Sustainable Aquafeed Formulations Containing Insect Larval Meal and Grape Marc for the New Zealand Farmed Abalone.

The aquaculture industry has been criticised for the excessive use of fish meal (FM) in feeds due to the utilisation of wild fish in the formulation and the exacerbation of overfishing marine resources. Land-based abalone aquaculture mainly uses commercial feeds (CFs) to promote faster growth, which include FM as a primary protein component. Alternative ingredients, such as insect meal (IM) and grape marc (GM) are potential candidates for FM replacement due to their suitable nutritional profile and sustainable production. This paper reports on a novel nutritional approach for the New Zealand farmed abalone, which replaces FM with IM by 10% and includes a waste by-product (GM) by 30% as a potential prebiotic source. The study was performed in two stages: (a) physico-chemical determination of diets delivered in an alginate matrix (experimental diets) and their stability in seawater compared to CF and (b) evaluation of growth and feed intake for the New Zealand black-foot abalone. There were significant differences between experimental diets and CF in terms of sinking rate, particle weight, and microscopic observations. Water stability of the experimental diets was increased by 50% in 24 and 48 hr compared to CF, producing less solid waste, and potentially reducing cleaning efforts in the farm. The inclusion of IM and GM did not compromise overall animal growth or their feed conversion ratio, however, further evaluation need to be explored in the future research. The findings revealed that the developed encapsulated feeds are a more stable food delivery method for Haliotis iris compared to the CF. Furthermore, both IM and GM can be included in feed formulations as a more sustainable strategy without compromising weight and shell gains in the abalone farming.

Effect of Dietary Insect Meal and Grape Marc Inclusion on Flavor Volatile Compounds and Shell Color of Juvenile Abalone Haliotis iris.

Almost 60% of the fish meal produced globally is used in aquaculture feeds. Fish meal production relies on finite wild-marine resources and is considered as an unsustainable ingredient. Insect meal (IM) is considered a sustainable source with high levels of protein suitable for growth promotion. Grape marc (GM) is a waste byproduct of the winery industry rich in pigments with antioxidant capacity. However, the inclusion of both ingredients can affect the flavor of the meat of abalone and the color of the shell due to different nutritional profiles. The aim of this study was to evaluate the effect of the dietary inclusion of IM and GM on the flavor volatile compounds and shell color of the juvenile Haliotis iris in a 165-days feeding trial. Abalone were offered four experimental diets with different levels of IM and GM inclusion and a commercial diet (no IM or GM). Soft bodies of abalone were used to characterize volatile compounds using solid-phase microextraction gas chromatography-mass spectrometry, and color changes were analyzed in ground powder of abalone shells using color spectrophotometry 400-700 nm (visible). The results showed 18 volatile compounds significantly different among the dietary treatments. The inclusion of IM did not significantly affect the flavor volatile compounds detected, whereas the inclusion of GM reduced volatile compounds associated with lipid-peroxidation in abalone meat. The inclusion of IM and GM did not significantly affect the lightness nor the yellowness, blueness, redness, and greenness of the ground shells. The supplementation of abalone feeds with GM can help to reduce off-flavour compounds which may extend shelf-life of raw abalone meat.

Enzymatic Crosslinked Hydrogels of Gelatin and Poly (Vinyl Alcohol) Loaded with Probiotic Bacteria as Oral Delivery System.

Probiotic bacteria are widely used to prepare pharmaceutical products and functional foods because they promote and sustain health. Nonetheless, probiotic viability is prone to decrease under gastrointestinal conditions. In this investigation, Lactiplantibacillus plantarum spp. CM-CNRG TB98 was entrapped in a gelatin−poly (vinyl alcohol) (Gel−PVA) hydrogel which was prepared by a "green" route using microbial transglutaminase (mTGase), which acts as a crosslinking agent. The hydrogel was fully characterized and its ability to entrap and protect L. plantarum from the lyophilization process and under simulated gastric and intestine conditions was explored. The Gel−PVA hydrogel showed a high probiotic loading efficiency (>90%) and survivability from the lyophilization process (91%) of the total bacteria entrapped. Under gastric conditions, no disintegration of the hydrogel was observed, keeping L. plantarum protected with a survival rate of >94%. While in the intestinal fluid the hydrogel is completely dissolved, helping to release probiotics. A Gel−PVA hydrogel is suitable for a probiotic oral administration system due to its physicochemical properties, lack of cytotoxicity, and the protection it offers L. plantarum under gastric conditions.

An estriol-eluting pessary to treat pelvic organ prolapse.

Pelvic organ prolapse affects up to 50% of parous women. Commonly used treatment options have unwelcome attributes; pessaries can cause erosion and estrogen creams need to be applied frequently, which is inconvenient and difficult to administer. This study involved the development of an estriol-releasing pessary utilising 3D printing molds. We incorporated varying amounts of estriol (1%, 10% and 15%) into the silicone pessary. We optimised the mechanical aspects of the pessary so it had a similar strength to commercially available pessaries. We investigated estriol release from the pessary over 3 months. We explored possible interactions between the drug and polymers via FTIR. The MED-4870 silicone ring with similar mechanical strength to pessaries currently used to treat pelvic organ prolapse. The medical pessaries present a sustained release in simulated vaginal fluid over 3 months. The pessary with 10% estriol delivered the optimal dose at 0.8 mg each week. Mechanical strength of this pessary showed no difference after emersion in simulated vaginal fluid for 3-month, supporting the long-term application. An estriol-loaded pessary was successfully developed to treat pelvic organ prolapse with sustained release of estriol over 3 months. This pessary provides promising potential to treat pelvic organ prolapse and vaginal atrophy.

3D-Printed Hybrid Collagen/GelMA Hydrogels for Tissue Engineering Applications.

Bioprinting is an emerging technology involved in the fabrication of three-dimensional tissue constructs for the repair and regeneration of various tissues and organs. Collagen, a natural protein found abundantly in the extracellular matrix of several tissues, can be extracted from collagen-rich tissues of animals such as sheep, cows, rats, pigs, horses, birds, and marine animals. However, due to the poor printability of collagen bioinks, biocompatible collagen scaffolds that mimic the extracellular matrix (ECM) are difficult to fabricate using bioprinting techniques. Gelatin methacrylate (GelMA), a semi-synthetic polymer with tunable physical and chemical properties, has been found to be a promising biomaterial in various bioprinting applications. The printability of collagen can be improved by combining it with semi-synthetic polymers such as GelMA to develop hybrid hydrogels. Such hybrid hydrogels printed have also been identified to have enhanced mechanical properties. Hybrid GelMA meshes have not previously been prepared with collagen from ovine sources. This study provides a novel comparison between the properties of hybrid meshes with ovine skin and bovine hide collagen. GelMA (8% w/v) was integrated with three different concentrations (0.5%, 1%, and 2%) of bovine and ovine collagen forming hybrid hydrogels inks that were printed into meshes with enhanced properties. The maximum percentage of collagen suitable for integration with GelMA, forming hybrid hydrogels with a stable degradation rate was 1%. The water-soluble nature of ovine collagen promoted faster degradation of the hybrid meshes, although the structural crosslinking was identified to be higher than bovine hybrid meshes. The 1% bovine collagen hybrid meshes stood out in terms of their stable degradation rates.

Preparation and Characterisation of a Cyclodextrin-Complexed Manuka Honey Microemulsion for Eyelid Application.

Honey has been widely purported as a natural remedy due to its antimicrobial and anti-inflammatory effects. In recent years, several studies have suggested that the considerably high methylglyoxal (MGO) concentration in Manuka honey (MH) makes it particularly effective to manage bacterial overload, such as that observed in blepharitis. However, the poor solubility, high viscosity, and osmolarity of aqueous honey solutions, especially at the high MGO concentrations studied in the literature, render the formulation of an acceptable dosage form for topical application to the eyelids challenging. Here, the antibacterial properties of raw MH and alpha-cyclodextrin (α-CD)-complexed MH were evaluated at relatively low MGO concentrations, and a liquid crystalline-forming microemulsion containing α-CD-complexed MH was formulated. After determining pH and osmolarity, ocular tolerability was assessed using human primary corneal epithelial cells and chorioallantoic membranes, while the antibacterial efficacy was further evaluated in vitro. The α-CD-MH complex had significantly greater antibacterial activity against Staphylococcus aureus than either constituent alone, which was evident even when formulated as a microemulsion. Moreover, the final formulation had a physiologically acceptable pH and osmolarity for eyelid application and was well-tolerated when diluted 1:10 with artificial tear fluid, as expected to be the case after accidental exposure to the ocular surface in the clinical setting. Thus, a safe and efficient MH dosage form was developed for topical application to the eyelids, which can potentially be used to support optimal eyelid health in the management of blepharitis.

Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems.

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

Medicinal cannabis pharmacokinetics and potential methods of delivery.

The evidence of cannabis exhibiting polypharmacological properties has been accumulating for the past few decades, particularly for its analgesic and anti-inflammatory abilities. However, inconsistent dosage forms and erratic absorption levels prevent medicinal cannabis products from becoming mainstream recommendations for pain management. Current cannabis products fail to address the undesirable characteristics associated with cannabinoids such as low solubility, poor bioavailability, and lack of specificity, all of which contribute to low therapeutic effect. In this narrative view, the pharmacokinetics of cannabis products and possible methods of drug delivery, in the form of carrier systems, will be explored. The incorporation of cannabinoids into carrier systems provides an opportunity to improve absorption levels, increase bioavailability and reduce adverse events allowing for a greater therapeutic effect.

Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants.

Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS.

Processing and extraction methods of medicinal cannabis: a narrative review.

INTRODUCTION: As the cannabis industry transitions from a black market to a legal market, product development, and methods of extraction have become a focal point. To date, more than thousands of chemical constituents have been identified from the cannabis plant, all of which possess different chemical properties that require different conditions for preservation during drying and extraction. However, scientific publications that explore these areas for the cannabis plant are currently lacking. METHOD: This is a narrative review paper which focuses on critiquing drying and extraction methods of Cannabis sativa L. plant. Relevant keywords such as medicinal cannabis, extraction, solvent, cannabinoids, and terpenes have been searched in PubMed, EMBASE, MEDLINE, Google Scholar, and Cochrane Library (Wiley) databases. RESULT: To find relevant papers for this narrative review, 93 papers have been reviewed. Among them, 12 irrelevant papers were discarded. The excluded papers were either about hemp seed oil or hemp fiber and protein. Based on this review, solvent extraction is the most common method for cannabis plants. Although solventless and hydrodynamic extraction are known for their high yield and feasibility, more investigation is needed in these areas. Regarding the drying process, hang-drying is the most convenient method; however, it may be substituted by freeze-drying in the near future. DISCUSSION: This review analyses various drying and extraction processes to guide the selection of suitable methods for various types of cannabis products and applications. This is done by outlining traditional and modern methods of drying techniques, exploring the importance of solvents for extraction, visiting solventless extraction procedures, and finally comparing conventional and alternative methods of extraction. CONCLUSION: In conclusion, based on the current knowledge, using organic solvents is the most convenient method for medicinal cannabis extraction. However, more research is needed for some of the drying and extraction methods. Also, developing a green and sustainable cannabis extraction method should be considered for future studies.

Gelatine-based drug-eluting bandage contact lenses: Effect of PEGDA concentration and manufacturing technique.

Drug-eluting bandage contact lenses (BCLs) have been widely studied as an alternative to eye drops due to their ability to increase the drug residence time and bioavailability as well as improve patient compliance. While silicone hydrogel polymers are commonly used in drug-eluting BCLs due to their transparency, mechanical properties and high oxygen permeability, gelatine hydrogels are also clear, flexible and have high oxygen permeability and may therefore be suitable contact lens materials. Moreover, the rheological properties of gelatine hydrogels allow their use as inks in extrusion-based 3D printers, therefore opening the door to a wide range of applications. Drug-loaded gelatine methacryloyl (GelMA) BCLs with different concentrations of poly (ethylene glycol) diacrylate (PEGDA) were prepared using solvent casting and 3D printing. The prepared lenses were characterised for their swelling ratio, in vitro degradation, and drug release properties. The results showed that the incorporation of 10% PEGDA improved the lenses' resistance to handling and protected them during degradation testing, reduced the swelling ratio and prolonged the release of dexamethasone (DEX). Both techniques were deemed suitable to use in the manufacturing of drug-eluting BCLs noting that the optimal formulation may vary according to the preparation technique utilised.

Development of a microencapsulated probiotic delivery system for New Zealand black-footed abalone (Haliotis iris).

Conventional methods of probiotics delivery to farmed aquatic animals are not efficient due to loss of probiotic's viability before the probiotics can reach their site of action. This study aims to develop a microencapsulated probiotic delivery system for black-footed abalone (Haliotis iris). An emulsion technique was used to encapsulate probiotic bacteria within chitosan-coated alginate microparticles (CALG). The efficacy of CALG microparticles in delivering probiotics to abalone was assessed using ex vivo and in vivo experiments. Microparticles (113 ± 4 µm) with encapsulation efficiency of more than 75% were developed using an internal gelation formulation approach. The ex vivo release experiments revealed the lack of probiotic discharge in the first 6 h of incubating CALG in seawater followed by a slight bacterial release within the next 20 h. The exposure of CALG microparticles to simulated gastric and intestinal media showed a significantly higher release of encapsulated bacteria in the simulated intestinal medium. The results of feeding trial revealed that the number of probiotic bacteria in probiotic-fed abalone was significantly higher than the one in the control animals. The results suggest that CALG microparticles can be used as a controlled release system for delivering viable probiotic bacteria to the gastrointestinal tract of abalone.

The impact of curcumin-graphene based nanoformulation on cellular interaction and redox-activated apoptosis: An in vitro colon cancer study.

Natural plants derivatives have gained enormous merits in cancer therapy applications upon formulation with nanomaterials. Curcumin, as a popular research focus has acquired such improvements surpassing its disadvantageous low bioavailability. To this point, the available research data had confirmed the importance of nanomaterial type in orienting cellular response and provoking different toxicological and death mechanisms that may range from physical membrane damage to intracellular changes. This in turn underlines the poorly studied field of nanoformulation interaction with cells as the key determinant in toxicology outcomes. In this work, curcumin-AuNPs-reduced graphene oxide nanocomposite (CAG) was implemented as a model, to study the impact on cellular membrane integrity and the possible redox changes using colon cancer in vitro cell lines (HT-29 and SW-948), representing drug-responsive and resistant subtypes. Morphological and biochemical methods of transmission electron microscopy (TEM), apoptosis assay, reactive oxygen species (ROS) and antioxidants glutathione and superoxide dismutase (GSH and SOD) levels were examined with consideration to suitable protocols and vital optimizations. TEM micrographs proved endocytic uptake with succeeding cytoplasm deposition, which unlike other nanomaterials studied previously, conserved membrane integrity allowing intracellular cytotoxic mechanism. Apoptosis was confirmed with gold-standard morphological features observed in micrographs, while redox parameters revealed a time-dependent increase in ROS accompanied with regressive GSH and SOD levels. Collectively, this work demonstrates the success of graphene as a platform for curcumin intracellular delivery and cytotoxicity, and further highlights the importance of suitable in vitro methods to be used for nanomaterial validation.

Methods for quantification of cannabinoids: a narrative review.

BACKGROUND: Around 144 cannabinoids have been identified in cannabis plant, among them tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prominent ones. Because of the legal restrictions on cannabis in many countries, it is difficult to obtain standards to use in research; nonetheless, it is important to develop a cannabinoid quantification technique with pharmaceutical applications for quality control of future therapeutic cannabinoids. METHOD: To find relevant articles for this narrative review paper, a combination of keywords such as medicinal cannabis, analytical, quantification and cannabinoids were searched for in PubMed, EMBASE, MEDLINE, Google Scholar and Cochrane Library (Wiley) databases. RESULTS: The most common cannabinoid quantification techniques include gas chromatography (GC) and high-performance liquid chromatography (HPLC). GC is often used in conjunction with mass spectrometry (MS) or flame ionization detection (FID). The major advantage of GC is terpenes quantification however, for evaluating acidic cannabinoids it needs to be derivatised. The main advantage of HPLC is the ability to quantify both acidic and neutral forms of cannabinoids without derivatisation which is often with MS or ultraviolet (UV) detectors. CONCLUSION: Based on the information presented in this review, the ideal cannabinoid quantification method is HPLC- MS/MS for the cannabinoids.

Dual platform based sandwich assay surface-enhanced Raman scattering DNA biosensor for the sensitive detection of food adulteration.

Surface enhanced Raman scattering (SERS) DNA biosensing is an ultrasensitive, selective, and rapid detection technique with the ability to produce molecule-specific distinct fingerprint spectra. It supersedes the long amplicon based PCR assays, the fluorescence and spectroscopic techniques with their quenching and narrow spectral bandwidth, and the electrochemical detection techniques using multiplexing. However, the performance of the SERS DNA biosensor relies on the DNA probe length, platform composition, both the presence and position of Raman tags and the chosen sensing strategy. In this context, we herein report a SERS biosensor based on dual nanoplatforms with a uniquely designed Raman tag (ATTO Rho6G) intercalated short-length DNA probe for the sensitive detection of the pig species Sus scrofa. In the design of the signal probe (SP), a Raman tag was incorporated adjacent to the spacer arm, followed by a terminal thiol modifier, which consequently had a strong influence on the SERS signal enhancement. The detection strategy involves the probe-target DNA hybridization mediated coupling of the two platforms, i.e., the graphene oxide-gold nanorod (GO-AuNR) functionalized capture probe (CP) and SP-conjugated gold nanoparticles (AuNPs), consequently enhancing the SERS intensity by both the electromagnetic hot spots generated at the junctions or interstices of the two platforms and the chemical enhancement between the AuNPs and the adsorbed intercalated Raman tag. This dual platform based SERS DNA biosensor exhibited outstanding sensitivity in detecting pork DNA with a limit of detection (LOD) of 100 aM validated with DNA extracted from a pork sample (LOD 1 fM). Moreover, the fabricated SERS biosensor showed outstanding selectivity and specificity for differentiating the DNA sequences of six closely related non-target species from the target DNA sequences with single and three nucleotide base-mismatches. Therefore, the developed short-length DNA linked dual platform based SERS biosensor could replace the less sensitive traditional methods of pork DNA detection and be adopted as a universal detection approach for the qualitative and quantitative detection of DNA from any source.

A 3D printed chitosan-pectin hydrogel wound dressing for lidocaine hydrochloride delivery.

A chitosan-pectin (CS-PEC) biopolymeric hydrogel wound dressing was investigated for lidocaine delivery. Here we demonstrate for the first time the feasibility of three-dimensional (3D) printed CS-PEC hydrogel incorporating the local anaesthetic drug lidocaine hydrochloride (LDC) as a potential wound dressing candidate. The hydrogels were prepared by physical crosslinking of CS and PEC polysaccharides. The scaffolds were printed using an extrusion-based 3D printer using a mechanical positive displacement dispensing system followed by lyophilisation. The 3D printed hydrogels showed good printability, dimensional integrity and self-adhesion to skin. The high swelling ratio and water absorption of 3D printed hydrogels indicated suitability for absorbing exudates and maintaining a moist wound healing environment. Fourier transform infrared (FTIR) spectroscopy results indicated that the CS-PEC hydrogel was formed by hydrogen bonds. Incorporation of LDC in the hydrogel did not interfere with its functional stability. In vitro drug release studies of LDC over 6 h fitted the Korsmeyer-Peppas model. This work demonstrates the possibility of a 3D printed hydrogel as a suitable candidate for wound dressings.

Controlled release of dexamethasone from poly(vinyl alcohol) hydrogel.

This study investigated a chemically crosslinked poly(vinyl alcohol) (PVA) hydrogel controlled drug delivery system to deliver the anti-inflammatory drug dexamethasone (DEX). The PVA hydrogels, with different crosslinking densities, were characterized by swelling studies, electron scanning microscopy, viscosity, Fourier transform infrared spectroscopy (FTIR) and in vitro release assessment. Increasing crosslinking density slowed and decreased swelling and water absorption. FTIR analysis suggested DEX has possible interactions with the crosslinker and the PVA polymer. In vitro release of DEX from PVA hydrogels was sustained for 33 days and appeared to fit the Higuchi and Korsmeyer-Peppas models. This work indicates the likelihood of PVA hydrogel as a controlled drug release system for DEX for anti-inflammatory uses.

Patient access to medicines in two countries with similar health systems and differing medicines policies: Implications from a comprehensive literature review.

BACKGROUND: Countries with similar health systems but different medicines policies might result in substantial medicines usage differences and resultant outcomes. The literature is sparse in this area. OBJECTIVE: To review pharmaceutical policy research in New Zealand and Australia and discuss differences between the two countries and the impact these differences may have on subsequent medicine access. METHODS: A review of the literature (2008-2016) was performed to identify relevant, peer-reviewed articles. Systematic searches were conducted across the six databases MEDLINE, PubMed, Science Direct, Springer Links, Scopus and Google Scholar. A further search of journals of high relevance was also conducted. Using content analysis, a narrative synthesis of pharmaceutical policy research influencing access to medicines in Australia and New Zealand was conducted. The results were critically assessed in the context of policy material available via grey literature from the respective countries. RESULTS: Key elements regarding pharmaceutical policy were identified from the 35 research papers identified for this review. Through a content analysis, three broad categories of pharmaceutical policy were found, which potentially could influence patient access to medicines in each country; the national health system, pricing and reimbursement. Within these three categories, 9 subcategories were identified: national health policy, pharmacy system, marketing authorization and regulation, prescription to non-prescription medicine switch, orphan drug policies, generic medicine substitution, national pharmaceutical schedule and health technology assessment, patient co-payment and managed entry agreements. CONCLUSIONS: This review systematically evaluated the current literature and identified key areas of difference in policy between Australia and NZ. Australia appears to cover and reimburse a greater number of medicines, while New Zealand achieves much lower prices for medicines than their Australian counterparts and has been more successful in controlling national pharmaceutical expenditure. Delays in patient access to new therapies in New Zealand have considerable implications for overall patient access to medicines; however, higher patient co-payments and relative pharmaceutical expenditure in Australia and its effect upon patient access to medicines must also be considered.

Brinzolamide-loaded nanoemulsions: ex vivo transcorneal permeation, cell viability and ocular irritation tests.

The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC50) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ.

Development of a Long-Term Drug Delivery System with Levonorgestrel-Loaded Chitosan Microspheres Embedded in Poly(vinyl alcohol) Hydrogel.

This study reports on the fabrication of a controlled release system for the delivery of levonorgestrel (LNG) for long-term contraception. LNG was encapsulated in chemically cross-linked chitosan (CS) microspheres, and microspheres presented a spherical geometry with a good particle size distribution (polydispersity index (PDI) < 0.1). The LNG-CS microspheres were classified based on their particle size range, <63, 63-125, and 125-300 µm, where the 125-300 µm particles were selected to be incorporated into a physically cross-linked and annealed PVA hydrogel matrix to prolong the drug release. PVA concentrations and the annealing treatment influenced the swelling behavior of PVA hydrogels. Fourier transform infrared (FTIR) spectroscopy indicated that CS was successfully cross-linked through the formation of a Schiff base; the PVA hydrogel was formed through hydrogen bonding without reacting with LNG, which was only physically entrapped, thus maintaining its stability. Differential scanning calorimetry (DSC) showed that freeze-thaw and annealing processes increased the degree of crystallinity in the PVA hydrogel. In vitro drug release assessments for all formulations showed zero order without any burst release. Over a period of 100 days, 34, 27, and 21% of LNG was released from the CS-LNG microspheres in the size ranges < 63, 63-125, and 125-300 µm, respectively, while only 14, 11, and 9% of LNG was released when the CS-LNG microspheres were incorporated into 10, 15, and 20% PVA hydrogels, respectively. The drug release kinetics exhibited both diffusion- and swelling-controlled mechanisms following the Korsmeyer-Peppas model. This work presents a promising delivery system for long-term contraception with controlled zero-order release behaviors.