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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]

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]

A critical problem associated with delivery of bovine lactoferrin (bLf) by the oral route is low bioavailability, which is derived from the enzymatic degradation in the gastrointestinal tract and poor permeation across the intestinal epitheliums. Particulate carrier systems have been identified to protect bLf against proteolysis via encapsulation. This study aimed to evaluate the physico-chemical stability of bLf-loaded liposomes and solid lipid particles (SLPs) modified by pectin and chitosan when exposed to various stress conditions. Transmission electron microscopy results showed liposomes and SLPs had a classic shell-core structure with polymer layers surrounded on surface, but the structure appeared to be partially broken after digestion in simulated intestinal fluid (SIF). Although HPLC and sodium dodecyl sulphate-polyacrylamide gel electrophoresis methods qualitatively and quantitatively described either liposomes or SLPs could retain intact bLf against proteolysis in SIF to some extent, all liposome formulations showed rapid rate of lipolysis mediated by pancreatic enzymes. On the other hand, all SLP formulations showed higher heat resistance and greater electrolyte tolerance compared to liposome formulations. After 180 days storage time, liposome-loaded bLf was completely degraded, whereas almost 30% of intact bLf still remained in SLP formulations. Overall, SLPs are considered as primary choice for oral bLf delivery. [ABSTRACT FROM AUTHOR]

Oral delivery is the most common method for bovine lactoferrin ( bLf) administration. However, the presence of proteolytic enzymes in the stomach and intestine limits the effective absorption of bLf within the gastrointestinal ( GI) tract. To determine the extent of bLf proteolysis, several digestion models were developed using luminal extracts and mucosal homogenates isolated from four regions of rat intestine: duodenum, jejunum, ileum, and proximal colon. The kinetics of bLf degradation followed a pseudo-first-order rate, and almost complete hydrolysis of bLf was observed in the luminal extracts, indicating that bLf is more susceptive to luminal peptidases rather than mucosal enzymes. Moreover, a significant reduction in bLf proteolysis was observed in the presence of soybean trypsin inhibitor ( SBTI), bestatin, and bacitracin, suggesting that there exist trypsin-like and aminopeptidase-like proteases, which play a key role in the degradation of bLf in the intestine. Lactoferrin was then encapsulated in several lipid-based delivery systems including liposomes and solid lipid particles ( SLPs) with polymer modification, showing at least 50% of intact bLf remaining after 6 h of digestion compared with native bLf. These findings suggest that particle encapsulation may modulate protein digestion and possibly achieve sufficient oral bioavailability of bLf. [ABSTRACT FROM AUTHOR]

Bioadhesive liposomes and solid lipid particles (SLPs) modified by pectin and chitosan for oral administration of bovine lactoferrin ( bLf) were prepared using a 24 full-factorial design to identify the key formulation variables influencing particle size and drug entrapment efficiency (EE). Netlike structures of the polymer-particle mixture consisting of a polymeric network in which multiple particles were imbedded were observed by scanning electron microscopy (SEM). Chemical stability of bLf after encapsulation into pectin- and chitosan-modified liposomes and SLPs was confirmed by Fourier transform infrared spectra (FTIR). Bovine lactoferrin was located within phospholipid bilayer, whereas in SLPs bLf was within the matrix. The crystalline nature of bLf after encapsulation was investigated by differential scanning calorimetry (DSC) of drug-loaded particles, indicating amorphous dispersion of bLf in the polymer-lipid matrix of pectin- and chitosan-modified liposomes and SLPs. In vivo pharmacokinetic investigation of bLf in pectin- and chitosan-modified liposomes and SLPs showed prolonged mean residence time (MRT) of bLf in rat blood and increased the relative bioavailability (Fbio%) by 1.95- to 2.69-fold compared with free bLf. The developed carrier systems are considered to be promising vehicles for oral 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]