. Using ciprofloxacin (CIP) as the model drug, we investigated the effects of using dextran sulfate (DXT) or carrageenan (CGN) on the (1) preparation efficiency, (2) physical characteristics, (3) supersaturation generation, (4) antimicrobial activity, and (5) cytotoxicity of the amorphous drug-polysaccharide nanoparticle complex (nanoplex) produced. Owing to the higher charge density and chain flexibility of DXT, coupled with the greater hydrophobicity of CGN, the CIP-DXT nanoplex exhibited superior preparation efficiency and larger size than the CIP-CGN nanoplex. Whereas the low solubility and high gelation tendency of CGN resulted in superior supersaturation generation capability for the CIP-DXT nanoplex. The non-cytotoxicity, antimicrobial activity, colloidal, and amorphous state stability were established for both nanoplexes, making them an ideal supersaturated drug delivery system.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified.

Amorphization strategy affects the stability and supersaturation profile of amorphous drug nanoparticles.

Amorphous drug nanoparticles have recently emerged as a promising bioavailability enhancement strategy of poorly soluble drugs attributed to the high supersaturation solubility generated by the amorphous state and fast dissolution afforded by the nanoparticles. Herein we examine the effects of two amorphization strategies in the nanoscale, i.e., (1) molecular mobility restrictions and (2) high energy surface occupation, both by polymer excipient stabilizers, on the (i) morphology, (ii) colloidal stability, (iii) drug loading, (iv) amorphous state stability after three-month storage, and (v) in vitro supersaturation profiles, using itraconazole (ITZ) as the model drug. Drug-polyelectrolyte complexation is employed in the first strategy to prepare amorphous ITZ nanoparticles using dextran sulfate as the polyelectrolyte (ITZ nanoplex), while the second strategy employs pH-shift precipitation using hydroxypropylmethylcellulose as the surface stabilizer (nano-ITZ), with both strategies resulting in >90% ITZ utilization. Both amorphous ITZ nanoparticles share similar morphology (∼300 nm spheres) with the ITZ nanoplex exhibiting better colloidal stability, albeit at lower ITZ loading (65% versus 94%), due to the larger stabilizer amount used. The ITZ nanoplex also exhibits superior amorphous state stability, attributed to the ITZ molecular mobility restriction by electrostatic complexation with dextran sulfate. The higher stability, however, is obtained at the expense of slower supersaturation generation, which is maintained over a prolonged period, compared to the nano-ITZ. The present results signify the importance of selecting the optimal amorphization strategy, in addition to formulating the excipient stabilizers, to produce amorphous drug nanoparticles having the desired characteristics.

Antibiotic polymeric nanoparticles for biofilm-associated infection therapy.

Polymeric nanoparticles are highly attractive as drug delivery vehicles due to their high structural integrity, stability during storage, ease of preparation and functionalization, and controlled release capability. Similarly, lipid-polymer hybrid nanoparticles, which retain the benefits of polymeric nanoparticles plus the enhanced biocompatibility and prolonged circulation time owed to the lipids, have recently emerged as a superior alternative to polymeric nanoparticles. Drug nanoparticle complex prepared by electrostatic interaction of oppositely charged drug and polyelectrolytes represents another type of polymeric nanoparticle. This chapter details the preparation, characterization, and antibiofilm efficacy testing of antibiotic-loaded polymeric and hybrid nanoparticles and antibiotic nanoparticle complex.

Controlled release of Lactobacillus rhamnosus biofilm probiotics from alginate-locust bean gum microcapsules.

Chitosan-coated alginate microcapsules containing high-density biofilm Lactobacillus rhamnosus have been previously shown to exhibit higher freeze drying- and thermal-tolerance than their planktonic counterparts. However, their cell release profile remains poor due to the capsules' susceptibility to the gastric environment. Herein the effects of adding locust bean (LB) and xanthan (XT) gums to alginate (AGN) capsules on the stress tolerance and cell release profiles in simulated gastrointestinal fluids are investigated. Compared to the AGN-only capsules, the AGN-LB capsules exhibit improved stress tolerance (i.e. ≈ 6x for freeze drying, 100x for thermotolerance, 10x for acid), whereas the AGN-XT capsules only improve the acid tolerance. Importantly, the AGN-LB capsules possess the optimal cell release profile with a majority of cells released in the simulated intestinal juice than in the gastric juice. The AGN-LB capsules' superiority is attributed to their stronger interaction with the chitosan coating and high swelling capacity, thus delaying their bulk dissolution.

Biofilm-like Lactobacillus rhamnosus probiotics encapsulated in alginate and carrageenan microcapsules exhibiting enhanced thermotolerance and freeze-drying resistance.

Microcapsules containing high-density biofilm-like Lactobacillus rhamnosus probiotics, in place of planktonic cells, are developed in order to enhance the cell viability upon exposures to stresses commonly encountered during food lifecycle (i.e., heating, freeze-drying, refrigerated storage, and acid). The high-density (HD) capsules are prepared by in situ cultivation of the planktonic cells in the confined space of polysaccharide-based capsules (i.e., chitosan-coated alginate and carrageenan capsules). Compared to their planktonic counterparts, the HD capsules exhibit higher freeze-drying resistance (~40×) and higher thermotolerance upon prolonged wet heat exposures at 60 and 70 °C (~12-8000×), but not at higher temperatures even for short exposures (i.e., 80 and 100 °C). The enhanced viability of the HD capsules, however, is not observed during the refrigerated storage and exposure to the simulated gastric juice. The alginate capsules are superior to carrageenan owed to their better cell release profile in the simulated intestinal juice and storage viability.

Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications. Their preparation strategy has undergone a shift from the conceptually simple two-step method, involving preformed polymeric nanoparticles and lipid vesicles, to the more principally complex, yet easier to perform, one-step method, relying on simultaneous self-assembly of the lipid and polymer, which has resulted in better products and higher production throughput. The scope of LPNs' applications has also been extended beyond single drug delivery for anticancer therapy, to include combinatorial and active targeted drug deliveries, and deliveries of genetic materials, vaccines, and diagnostic imaging agents. This review details the current state of development for the LPNs preparation and applications from which we identify future research works needed to bring the LPNs closer to its clinical realization.

Towards sustainability: new approaches to nano-drug preparation.

The conversion of drugs into drug nanoparticles (nano-drugs) represents a feasible method to enhance bioavailability of otherwise sparingly soluble-drugs. Nano-drugs enhance bioavailability through the improvement of dissolution rate and saturation solubility of drugs, by virtue of their small sizes. Nano-drugs available in the market are usually produced by top-down methods, such as wet milling and high pressure homogenization. These conventional top-down methods, however, suffer from high energy and time requirement, as well as wide and inconsistent nano-drug size distribution. Furthermore, commercially available nano-drugs are predominantly crystalline while amorphous nano-drugs are largely neglected despite their propensity to generate high saturation solubility. In this review, nonconventional methods to prepare crystalline and amorphous nano-drugs are discussed, with the bioavailability enhancing characteristics highlighted. Both top-down and bottom-up methods are covered, finally, a sustainability-based perspective comparing amorphous and crystalline nano-drugs is presented.

Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations.

Green amorphous nanoplex as a new supersaturating drug delivery system.

The nanoscale formulation of amorphous drugs represents a highly viable supersaturating drug-delivery system for enhancing the bioavailability of poorly soluble drugs. Herein we present a new formulation of a nanoscale amorphous drug in the form of a drug-polyelectrolyte nanoparticle complex (or nanoplex), where the nanoplex is held together by the combination of a drug-polyelectrolyte electrostatic interaction and an interdrug hydrophobic interaction. The nanoplex is prepared by a truly simple, green process that involves the ambient mixing of drug and polyelectrolyte (PE) solutions in the presence of salt. Nanoplexes of poorly soluble acidic (i.e., ibuprofen and curcumin) and basic (i.e., ciprofloxacin) drugs are successfully prepared using biocompatible poly(allylamine hydrochloride) and dextran sulfate as the PE, respectively. The roles of salt, drug, and PE in nanoplex formation are examined from ternary phase diagrams of the drug-PE complex, from which the importance of the drug's charge density and hydrophobicity, as well as the PE ionization at different pH values, is recognized. Under the optimal conditions, the three nanoplexes exhibit high drug loadings of ~80-85% owing to the high drug complexation efficiency (~90-96%), which is achieved by keeping the feed charge ratio of the drug to PE below unity (i.e., excess PE). The nanoplex sizes are ~300-500 nm depending on the drug hydrophobicity. The nanoplex powders remain amorphous after 1 month of storage, indicating the high stability owed to the PE's high glass-transition temperature. FT-IR analysis shows that functional groups of the drug are conserved upon complexation. The nanoplexes are capable of generating prolonged supersaturation upon dissolution with precipitation inhibitors. The supersaturation level depends on the saturation solubility of the native drugs, where the lower the saturation solubility, the higher the supersaturation level. The solubility of curcumin as the least-soluble drug is magnified 9-fold upon its transformation to the nanoplex, and the supersaturated condition is maintained for 5 h.

A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles.

Lipid-polymer hybrid nanoparticles - polymeric nanoparticles enveloped by lipid layers - have emerged as a potent therapeutic nano-carrier alternative to liposomes and polymeric nanoparticles. Herein we perform comparative studies of employing spray drying (SD) and spray freeze drying (SFD) to produce inhalable dry-powder form of drug-loaded lipid-polymer hybrid nanoparticles. Poly(lactic-co-glycolic acid), lecithin, and levofloxacin are employed as the polymer, lipid, and drug models, respectively. The hybrid nanoparticles are transformed into micro-scale nanoparticle aggregates (or nano-aggregates) via SD and SFD, where the effects of (1) different excipients (i.e. mannitol, polyvinyl alcohol (PVA), and leucine), and (2) nanoparticle to excipient ratio on nano-aggregate characteristics (e.g. size, flowability, aqueous reconstitution, aerosolization efficiency) are examined. In both methods, PVA is found more effective than mannitol for aqueous reconstitution, whereas hydrophobic leucineis needed to achieve effective aerosolization as it reduces nano-aggregate agglomeration. Using PVA, both methods are equally capable of producing nano-aggregates having size, density, flowability, yield and reconstitutibility in the range ideal for inhaled delivery. Nevertheless, nano-aggregates produced by SFD are superior to SD in terms of their aerosolization efficiency manifested in the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter.

Self-assembled amorphous drug-polyelectrolyte nanoparticle complex with enhanced dissolution rate and saturation solubility.

The dissolution rate and solubility of poorly soluble drugs can be enhanced by formulating them into stable amorphous nanoparticle complex (nanoplex). For this purpose, a highly sustainable self-assembly drug-polyelectrolyte complexation process is developed, with ciprofloxacin and dextran sulfate as the drug and polyelectrolyte models, respectively. The nanoplex are prepared by mixing two aqueous salt solutions - one containing the drug and the other containing the oppositely charged polyelectrolyte. The nanoplex suspension is transformed into stable dry-powder form by freeze-drying. The effects of drug concentration, drug-to-polyelectrolyte charge ratio, and salt concentration on the complexation efficiency, yield, drug loading, and nanoplex morphology are examined. The dissolution rates and solubility of the nanoplex are characterized and compared to raw drug crystals. Nearly spherical amorphous nanoplex having fairly uniform sizes in the range of 200-400 nm and 80% drug loading are successfully produced at ≥80% complexation efficiency and yield. The complexation efficiency is governed by the drug concentration and its ratio to the salt concentration. The nanoplex powders exhibit approximately twice higher dissolution rate and solubility than raw drug crystals and remain stable after one-month storage. Overall, amorphous nanoplex represent a promising bioavailability-enhanced formulation of poorly soluble drugs owed to their superior characteristics and ease of preparation.

Green preparation of antibiotic nanoparticle complex as potential anti-biofilm therapeutics via self-assembly amphiphile-polyelectrolyte complexation with dextran sulfate.

Nanoscale antibiotic delivery has emerged as a promising therapeutic means to treat lung biofilm infection owed to its sputum penetrating ability. Due to the high antibiotic dosage requirement in anti-biofilm therapy, the most suitable formulation for this purpose is the antibiotic nanoparticles themselves, instead of the more extensively studied antibiotic-loaded nano-carriers, which often exhibit low drug loading. The present work details the preparation and characterization of antibiotic nanoparticle complex (or nanoplex) by self-assembly amphiphile-polyelectrolyte complexation process. Ofloxacin (OFX) and levofloxacin (LEV) are used as the antibiotics with dextran sulfate (DXT) as the polyelectrolyte. The nanoplex possesses high drug loading (up to 80%) and size<400nm ideal for sputum penetration. Unlike existing methods to prepare drug nanoparticles, the present method is fast, energy-minimal, solvent-free, and highly efficient as manifested in nearly 100% of drug is transformed into nanoplex. The effects of drug-to-polyelectrolyte charge ratio, pH, drug, and salt concentrations on the nanoplex characteristics (i.e. size, stability, drug loading) are investigated from which the optimal preparation conditions have been identified. Higher complexation efficiency and stronger agglomeration tendency are observed for LEV nanoplex owed to its higher hydrophobicity. The antibiotics are completely released from the nanoplex in aqueous salt solution within 3h and their antimicrobial activity is preserved upon complexation. The nanoplex is readily transformed into amorphous dry powders that remain stable after one-month storage owed to the high glass transition temperature. The antibiotic nanoplexes are highly charged enabling their subsequent functionalization for targeted delivery and controlled drug release purposes.