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With the growing prevalence of diabetes, there is an urgent demand for a user‐friendly treatment option that minimizes side effects related to the use of subcutaneous injections. Scientists have dedicated over a century to developing an oral dosage form of insulin that can be administrated orally. The oral route of administration is the most desirable route for regularly dosed drugs in terms of safety and patient compliance. However, oral delivery of insulin remains a formidable challenge due to its intrinsically limited ability to cross the intestinal epithelium membrane and susceptibility to enzymatic degradation. This article reviews oral insulin research over the past decade, with a particular focus on surface modifications of nanoparticles (NPs). Various strategies involving controlling surface charges, utilizing protective proteins, and targeting specific receptors with ligands have been explored. Notably, surface modifications of the NPs for targeting specific intestinal receptors have shown promise in enhancing insulin oral absorption and bioavailability. Advanced technologies such as oral microneedles and gene therapy have also been developed, but their safety requires further assessment. Despite encouraging preclinical results across numerous strategies, the current clinical evidence is less optimistic. In summary, the present findings highlight the substantial journey that still lies ahead before achieving successful oral delivery of insulin. Practical Applications: This review provides a summary of recent progress in oral insulin delivery, particularly highlighting surface‐modified functional nanoparticles serving as an effective drug delivery system, which offers valuable information to the researchers. Due to the limited effectiveness of oral protein drugs caused by biological barriers, innovative technologies and drug delivery systems have been developed to overcome these obstacles and achieve therapeutic goals. This review concluded that surface modifications to nanoparticles can improve insulin stability and permeability, thereby enhancing oral bioavailability. It could assist researchers in developing more effective and patient‐friendly oral drug delivery systems. [ABSTRACT FROM AUTHOR]

Aim: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. Methods: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model. Results and Discussion: The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs. Conclusion: This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides. [ABSTRACT FROM AUTHOR]

Energy supplementation may reduce oxidative stress by correcting a negative energy balance, but in some contexts, it has been shown to increase oxidative stress, especially at peak lactation. The current experiment examined if a pelleted energy supplement with or without the addition of Lactobacillus-fermented seaweed or seaweed plus terrestrial plants extracts affected oxidative stress of ewes from late gestation through to weaning and ewe and lamb production from lambing to weaning. Treatments were either no supplement (CON−), a pelleted supplement only (CON+, 100 g/ewe per d), CON+ with seaweed extract only (SWO, 10 mL/ewe per day), or CON+ with seaweed plus an arrangement of terrestrial plant extract (SWP, 10 mL/ewe per d). Ewes (n = 160; mean initial BW = 72.3 ± 9.5 kg [mean ± SD]) were randomized to pastures (n = 4 pastures per treatment with 10 ewes each). After lambing, ewes with twins were reallocated to pastures (n = 3 pastures per treatment with 10 ewes each) according to lambing date. At 4 wk in milk, supplementation tended to reduce total antioxidant status (TAS; P = 0.10) and increased glutathione peroxidase (GPx) activity compared with non supplemented ewes (P = 0.04). The addition of seaweed and terrestrial plants extracts to the concentrate, that is, SWO and SWP, increased TAS and reduced GPx activity compared with CON+ (P < 0.01). Supplementation increased milk yield at weeks 4, 6, and 8 of lactation, and protein, lactose, and total milk solids yield at peak lactation (week 4; P < 0.05). The CON− ewes had greater somatic cell count than the supplemented ewes at weeks 4, 8, and 10 of lactation (P = 0.03). Our results suggest that energy supplementation, alone, increases oxidative stress of lactating ewes, which may relate to increased oxidative phosphorylation. Most importantly, these results indicate that in situations where energy supplementation is needed to increase animal performance, negative effects of energy supplementation around peak lactation can be offset by the addition of Lactobacillus-fermented plant extracts (SWO and SWP) to improve antioxidant status. [ABSTRACT FROM AUTHOR]

The use of Spratt's dog cakes is well documented in the diaries and reminiscences of many early Antarctic expedition members. Commercially produced dog food was promoted by the likes of Spratt's as an advanced form of animal nutrition and would have been of interest to expedition planners who were already concerned with the nutritional requirements of expedition members. An approximately 100-year-old dog cake recovered from Antarctica was compared by chemical analysis and spectroscopic methods with a series of model dog cakes and a commercial dog biscuit to determine the composition and calorific content. The presence of bone fragments within the dog cake was confirmed, whereas starch in the bulk matrix of the sample was consistent with being a mixture of wheat and oat flour, while only minimal fat or oil was present. Calorific content, while insufficient compared to a modern feed for high-performance dogs, would nonetheless have been a valuable addition to the use of dried or frozen whole meat such as seal, fish, or pemmican and contributed additional energy compared to meat alone. [ABSTRACT FROM AUTHOR]

The widespread use of silver nanoparticles (AgNPs) as a bactericide will ultimately result in their increased concentration in soils. We sought to determine the likely mobility, toxicity, and plant uptake of Ag applied to soil as either AgNPs or Ag+. We measured the solubility, toxicity, and plant uptake of both AgNPs and Ag+ in an immature Pallic soil, a Templeton loamy silt (pH = 5.1), and a granular silt loam (pH = 6.0). The sorption of AgNPs by the test soils was significantly greater than Ag+, and both moieties were more strongly sorbed at lower concentrations and higher pH values. Between pH 4 and 8, distribution coefficient (KD) values increased from <10 up to ∼500 L kg−1 for Ag+, and from 100 to 10,000 L kg−1 for AgNPs. There was strong evidence that our citrate‐coated AgNPs were transformed into Ag+ during the course of the plant growth experiments, and plant responses were similar for both the Ag+ and AgNP treatments. Soil concentrations >100 mg kg−1 significantly reduced the biomass of Lolium perenne L. and resulted in foliar concentrations of up to 10 mg kg−1 dry matter. At a soil concentration of 70 mg kg−1, silverbeet [Beta vulgaris L. ssp. maritima (L.) Arcang.] and spinach (Spinacia oleracea L.) accumulated 5 to 10 mg Ag kg−1, which may present a human health risk. Regarding citrate‐coated AgNPs, the environmental impact of release is largely determined by the equivalent mass concentration of Ag+, into which they will ultimately transform. Given the widespread interest in AgNPs, there is limited knowledge on the behavior of Ag+ in soil and this should be the subject of future research. Core Ideas: Citrate‐coated Ag nanoparticles had greater soil sorption than Ag+.Sorption of both Ag nanoparticles and Ag+ increased at higher pH.Silver nanoparticles are ultimately unstable and transform to Ag+.Phytotoxicity occurs at soil Ag concentrations >100 mg kg−1.Silver uptake by spinach and silverbeet may present a human health risk. [ABSTRACT FROM AUTHOR]

The functional food sector has shown tremendous growth in recent years with the application of probiotic bacteria as "food additives". The utilization of probiotic bacteria in food presents many challenges related to their growth, survival, viability, stability and functionality in food processing, storage and consumption as well as changes of sensory characteristics of probiotic foods. Although dairy foods are currently the most common food carrier to deliver probiotics, an increasing number of non-dairy food matrices exhibit potential for delivery of probiotics. This review provides more recent insight into the emergence of non-dairy probiotics products, the interactions between probiotics and different food matrices and the challenges in developing such products. Some of the technical issues are also reviewed and discussed. These issues include the efficacy of probiotic bacteria in non-chilled, low pH or high water activity foods; the potential loss of bacterial viability, additionally unwanted fermentation and changes of the sensory characteristics of food products which may result in poor microbiological quality and low acceptability to consumers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Beta-carotene is a potent antioxidant for maintaining human health. However, its oral absorption is low due to poor aqueous solubility of less than 1 μg/ml. A microemulsion delivery system was designed to solubilize beta-carotene toward enhancing its oral bioavailability. From seven pseudoternary diagrams constructed, three systems were selected with large microemulsion areas suitable for oral administration and dilution in the predominately aqueous gastrointestinal fluids. Conductivity and rheology characterization were conducted along four dilution lines within the selected systems. Three pseudoternary-phase diagrams were selected with large microemulsion regions, >60% of the total phase diagram area, which provide microemulsions with higher drug-loading capacity. A phenomenon was observed by which both propylene glycol and Capmul MCM EP stabilize the microstructure of the microemulsions has been proposed based on the characterization studies. An optimal bicontinuous microemulsion formulation was selected comprising 12% orange oil, 24% Capmul MCM, 18% Tween 20, 6% Labrasol, 20% propylene glycol and 20% water, with a high beta-carotene loading capacity of 140.8 μg/ml and droplet size of 117.4 nm. In conclusion, the developed novel microemulsion formulation allows solubilizing beta-carotene and is a promising basis for further development as a functional beverage. [ABSTRACT FROM AUTHOR]

The viability of probiotics in non-dairy food products during storage is required to meet content criteria for probiotic products. This study investigated whether non-dairy foods could be matrices for probiotics. Selected probiotic bacteria were coated on non-dairy foods under two storage conditions, and viabilities were assessed. The non-dairy foods were coated with 5–7 log cfu g−1 of Lactobacillus acidophilus ATCC4356T, Lactobacillus plantarum RC30, and Bifidobacterium longum ATCC15707T. The coated non-dairy foods were stored at 20 °C and 20% relative humidity (RH) or 30 °C and 50% RH. Viability of probiotic bacteria was determined after 0, 2, and 4 weeks of storage. B. longum showed the highest survival at week 4 of 6.5–6.7 log cfu g−1 on wheat bran and oat, compared with 3.7–3.9 log cfu g−1 of L. acidophilus and 4.2–4.8 log cfu g−1 of L. plantarum at 20 °C 20% RH. Under the storage conditions of 30 °C 50% RH, survival of 4.5 log cfu g−1 of B. longum was also found on oat and peanut. This was two and four times higher than the population of L. acidophilus and L. plantarum, respectively. The results suggest that probiotics can survive on non-dairy foods under ambient storage conditions. However, the storage conditions, food matrices, and probiotic strains should be carefully chosen to maximize probiotic bacteria survival. [ABSTRACT FROM AUTHOR]

Collectively, many lactobacilli form a major group of health-promoting microorganisms. A subset of which are generally known as probiotics. Emergence of antibiotic-resistant strains is challenging human health and well-being, particularly antibiotic therapy for the treatment of bacterial infections. Lactobacilli may prevent gastrointestinal disruption during antibiotic therapy by helping to reestablish or maintain the normal microbiota of the intestine. To achieve this, lactobacilli must survive in the presence of coadministered antibiotics. Hence, antibiotic resistance of probiotics is an essential criterion for their screening and selection, provided of course that they do not pose a threat by way of the transfer of antibiotic resistance genes to other bacteria. This article addresses the types of antibiotic resistance and transfer mechanisms, the antibiotic resistance profile of probiotic lactobacilli, as well as the benefits associated and concerns raised with antibiotic resistance of probiotic bacteria. [ABSTRACT FROM PUBLISHER]

In laboratory settings, the ability of bacteria and fungi to degrade many environmental contaminants is well proven. However, the potential of microbial inoculants in soil remediation has not often been realized because catabolically competent strains rarely survive and proliferate in soil, and even if they do, they usually fail to express their desired catabolic potential. One method to address the survival problem is formulating the microorganisms with physical and chemical support systems. This study investigates the survival ofPseudomonassp. strain ADP in sterile soil and its retention of atrazine-degrading functionality. Assessment was conducted with free and zeolite-immobilized bacteria incorporated into the soil.Pseudomonassp. strain ADP remained viable for at least 10 weeks when stored at 15°C in sterile soil. Cell numbers increased for both free and zeolite-immobilized bacteria during this period, except for free cells when grown in Miller's Luria-Bertani medium, which exhibited constant cell numbers over the 10 weeks. Only the zeolite-immobilized cell retained full functionality to degrade atrazine after 10 weeks in sterile soil regardless of the medium used to culturePseudomonassp. strain ADP. Functionality was diminished in free-cell inoculations except when using an improved culture medium. Survival of zeolite-immobilizedPseudomonassp. strain ADP separated from the soil matrix after 10 weeks’ incubation was significantly (p< .05) greater than in soil inoculated with free cells or in the soil fraction inoculated by release from zeolite-immobilizedPseudomonassp. strain ADP. [ABSTRACT FROM AUTHOR]

Background: (+)-catechin, as the most common catechin isomer, is recognized to be an antioxidant which benefits the skin in many ways. The purpose of the present study was to prepare and evaluate a suitable liposomal delivery systems for (+)-catechin topical application. Methods: In this study, catechin-loaded conventional liposomal delivery system, deformable conventional liposomal delivery system and deformable liposomes prepared by reverse-phase evaporation (REV) method were compared. The three systems were characterized for liposome particle size, zeta-potential, entrapment efficiency, drug release, permeability across porcine skin and catechin deposition in the skin. Results: It was revealed that the size of deformable conventional liposomes before freeze-drying and deformable REV liposomes after freeze-drying range from 335.6 ± 71.7 nm to 551.1 ± 53.4 nm, respectively, which were considered to be suitable for skin delivery. The deformable REV liposomes had a higher aqueous volume and thus were able to entrap greater amounts of hydrophilic (+)-catechin (50.0 ± 5.9%) compared to conventional (30.0 ± 3.8%) and deformable conventional liposomes (36.1 ± 4.6%). All liposomal formulations exhibited a prolonged catechin release. Compared to deformable liposomes, the REV deformable liposomes showed a significantly better deposition of (+)-catechin while catechin solution did not permeate into the porcine ear skin. Conclusion: Among all formulations studied, deformable REV liposomes were considered to be favorable for catechin topical delivery. [ABSTRACT FROM AUTHOR]

ABSTRACT The objective of this study was to qualitatively and quantitatively evaluate bovine lactoferrin (bLf) and its stability using a rapid RP-HPLC method. bLf could be rapidly detected within 20 min and quantitated at levels down to 5 µg/mL, and the equation of linearity was y = 86.10 x + 178.31 with the correlation coefficient ( r2) 0.9997. Quantitative data obtained in the present study proved the improved RP-HPLC method to be a sensitive and accurate analytical tool for bLf determination. The proteolytic cleavage of bLf in simulated human gastrointestinal fluids was further analyzed by RP-HPLC, and found to follow pseudo-first-order kinetics. The typical equation obtained by pepsin was log10 [ At]/[ A0] = −0.03 x ( r2 = 0.85), and log10 [ At]/[ A0] = −0.01 x ( r2 = 0.81) for trypsin and chymotrypsin combination. Pepsinolysis of bLf in simulated gastric fluid was relatively fast with the half-life t1/2 23.1 min. The digestion of bLf in simulated intestinal fluid was slower with about a 3-fold increase in half-life (69.3 min). After the complete proteolysis of bLf, small cleaved peptide fragments were fully separated and identified by RP-HPLC. The proteolytic study indicated that this validated RP-HPLC was able to evaluate bLf stability though monitoring the derivatization products. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Context: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature. Objective: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of β-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG. Materials and methods: Oscillation viscometry was used to evaluate the gel character by measuring flow index ( N), storage (G′) and loss (G″) moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells. Results: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly ( p < 0.001) from 3.65 ± 0.43 to 34.30 ± 8.90 (dextran) and 805.80 ± 5.30 (PEG) 24 h after polymer addition. In vitro release profiles showed significantly ( p < 0.05) reduced AUC0-8 h, k and percentage of drug released from two-phase systems compared to β-glucan dispersions, with the PEG system resulting in the lowest amount released over 8 h (15.1 ± 1.6%). Discussion: The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense β-glucan gel. Conclusion: 1.5% (w/w) β-glucan combined with PEG at a ratio of 1:3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release. [ABSTRACT FROM AUTHOR]

Liquid polymeric systems that can undergo phase change (sol to gel) upon administration into the teat canal of cow''s mammary gland can serve as a physical barrier to invading pathogens and can also serve as a reservoir for controlled release of therapeutic agents. The aim of the study was to investigate the phase behavior, rheological and mechanical properties of selected in situ gelling systems. Six in situ gelling polymer formulations were identified using phase behavior studies. Rheological studies revealed pseudoplastic flow with thixotropy. All six formulations showed significantly different viscosity, pseudoplasticity and thixotropy values except for CMC1 and HPMC2 which where statistically similar. The gel strength was dependent on the solvent system used and amount of water in the system. These in situ gelling systems have the potential to serve as a platform for development of intramammary formulations intended for administration into the teat canal of the cow''s mammary gland. They can serve as a physical barrier or a matrix for controlled drug release. [ABSTRACT FROM AUTHOR]

The purpose of this study was to reengineer a commercially available intravaginal insert containing 1.9 g progesterone (CIDR intravaginal insert) for a 7-day insertion period in cattle. The reengineering process resulted in a reduced initial drug load (1.38 g) and a reduction in the residual drug load following insertion, while at the same time maintaining the biological performance of the insert. The in vitro and in vivo pharmaceutical properties of the commercially available CIDR intravaginal insert were characterized initially to gain a thorough understanding of the factors that affected progesterone release from the insert. The effect of changing a selection of formulation and physical variables of the insert was also investigated (including surface area, drug load, addition of pore forming materials, silicone shore hardness and drug particle size). The knowledge gained from these studies was used to define the characteristics of the reengineered insert which was then manufactured and shown to be bioequivalent and clinically equivalent to the commercially available insert. [Copyright &y& Elsevier]

This paper reports experiments conducted to research, develop and clinically evaluate an injection molded intravaginal insert manufactured from the biodegradable polyester poly(ε-caprolactone). The study demonstrated that it is possible to engineer poly(ε-caprolactone) into a shape that is well retained, and can be used as a platform for the controlled delivery of progesterone via the vagina of cows. Field evaluation showed that the poly(ε-caprolactone) intravaginal inserts containing 10% (w/w) progesterone were at least as effective clinically as the commercially available CIDR intravaginal insert. [Copyright &y& Elsevier]

Treatment and prevention of cattle mastitis remains a formidable challenge due to the anatomical and physiological constraints of the cow udder. In this study, we investigated polymeric excipients and solvents that can form, (when combined) novel, non-toxic and biocompatible in situ gelling formulations in the mammary gland of bovine cattle. We also report on a new approach to screen intramammary formulations using fresh excised cow teats. Fourteen hydrophilic polymers and six solvents were evaluated for in vitro cytotoxicity and biocompatibility towards cultured bovine mammary epithelial cells (MAC-T), microscopic and macroscopic examination upon contact with excised cow teats. No significant cytotoxicity (p > 0.05) was observed with polyethylene oxides, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium alginate and xanthan gum. Polycarbophil and carbopol polymers showed significantly higher cytotoxicity (p < 0.05). Concentration-dependent cytotoxicity was observed for glycerin, propylene glycol, polyethylene glycol 400, ethanol, N-methyl-2-pyrrolidone and 2-pyrrolidone, with the 2-pyrrolidone solvents showing higher cytotoxic effects (p < 0.05). In situ gelling formulations comprising hydroxypropyl methylcellulose or carboxymethyl cellulose and solvents in specific ratios were biocompatible at higher concentrations with MAC-T cells compared to alginates. All investigated formulations could undergo in situ sol-to-gel phase transformation, forming non-toxic gels with good biocompatibility in excised cow teats hence, showing potential for use as intramammary carriers for sustained drug delivery. [ABSTRACT FROM AUTHOR]

Electrospun nanofibers have been extensively studied for encapsulated drugs releasing from the inside of the fiber matrix, but have been barely looked at for their potential to control release as a semi-permeable membrane. This study investigated molecular transport behaviors across nanofiber membranes with different micro-structure sizes and compositions. Four types of membranes were made by 5% and 10% poly (ε-caprolactone) (PCL) solutions electro-spun with or without 50 nm calcium carbonate (CaCO3) nanoparticles. The membranes were tested for thickness, fiber diameter, pore size, porosity, tensile strength and elongation, contact angle of water and their impacts on molecular transport behaviors. The presence of the CaCO3 nanoparticles made the 5% membranes stronger and stiffer but the 10% membranes weaker and less stiff due to the different (covering or embedded) locations of the nanoparticles with the corresponding fibers. Solute transport studies using caffeine as the model drug found the 5% membranes further retarded release from the 10% membranes, regardless of only half the amount of material being used for synthesis. The addition of CaCO3 nanoparticles aided the water permeation process and accelerated initial transports. The difference in release profiles between 5% and 10% membranes suggests different release mechanisms, with membrane-permeability dominated release for 5% PCL membranes and solute-concentration-gradient dominated release for 10% PCL membranes. [ABSTRACT FROM AUTHOR]

An introduction is presented in which teh editor discusess topics within the issue including nano-structured drug delivery systems; antimicrobial iron oxide magnetic nanoparticles; and nanogel for effective oral insulin delivery.