Drug Delivery Kinetics Research Articles

Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods.

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.

DNA-Scaffolded Disulfide Redox Network for Programming Drug-Delivery Kinetics.

In response to specific stimuli, dynamic covalent materials enable the generation of new structures by reversibly forming/breaking chemical bonds, thus showing great potential for application in controlled drug release. However, using dynamic covalent chemistry to program drug-delivery kinetics remains challenging. Herein, an in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported in which nucleic acids are used as a scaffold for dynamic disulfide bonds. The constructed DdiSRN allows selective release of loading cargos inside cancer cells in response to redox stimuli. Moreover, the density of disulfide bonds in network can be tuned by precise control over their position and number on DNA scaffolds. As a result, drug-delivery kinetics can be programmed with a half-life, t1/2 , decreasing from 8.3 to 4.4 h, thus facilitating keeping an adequate drug concentration within the therapeutic window. Both in vitro and in vivo studies confirm that co-delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN enhances the therapeutic effect on multidrug-resistant cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.

Assessment of Drug Delivery Kinetics to Epidermal Targets In Vivo

It has proven challenging to quantify ‘drug input’ from a formulation to the viable skin because the epidermal and dermal targets of topically applied drugs are difficult, if not impossible, to access in vivo. Defining the drug input function to the viable skin with a straightforward and practical experimental approach would enable a key component of dermal pharmacokinetics to be characterised. It has been hypothesised that measuring drug uptake into and clearance from the stratum corneum (SC) by tape-stripping allows estimation of a topical drug’s input function into the viable tissue. This study aimed to test this idea by determining the input of nicotine and lidocaine into the viable skin, following the application of commercialised transdermal patches to healthy human volunteers. The known input rates of these delivery systems were used to validate and assess the results from the tape-stripping protocol. The drug input rates from in vivo tape-stripping agreed well with the claimed delivery rates of the patches. The experimental approach was then used to determine the input of lidocaine from a marketed cream, a typical topical product for which the amount of drug absorbed has not been well-characterised. A significantly higher delivery of lidocaine from the cream than from the patch was found. The different input rates between drugs and formulations in vivo were confirmed qualitatively and quantitatively in vitro in conventional diffusion cells using dermatomed abdominal pig skin.

Effect of continuous and multi-phasic current profiles on the iontophoretic transport of pramipexole, rasagiline and huperzine A: Depicting temporal variation and biodistribution in the skin

Transdermal iontophoresis is an interesting option for the non-invasive controlled delivery of therapeutic agents to treat neurodegenerative diseases. The current profile controls drug delivery kinetics and enables complex drug input profiles to be obtained. The aim of this study was to investigate the temporal variation in transport of pramipexole (PRA), rasagiline (RAS) and huperzine A (HUP) using continuous and multi-phasic current profiles by measuring cumulative permeation, transdermal flux and drug retention in the skin upon modulation of the applied current profile during a single experiment in vitro. Initial experiments with continuous current were conducted to establish a correlation between total delivery of PRA, RAS and HUP (i.e. sum of the cumulative permeation and skin deposition) and the amount of charge transferred. Subsequent experiments with multi-phasic current profiles, confirmed that the relationship between amounts of charge transferred and total delivery was able to predict the total delivery of each drug. Experimental values were within ± 15% of the predicted values. Current density and duration of current application were also shown to have a significant impact on the skin biodistribution of PRA. These results also provide insight into the rate of formation of iontophoretic drug reservoirs in the skin.

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

Some cancers such as human breast cancer, prostate cancer, and lung cancer easily metastasize to bone, leading to osteolysis and bone destruction accompanied by a complicated microenvironment. Systemic administration of bisphosphonates (BP) or denosumab is the routine therapy for osteolysis but with non-negligible side effects such as mandibular osteonecrosis and hypocalcemia. Thus, it is imperative to exploit optimized drug delivery systems, and some novel nanotechnology and nanomaterials have opened new horizons for scientists. Targeted and local drug delivery systems can optimize biodistribution depending on nanoparticles (NPs) or microspheres (MS) and implantable biomaterials with the controllable property. Drug delivery kinetics can be optimized by smart and sustained/local drug delivery systems for responsive delivery and sustained delivery. These delicately fabricated drug delivery systems with special matrix, structure, morphology, and modification can minimize unexpected toxicity caused by systemic delivery and achieve desired effects through integrating multiple drugs or multiple functions. This review summarized recent studies about optimized drug delivery systems for the treatment of cancer metastatic osteolysis, aimed at giving some inspiration in designing efficient multifunctional drug delivery systems.

Effect of poly lactic-co-glycolic acid encapsulation on drug delivery kinetics from vancomycin-impregnated Ca-Mg silicate scaffolds

The identification of drug delivery mechanisms is critical to design a device that offers a drug release kinetics within the therapeutic window. In this paper, the drug release kinetics of bioresorbable tissue engineering scaffolds coated/uncoated with biodegradable polymer layers is studied. Interconnectedly porous bredigite (MgCa7Si4O16) scaffolds were fabricated by a sacrificial urethane foam replica method, loaded with vancomycin hydrochloride (C66H75Cl2N9O24) and then encapsulated in poly lactic-co-glycolic acid (PLGA, LA/GA = 50:50) coatings of two different thicknesses. Field-emission scanning electron microscopy (FESEM) and Fourier-transform infrared spectroscopy (FTIR) were used to verify the macroporous morphology and chemical constituents of the devices. The release profiles of vancomycin from these systems into phosphate buffered saline (PBS) at 37 °C were also recorded by ultraviolet-visible (UV–vis) spectroscopy. To explore the dominant drug delivery mechanisms, the experimental data of the drug release was then fitted with several drug delivery mathematical models, including the Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Peppas-Sahlin, Weibull, zero-order and first-order. Comparing the correlation coefficient of the regressions as a measure of goodness-of-fit, it was found that vancomycin release from the bare scaffold is subjected to a dissolution-controlled kinetics, whereas the PLGA-coated scaffolds mainly display a combination of diffusion- and dissolution-controlled mechanisms for the drug release. It can be accordingly concluded that the bredigite scaffolds are a versatile device for different local drug delivery strategies offering rapid, single-stage and dissolution-controlled release kinetics that can be easily modulated into a diffusion-controlled, biphasic and prolonged release through biopolymer coating.

Drug-delivery Ca-Mg silicate scaffolds encapsulated in PLGA.

The aim of this work is to develop dual-functional scaffolds for bone tissue regeneration and local antibiotic delivery applications. In this respect, bioresorbable bredigite (Ca7MgSi4O16) porous scaffolds were fabricated by a foam replica method, loaded with vancomycin hydrochloride and encapsulated in poly lactic-co-glycolic acid (PLGA) coatings. Field emission scanning electron microscopy, Archimedes porosimetry and Fourier-transform infrared spectroscopy were used to characterize the structure of the scaffolds. The drug delivery kinetics and cytocompatibility of the prepared scaffolds were also studied in vitro. The bare sample exhibited a burst release of vancomycin and low biocompatibility with respect to dental pulp stem cells based on the MTT assay due to the fast bioresorption of bredigite. While keeping the desirable characteristics of pores for tissue engineering, the biodegradable PLGA coatings modified the drug release kinetics, buffered physiological pH and hence improved the cell viability of the vancomycin-loaded scaffolds considerably.

Air-jet spinning corn zein protein nanofibers for drug delivery: Effect of biomaterial structure and shape on release properties.

Nanofiber materials are commonly used as delivery vehicles for dermatological drugs due to their high surface-area-to-volume ratio, porosity, flexibility, and reproducibility. In this study air-jet spinning was used as a novel and economic method to fabricate corn zein nanofiber meshes with model drugs of varying solubility, molecular weight and charge. The release profiles of these drugs were compared to their release from corn zein films to elucidate the effect of geometry and structure on drug delivery kinetics. In film samples, over 50% of drug was released after only 2h. However, fiber samples exhibited more sustained release, releasing less than 50% after one day. FTIR, SEM, and DSC were performed on nanofibers and films before and after release of the drugs. Structural analysis revealed that the incorporation of model drugs into the fibers would transform the zein proteins from a random coil network to a more alpha helical structure. Upon release, the protein fiber reverted to its original random coil network. In addition, thermal analysis indicated that fibers can protect the drug molecules in high temperature above 160°C, while drugs within films will degrade below 130°C. These findings can likely be attributed to the mechanical infiltration of the drug molecules into the ordered structure of the zein fibers during their solution fabrication. The slow release from fiber samples can be attributed to this biophysical interaction, illustrating that release is dictated by more than diffusion in protein-based carriers. The controlled release of a wide variety of drugs from the air-jet spun corn zein nanofiber meshes demonstrates their success as drug delivery vehicles that can potentially be incorporated into different biological materials in the future.

Competition of carrier bioresorption and drug release kinetics of vancomycin-loaded silicate macroporous microspheres to determine cell biocompatibility

Bioceramic porous microspheres are promising substances for dental and orthopedic bone void filling, tissue engineering and drug delivery applications. In this research, the structure and cytocompatibility of bioactive magnesium-calcium silicate macroporous microspheres loaded with vancomycin hydrochloride, an antibiotic drug, were studied. In this regard, bredigite (Ca7MgSi4O16), akermanite (Ca2MgSi2O7) and diopside (CaMgSi2O6) carriers were fabricated through a sequence of sol-gel, calcination, droplet extrusion and sintering processes, followed by impregnated with vancomycin. X-ray diffraction (XRD) and scanning electron microscopy verified the formation of the desired ceramic crystalline phases and macroporous characteristics of the carriers, respectively. Based on the MTT assay, the antibiotic-loaded bredigite, akermanite and diopside devices comparatively exhibited the lowest, intermediate and highest levels of human bone marrow mesenchymal stem cells (hBM-MSCs) viability and proliferation, respectively. It was concluded that the role of the carrier bioresorption kinetics prevails over the drug delivery kinetics in determining the cell biocompatibility of the devices.

Computer Modeling of Drug Delivery with Thermosensitive Liposomes in a Realistic Three-Dimensional Geometry.

Thermosensitive liposomes (TSL) are nanoparticles that can encapsulate therapeutic drugs, and release those drugs when exposed to hyperthermic temperatures (>40 °C). Combined with localized hyperthermia, TSL enable focused drug delivery. In this study, we created a three-dimensional (3D) computer model for simulating delivery with TSL-encapsulated doxorubicin (TSL-Dox) to mouse tumors. A mouse hind limb was scanned by a 3D scanner and the resulting geometry was imported into finite element modeling software, with a virtual tumor added. Then, heating by a surface probe was simulated. Further, a drug delivery model was coupled to the heat transfer model to simulate drug delivery kinetics. For comparison, experimental studies in gel phantoms and in vivo fluorescence imaging studies in mice carrying lung tumor xenografts were performed. We report the tissue temperature profile, drug concentration profile and compare the experimental studies with the computer model. The thermistor produced very localized heating that resulted in highest drug delivery to regions near the probe. The average tumor temperature was 38.2˚C (range 34.4-43.4˚C), and produced an average tumor drug concentration of 11.8 µg/g (0.3-28.1 µg/g) after 15 min heating, and 25.6 µg/g (0.3-52 µg/g), after 60 min heating. The computer model reproduced the temperature profile compared to phantom experiments (mean error 0.71 °C, range 0.59-1.25 °C), as well as drug delivery profile as compared to in vivo studies. Our results suggest feasibility of using this approach to model drug delivery in preclinical studies with accurate model geometry.

BCS class II drug loaded protein nanoparticles with enhanced oral bioavailability: in vitro evaluation and in vivo pharmacokinetic study in rats

The aim of the study was to improve the bioavailability of atorvastatin calcium (ATC) by formulating polymeric nanoparticles (NPs) with an easy and cost-effective approach. ATC entrapped gelatin nanoparticles (AEGNPs) were prepared by using a simple one-step desolvation method. The formed NPs were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Morphological study exhibited a homogenous spherical shape of formulated NPs. FTIR studies revealed the chemical compatibility of the drug with gelatin. The improvement in drug delivery kinetics of AEGNPs could be attributed to amorphization along with the reduction in particle size of ATC. The pharmacokinetic study in Sprague-Dawley rats revealed that the Cmax and AUC0–24 of AEGNPs in rats were ∼4-fold and ∼11-fold higher than that of pure ATC suspension. The research presented successfully shows that AEGNPs preparation by one-step desolvation, using minimum excipients is a quick, easy and reproducible method. These results suggest that the ATC encapsulated gelatin NP is a promising approach for the oral delivery of ATC, improving the bioavailability of the drug.

Cyclodextrin and cellulose combination product developed by click chemistry: fascinating design for inclusion of ciprofloxacin

In the current study, we introduce “click chemistry” as a powerful tool to tailor cyclodextrin–cellulose combination product followed by the inclusion of ciprofloxacin hydrochloride (CipHCl) as antibacterial agent. Initially, beta-cyclodextrin (β-CD) and cellulose fibers (CFs) were modified so as to be mono-6-propargylamino-6-deoxy-β-CD (Pro-β-CD) and azidated cellulose fibers (CFs-N3), respectively. Afterward, the “click reaction” was carried out between Pro-β-CD and CFs-N3 to fabricate a covalent grafting of β-CD onto CFs resulting in click product (CFs-N3@Pro-β-CD). The drug-delivery kinetics of the loaded CipHCl was performed by immersing samples into an aqueous solution, and the amount of adsorbed and released CipHCl was measured, as a function of time, by UV spectroscopy. Compared to original CFs, the load quantity of CipHCl into the click product was greatly increased, the release time of CipHCl from CFs-N3@Pro-β-CD was prolonged, and considerably higher antibacterial activity against E. coli and S. aureus was observed. The click product exhibited excellent antibacterial activity and sustained antibacterial efficacy up to 12 and 10 days against S. aureus and E. coli. The results showed that β-CD has been successfully grafted onto CFs via covalent bonds, while maintaining the intrinsic properties and the integrity of the fibers. Compared with the control paper sheet, the mechanical properties of the paper are well preserved.

BEPO®: Bioresorbable diblock mPEG-PDLLA and triblock PDLLA-PEG-PDLLA based in situ forming depots with flexible drug delivery kinetics modulation

This article presents BEPO®, an in situ forming depot (ISFD) technology mediated by a solvent-exchange mechanism. The matrix of the in situ formed drug delivery depot is composed of the combination of a diblock (DB) and a triblock (TB) polyethylene glycol-polyester copolymer. This combination offers a broad capability to tune the release of a wide variety of drugs to the desired pharmacokinetics. The work described in the present article demonstrates that the delivery rate and profile can be adjusted by changing the composition of either TB or DB or the relative ratio between them, among other parameters. It has been shown that the polymeric composition of the formulation has a substantial impact on the solvent exchange rate between the organic solvent and the surrounding aqueous medium which subsequently determines the internal structure of the resulting depot and the delivery of the therapeutic cargo. This has been demonstrated studying the in vitro release of two model molecules: bupivacaine and ivermectin.Formulations releasing these drugs have been administered to animal models to show the possibility of delivering therapeutics from weeks to months by using BEPO® technology.

Light-, temperature-, and pH-responsive micellar assemblies of spiropyran-initiated amphiphilic block copolymers: Kinetics of photochromism, responsiveness, and smart drug delivery.

Multi-responsive polymer assemblies are a significant class of smart polymers with potential applications in drug-delivery and gen-delivery systems. Poly(dimethylaminoethyl methacrylate) (PDMAEMA) is among the most applicable multi-responsive polymers that changes its physical and chemical properties in response to temperature, pH, and CO2. Herein, different types of light-, temperature-, pH-, and CO2-responsive polymer assemblies were developed based on multi-responsive PDMAEMA and hydrophobic poly(methyl methacrylate) blocks. In addition, spiropyran was incorporated at the chain ends by using spiropyran-initiated atom transfer radical polymerization method. Novel smart drug-delivery systems were developed by self-assembly of these amphiphilic block copolymers to micellar morphologies in aqueous media. Dynamic light scattering results showed that size of the polymer assemblies changed in response to pH variations (from 5 to 9), temperature changes (above the lower critical solution temperature (LCST) of PDMAEMA), and also UV light irradiation (wavelength of 365nm). The LCST of PPDMAEMA showed a shift from 53 to 60°C after isomerization of the SP to MC form, as a result of increase of polarity and water-solubility. The PDMAEMA block results in responsivity of the prepared copolymer assemblies to CO2, which display pH variation from 8-8.6 to 5-6 after 2min of CO2 gas bubbling. All the multi-responsive micellar polymer assemblies showed various loading capacities and release profiles, and the DOX release can be controlled by pH, temperature, and light. The release efficiency is reached to 60-85% at pH5.3, 80-90% at temperatures higher than the LCST of PDMAEMA (60°C), and also 90-100% under UV light irradiation after 48h. In summary, the multi-responsive polymer assemblies based on amphiphilic block copolymers containing spiropyran chain end groups in the current study have potential applications in smart drug-delivery systems, and offer controlling over the drug-release by different triggers, such as light irradiation, pH variation, and temperature change. A very low concentration of spiropyran molecules (one per polymer chain) showed light-controlling of drug-release from the assemblies with high efficiencies.

The role of cellulose nanocrystals in biocompatible starch-based clicked nanocomposite hydrogels

Starch-based nanocomposite hydrogels were successfully prepared by the Diels-Alder click cross-linking reaction between furan-functionalized starch derivative and a water-soluble tetrafunctional maleimide compound, adding cellulose nanocrystals (CNC) as nanoreinforcement. The effect of increasing the CNC content on rheological and swelling properties as well as on the morphology of the hydrogels was analyzed. Besides, in order to evaluate the applicability of the as-prepared hydrogels as delivery systems, drug release measurements and in vitro cytotoxicity assays were also performed. It was found that the prepared nanocomposite hydrogels presented higher stiffness as the CNC content increased. The incorporation of the nanocrystals modified the internal porous microstructure of the hydrogels, affecting consequently both the swelling capacity and the drug-delivery kinetics. Moreover, the prepared nanocomposite hydrogels showed non-toxic behavior, demonstrating their potential applicability in the biomedical field, especially as sustained drug delivery systems.

Programming Drug Delivery Kinetics for Active Burst Release with DNA Toehold Switches.

Despite smart drug delivery systems (DDSs) with high delivery efficiency and improved efficacy for chemotherapy, precise drug release in targeted tumor cells in a controllable way is still challenging. In this work, we develop DNA toehold switch-engineered spherical nucleic acid-templated hydrogel (SNAgel) for on-site active burst release of chemotherapeutic (tumor-killing) drugs in target cancer cells. By designing ligand-specific toehold sequences on hybridization chain reaction (HCR)-generated SNAgel, we realize burst release of payloads with a wide range of t1/2 ranging from 60.52 to 5.49 min by active dynamic control of the kinetics. The camouflage of SNAgels with compact DNA shell enables elongated/prolonged blood circulation and targeted accumulation, cell entry, and apoptosis induction in vivo. The enhanced anticancer activity of SNAgels was substantiated in both cancer cell lines and xenografted tumor-bearing mice. This DNA-engineered kinetic control approach sheds new light on developing paradigm-shifting DDSs for cancer therapeutics.

Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin.

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds.

Swelling and drug delivery kinetics of click-synthesized hydrogels based on various combinations of PEG and star-shaped PCL: influence of network parameters on swelling and release behavior

Polyethylene glycol (PEG)- and polyethylene glycol–polycaprolactone (PEG–PCL)-based hydrogels were synthesized with various compositions of prepolymers by using ROP and click chemistry methods. Relevant prepolymers were characterized by 1H NMR and FTIR spectroscopy. In order to study the influence of network parameters on swelling and release kinetics, experimental data were approximated by several mathematical models including zero order, first order, Higuchi and Korsmeyer–Peppas to determine the kinetics of swelling and diclofenac sodium release from hydrogels. The obtained results showed that the swelling and release data were best fitted to Korsmeyer–Peppas model. The results of the swelling study showed that the swelling properties of the hydrogels varied with the changes in the PEG molecular weights, as well as concentration of PCL. All of the hydrogels showed non-Fickian diffusion, but when PCL concentration increased and PEG molecular weights decreased, the n values were decreased and reached n = 0.5 (Fickian diffusion). The kinetics of diclofenac sodium release from hydrogels showed similar behavior so that in F hydrogels with the highest PCL concentration, the release mechanism fully changed from non-Fickian to Fickian diffusion. In other words, with increasing cross-link density and PCL concentration, the swelling degree and flexibility of networks decreased. Therefore, the swelling and release mechanism changed from non-Fickian to Fickian diffusion.

PEGylation influences drug delivery from nanogels

PEGylation is an industrial commonly used approach for improving the biodistribution of drugs and biomolecules within the human body. Indeed it helps to improve systemic circulation time and decreases immunogenicity. While the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has been widely studied, their role in modifying drug delivery, to the best of our knowledge, has never been addressed directly. Here we studied the influence of different PEGylation strategies in colloids drug loading and then on mass transport performances (i.e. drug delivery kinetics). Coatings were prepared using PEG monomethyl ether (mPEG), modifying its terminal hydroxyl groups with different linkers: imidazole and carboxyl terminal groups. Mass transport experiments showed that taking advantage of drug-polymer interactions it is possible to tune drug loading within colloids and their consequent release. This outcome could be considered a promising perspective of nanogels use as carriers for drug delivery, improving their therapeutic effect through polymer surface modifications.

Using Nanoparticle Drug Delivery Mechanisms to Improve Eye Moisture Over Extended Periods of Contact Lens Wear

Millions of people around the world suffer from dry eye symptoms as a result of extended contact lens wear. The objective of this design document is to engineer a solution for chronic dry eyes. The solution must be safe, effective, easy to use, and affordable. The goal of the treatment is to decrease tear film osmolarity by 20 mOsmol/L. Three types of nanotechnologies were considered for this task. The candidate solutions were 1) hydrogel contact lenses infused with lubricant-loaded liposomes, 2) lubricant-loaded microemulsions applied as eye drops, and 3) lubricant-loaded niosomes applied as eye drops. All solutions use polyethylene glycol 400 as the primary active ingredient in the lubricant. The three solutions provide a safe treatment option that allows increased bioavailability of drug and increased retention time, as well as controlled release of drug. A combination of candidates 1 and 3 – namely, hydrogel contact lenses infused with lubricant-loaded niosomes – seems to be the best solution because of excellent drug delivery kinetics and minimal safety concerns. The success of this project would encourage further research in niosome-based and contact lens-based drug delivery. It would also allow this company to expand research and development and further specialize in ocular drug delivery.