Prolonged Drug Delivery Research Articles

Degradable nanohydrogel with high doxorubicin loadings exhibiting controlled drug release and decreased toxicity against healthy cells.

A new nanogel/drug carrier of 100-150nm size, based on poly(N-isopropylacrylamide-co-sodium acrylate) and degradable crosslinker (cystine derivative), was synthesized. Using the electrostatic interactions between the carboxylic groups in the polymer network and the protonated amine groups of doxorubicin it was possible to load the drug into the carrier to a very high level of 28-30% relative to the dry mass of the polymer. The presence of the -S-S- groups made the polymer network susceptible to degradation by glutathione. The size of the nanoparticles was small enough to enable them to easily penetrate the cells. The MTT assay indicated that compared to free doxorubicin the nanogel particles loaded with doxorubicin were more cytotoxic against the MCF-7 and A2780 cancer cells, while they were 150 times less toxic against the MCF-10A healthy cells. The new carrier nanoparticles appeared also to be useful for prolonged drug delivery.

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing.

Implantable drug delivery devices offer many advantages over other routes of drug delivery. Most significantly, the delivery of lower doses of drug, thus, potentially reducing side-effects and improving patient compliance. Three dimensional (3D) printing is a flexible technique, which has been subject to increasing interest in the past few years, especially in the area of medical devices. The present work focussed on the use of 3D printing as a tool to manufacture implantable drug delivery devices to deliver a range of model compounds (methylene blue, ibuprofen sodium and ibuprofen acid) in two in vitro models. Five implant designs were produced, and the release rate varied, depending on the implant design and the drug properties. Additionally, a rate controlling membrane was produced, which further prolonged the release from the produced implants, signalling the potential use of these devices for chronic conditions.

Evaluation of mucoadhesive dexamethasone sodium phosphate gel in the treatment of arecoline-induced oral submucous fibrosis in wister albino rats: A cross-sectional study.

The present work aimed to prepare an oral mucoadhesive gel of dexamethasone sodium phosphate to serve the purpose of treating oral submucous fibrosis by incorporating the drug in a polymeric matrix to facilitate the localisation of the drug at the absorption site, to prolong drug delivery and to provide patient convenience. The formulations F1, F2 and F3 were prepared using 2, 2.5 and 3% of carboxymethyl cellulose sodium, formulations F4, F5 and F6 were prepared using 2, 2.5 and 3% of hydroxypropyl methylcellulose, respectively, and formulations F7, F8 and F9 were prepared using equal mixtures of carboxymethyl cellulose sodium and hydroxypropyl methylcellulose in the concentrations of 1, 1.25 and 1.50%, respectively. The prepared formulations were subjected for screening of physicochemical parameters, viz, homogeneity, grittiness, viscosity studies, spreadability, extrudability, mucoadhesive strength, pH, drug content uniformity, in vitro drug diffusion, Fourier transform infrared spectroscopy spectral analysis and stability studies. Among the nine formulations prepared, the formulation F8 containing 1.25% carboxymethyl cellulose sodium, 1.25% hydroxypropyl methylcellulose having a mucoadhesive strength of 12.600 ± 0.01 g and drug release of 88.473 ± 0.457% was considered as the promising one and was further used for in vivo study. Oral application of the gel for 4 months in arecoline-induced oral submucous fibrosis rats showed more than 80% reduction in fibrosis. The histopathological results supported these findings.

Formulation and Evaluation of Stability of a Topical Niosomal Gel ContainingCiclopirox Olamine

Background Superficial fungal infections can lead to many complications and serious issues. A diverse range of topical agents such as Ciclopirox olamine CPO are available for the treatment of dermatophytes bacteria yeasts and filamentous fungi. CPO is a highly lipophilic drug with very limited systemic absorption. Hence a specific dosage form of CPO was designed to increase its half-life for providing prolonged drug delivery as well as minimizing the side effects.Objective To develop a CPO-containing topical niosomal gel formula and to examine its stability and compatibility with others.Methodology The prepared niosomal gel was kept in sealed glass containers and preserved under refrigerated and room temperature conditions for 6 months. At the end of the 4th and 8th weeks and 3rd and 6th months the samples were collected and tested for various parameters.Results There were no significant changes in the physicochemical properties such as pH viscosity drug content and release profile.Conclusion Niosomal gel is stable when refrigerated as well as at room temperature.Keywords Ciclopirox Stability study Niosomal gel Fungal infectionnbsp

Recent advances in nanoscopic drug delivery systems for the treatment of glaucoma

AbstractNeuroprotection for glaucoma is still an unmet medical need and a proper drug delivery to the posterior segment of the eye is crucial. During the last decade, researchers have focussed their attention in the development of new drug delivery systems such as nanostructured lipid carriers, liposomes and polymeric nanoparticles. These nanoscopic systems overcome ocular barriers and provide a prolonged drug delivery on the target tissue avoiding adverse effects of the encapsulated drugs. During this course, recent advances and future perspectives in nanoscopic drug delivery systems for the treatment of glaucoma would be reviewed. Moreover, among several drug delivery systems, biodegradable polymeric nanoparticles have been proven to constitute a safe and suitable vehicle to encapsulate a wide range of drugs and be administrated as eye‐drops. Therefore, poly‐lactic‐co glycolic acid (PLGA) in addition to be biodegradable, biocompatible and non‐toxic, have demonstrated to be an effective drug carrier for ocular drug delivery. In this sense, Memantine loaded PLGA nanoparticles functionalized with polyethylene glycol (MEM‐NP) constitute a suitable neuroprotective strategy to increase MEM availability. MEM‐NP adminstered as eye‐drops confirmed to be safe, well‐tolerated and neuroprotective in an experimental glaucoma model. Nanoscopic systems could be the key for the efficient topical administration of neuroprotective compounds glaucoma treatment.

Treatment of oxidative stress-induced pain and inflammation with dexketoprofen trometamol loaded different molecular weight chitosan nanoparticles: Formulation, characterization and anti-inflammatory activity by using in vivo HET-CAM assay

Angiogenesis is a fundamental process of wound healing, embryogenesis etc. but occurs in cancer and chronic inflammation pathologically. HET-CAM assay is a useful, well established and animal alternative test to screen anti-inflammatory potentials of pharmaceutical products as well as nano-formulations. Dexketoprofen trometamol (DT) belongs to the nonsteroidal anti-inflammatory drug (NSAID) group which is a rapidly acting analgesic ingredient. Because DT has a short half-life, high and frequent dosing is used in treatment. The need of design and producing a new oral prolonged-release dosage form containing DT is the major aim of the study with low dose and low side effects. Chitosan (CS) has been widely used in the pharmaceutical area because of its favorable biological properties. In this study, DT loaded CS nanoparticles (CS-NPs) were produced by spray drying method for oral drug delivery. Structures of CS-NPs were elucidated by particle size, zeta potential, SEM, DSC, FT-IR and 1H NMR. High encapsulation efficiency was obtained (73–84%) for the prepared formulations. In vitro release was examined in pH 1.2 buffer and pH 6.8 buffer. DT-loaded CS-NPs showed prolonged release, particularly at pH 6.8. Weibull kinetic model was found to fit best to DT release from CS-NPs in both release medium. The anti-inflammatory activity of optimum formulation (M-DT) was examined using the in vivo HET-CAM assay. The anti-inflammatory activity results indicated that M-DT coded NPs formulation showed significantly good anti-inflammatory potential with closer inhibition value to the standard anti-inflammatory DT at one fifth lower dosage. According to the proposed method and results it can be successfully applicable to the NP preparation containing DT and it could be concluded that DT loaded CS-NPs seem to be a promising prolonged release drug delivery system for oral administration with low dose and high efficiency.

Porous poly(ε-caprolactone) implants: A novel strategy for efficient intraocular drug delivery

This work reports the development of porous poly (ε-caprolactone) (PCL)-based intraocular implants, prepared by green supercritical carbon dioxide (scCO2) foaming/mixing method (SFM), to produce implants that degrade faster than typical slow-degrading PCL-based implants. The higher porosities and surface areas of these implants led to faster degradation rates at in vitro accelerated alkaline conditions than low porosity/surface area implants prepared by hot melting processing. These porous implants also presented distinct (faster) release rates of a test-drug (dexamethasone). Additionally, these porous devices did not cause cell death and did not reduce the number of neurons, indicating that are not toxic to retinal cells. We further explored the impact of PCL-based implant to the retina by in vivo evaluation and histological analysis. Implants were surgically inserted in the vitreous of Wistar rats, and their presence did not change the function, structure and anatomy of the retina. These devices demonstrated a good intraocular tolerance, further confirming their viability for prolonged drug delivery applications. Further comprehensive studies based on this promising preliminary assessment and proof-of-concept could enable its future translation to clinical protective strategies for retinal diseases.

Design and development of artemisinin and dexamethasone loaded topical nanodispersion for the effective treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) is a disease affecting the macula by the new blood vessels formation. AMD is widely treated with a combination of anti-angiogenic and anti-vascular endothelial growth factor (VEGF) agents. The topical administration of nanodispersions showed enhanced ocular residence time with controlled and prolonged drug delivery to the disease site at the back of the eye. In the present study we developed and characterized nanodispersion containing anti-angiogenic (artemisinin) and anti-VEGF agent (dexamethasone) for the topical ocular administration in order to obtain a required drug concentration in the posterior part of the eye. The nanodispersions were prepared with varying concentration of polymer, polyvinyl pyrrolidone K90 and polymeric surfactant, Poloxamer 407. The nanodispersions were found to be smooth and spherical in shape with a size range of 12-26 nm. In-vitro drug release studies showed the 90-101% of artemisinin and 55-103% of dexamethasone release from the nanodispersions. The blank formulation with a high concentration of polymer and polymeric surfactant showed an acceptable level of haemolysis and DNA damage. The chorioallantoic membrane assay suggested that the nanodispersion possess good anti-angiogenic effect. Hence the formulated artemisinin and dexamethasone nanodispersion may have the great potential for the AMD treatment.

Expandable fibrous dosage forms for prolonged drug delivery

Many drug therapies could be greatly improved by dosage forms that reside in the stomach for prolonged time and release the drug slowly. In this work, therefore, slow-release fibrous dosage forms that expand rapidly in the gastric fluid to prevent their passage into the intestines are investigated. The dosage forms consisted of acetaminophen drug and a high-molecular-weight hydroxypropyl methyl cellulose (HPMC) excipient. Upon immersion in a dissolution fluid, they transitioned to viscous, and expanded in proportion to the square-root of time and the reciprocal of fiber radius. The normalized axial expansion was up to 100 percent by fifteen minutes, fast enough to convert a swallowable, 10-mm diameter disk into a gastroretentive, 20-mm diameter viscous gel. The drug was released slowly, eighty percent in 2–8.4 hours. Theoretical models show that the fibrous dosage forms expand rapidly due to the fast diffusion of dissolution fluid into the thin fibers. The fibers then coalesce into a uniform viscous gel, and the diffusion length increases from the radius of the thin fibers to the half-thickness of the gelated dosage form. Consequently, drug diffusion out is slow, and the twin requirements, fast expansion and prolonged drug release, are simultaneously satisfied.

Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation.

Both in vivo neuropharmacology and optogenetic stimulation can be used to decode neural circuitry, and can provide therapeutic strategies for brain disorders. However, current neuronal interfaces hinder long-term studies in awake and freely behaving animals, as they are limited in their ability to provide simultaneous and prolonged delivery of multiple drugs, are often bulky and lack multifunctionality, and employ custom control systems with insufficiently versatile selectivity for output mode, animal selection and target brain circuits. Here, we describe smartphone-controlled, minimally invasive, soft optofluidic probes with replaceable plug-like drug cartridges for chronic in vivo pharmacology and optogenetics with selective manipulation of brain circuits. We demonstrate the use of the probes for the control of the locomotor activity of mice for over four weeks via programmable wireless drug delivery and photostimulation. Owing to their ability to deliver both drugs and photopharmacology into the brain repeatedly over long time periods, the probes may contribute to uncovering the basis of neuropsychiatric diseases.

Application of paclitaxel-imprinted microparticles obtained using two different cross-linkers for prolonged drug delivery

Molecularly imprinted polymers (MIPs) are artificial materials processed to have cavities in the polymer structure which are capable of forming selective interactions with their molecular templates. Here, we report the synthesis of paclitaxel-imprinted microparticles and their application in prolonged drug delivery. Methacrylic acid was used as a functional monomer and 2-hydroxyethyl methacrylate was added to increase hydrophilicity of the obtained MIPs and therefore to improve compatibility with water solutions. The effect of two different cross-linkers, ethylene glycol dimethacrylate and trimethylolpropane trimethacrylate, on the final properties of obtained MIPs microspheres was examined. The influence of initial paclitaxel concentration as well as its contact time with MIPs microparticles on adsorption process was investigated. The release kinetics of paclitaxel from drug-loaded MIPs was found to be significantly depend upon the type of cross-linker used as well as the pH of the release medium. The highest cumulative release was observed at pH 7.4 for MIPs obtained using trimethylolpropane trimethacrylate as a cross-linker, reaching 85% in 50 h. The MIPs obtained using this cross-linker were characterized by IC50 comparable to the ones measured for pure paclitaxel. These results clearly indicate that the obtained MIPs microparticles have a large potential for prolonged drug delivery.

Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis

This study was conducted to develop an in situ thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, in vitro permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the in situ formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the in situ gel formulation. The cornea penetration of sertaconazole for the in situ gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.

Development of Implants for Prolonged Drug delivery

Despite being apopular and convenient route of drug delivery, the oral route has a number ofdisadvantages. Polymeric sub-dermal implants offer an alternative deliveryroute that may circumvent many of these challenges. In this study, implantswere designed using computer-aided design (CAD) software and fabricated using3D printing. The impact of implant design on the rate of drug release wasinvestigated using methylene blue as a model. It was found that drug releasecould be extended from 2 days to over 40 days as a result of changing implantdesign. Future work will focus on optimisation of implant design with the aimof producing degrading polymeric rate‑controlling membranes to further controldrug release and to conduct further invitro investigation with a drug compound.

Intra-articular drug delivery in OA

Local biomaterial-based drug delivery is a highly promising approach towards safe and effective pharmacological treatment of disease. High and effective local concentrations can be attained for a prolonged time period. The systemic burden is low, offering a new lease of life to drugs that are effective but have unacceptable systemic side effects. Moreover, smaller amounts of the drug are needed, thereby greatly reducing the costs of expensive biologicals-based treatments e.g. antibodies. Although nanomedicine approaches are gaining ground, systemically administered drug nanocarriers only reach body structures containing “leaky” blood vessels, such as tumours or organs like the liver and spleen, precluding their application for musculoskeletal disease. In contrast, prolonged delivery of drugs through local administration in bulk degrading biomaterial carriers, e.g. as microspheres or hydrogel depots, offers many advantages for diseases that are local in nature and inaccessible via the circulation, including osteoarthritis or intervertebral disc disease. The most likely first compounds to be delivered locally are FDA-approved drugs already in use. For osteoarthritis these could be corticosteroids and COX-2 inhibitors. Delivery biomaterials should be compatible and their local behaviour well characterized. Body location partially dictates the form of the biomaterial used, e.g. hydrogels will mostly be unsuitable for drug delivery in the diarthrodal joint. One PLGA-based product releasing triamcinolone acetonide is already on the market, and shows mixed results in human patients. We also found encouraging effects of TAA delivery in OA and RA pain, up until canine patients, although the presence of acute tissue damage is a contraindication. Delivery of celecoxib, both in OA and in IVDD, yielded long term inhibition of inflammation and pain, osteophyte formation and in the IVD even mild regeneration, up until in large animals including canine patients. In addition to providing hope for patients with chronic joint pain, extension of this approach towards other drugs and even biologicals may hold promise for regenerative approaches. Understanding the mechanisms of local drug release and effects of unusually high local concentrations will greatly aid development and efficacy of such new therapies.

Local release of rapamycin by microparticles delays islet rejection within the anterior chamber of the eye

The anterior chamber of the eye (ACE) has emerged as a promising clinical islet transplantation site because of its multiple advantages over the conventional intra-hepatic portal site. This includes reduced surgical invasiveness and increased islet graft survival rate. It also allows for enhanced accessibility and monitoring of the islets. Although the ACE is initially an immuno-privileged site, this privilege is disrupted once the islet grafts are re-vascularized. Given that the ACE is a confined space, achieving graft immune tolerance through local immunosuppressive drug delivery is therefore feasible. Here, we show that islet rejection in the ACE of mice can be significantly suppressed through local delivery of rapamycin by carefully designed sustained-release microparticles. In this 30-day study, allogeneic islet grafts with blank microparticles were completely rejected 18 days post-transplantation into mice. Importantly, allogeneic islet grafts co-injected with rapamycin releasing microparticles into a different eye of the same recipient were preserved much longer, with some grafts surviving for more than 30 days. Hence, islet allograft survival was enhanced by a localized and prolonged delivery of an immunosuppressive drug. We envisage that this procedure will relieve diabetic transplant recipients from harsh systemic immune suppression, while achieving improved glycemic control and reduced insulin dependence.

ENZYMATICALLY SYNTHESIZED pH-RESPONSIVE IPN FOR IN-SITU RELEASE OF PANTOPRAZOLE SODIUM

Objective: This study involves the synthesis of Gum tragacanth (gt) based interpenetrating polymer network (ipn) and its utilization for sustained release of anti-ulcerative drug i.e. pantoprazole sodium.
 Methods: IPN was synthesized from Gum tragacanth, polyacrylic acid (gt-cl-paa) hydrogel. gt-cl-paa was kept in distilled water. Further, acryamide (aam) and methylmethacrylate (mma) was added and then kept for overnight. Later on, lipase and glutaraldehyde were added. Homopolymers and the unreacted monomers were removed using acetone. Synthesized IPN was dried at 50 °C for further study.
 Synthesized ipn was swelled in water and the drug was added to it. The drug was entrapped in the pores of the synthesized ipn and then drug release behavior was studied using uv-vis spectrophotometer.
 Results: Gt, paa and mma based crosslinked IPN were synthesized using lipase-glutaraldehyde as initiator-crosslinker system. The synthesized IPN was pH sensitive and possessed the desired swelling capacity required for the controlled and systematic liberation of pantoprazole sodium at 37 °C. The kinetic of drug release was studied and found that lateral diffusion (DL) of drug was higher as compared to the initial diffusion (DI). The prepared IPN can be used as prospective carrier for prolonged drug delivery.
 Conclusion: A novel pH sensitive and colon targeted IPN was synthesized. It acts as an effective device for the controlled release of drug pantoprazole sodium.

COLON SPECIFIC DELIVERY OF COMBINATION OF 5-FLUOROURACIL AND CELECOXIB: PREPARATION, CHARACTERIZATION, AND IN VITRO CYTOTOXICITY ASSAY

Objective: 5-Fluorouracil (5-FU) and celecoxib (Cel) combination offered additive effect in the treatment of colon cancer. However, physicochemical and biopharmaceutical attributes of both drugs deliver suboptimal concentration at the site of action. The objective of the current study is the development of a microparticulate drug delivery system loaded with a combination of 5-FU and Cel to achieve prolonged drug delivery in colon cancer.
 Methods: 5-FU and Cel combination were loaded in Eudragit coated chitosan (CH) microspheres (MSs) and characterized.
 Results: The average particle size of the MSs was in the range of 2.7±0.9μm to 4.8±1.1μm. A substantial drug encapsulation efficiency of 71.30±2.3% as obtained for 5-FU as compared to 35.20±1.9% of Cel in the tailored microparticles. The drug loading capacity of 6.5 mg/10 mg and 2.3 mg/10 mg was obtained for 5-FU and Cel, respectively. By Eudragit S 100 (Ed) coating, significant pH-dependent release profile was achieved, and no drug release was observed in simulated gastric and intestinal fluids. The developed MSs exhibited the release of 92.1±2.9% of 5-FU in 8h whereas 18.9±0.7% Cel was found to be released from the developed MSs. The drug-loaded MSs exhibited appreciable potency against HT-29 cells with an IC50 value of 35.9 μM.
 Conclusion: The results indicated that these microparticles are a promising vehicle for selectively targeting drugs to the colon in the chemotherapy of colon cancer.

Fibrin glue as a local drug-delivery system for bacteriophage PA5

Fibrin glue has been used clinically for decades in a wide variety of surgical specialties and is now being investigated as a medium for local, prolonged drug delivery. Effective local delivery of antibacterial substances is important perioperatively in patients with implanted medical devices or postoperatively for deep wounds. However, prolonged local application of antibiotics is often not possible or simply inadequate. Biofilm formation and antibiotic resistance are also major obstacles to antibacterial therapy. In this paper we test the biocompatibility of bacteriophages incorporated within fibrin glue, track the release of bacteriophages from fibrin scaffolds, and measure the antibacterial activity of released bacteriophages. Fibrin glue polymerized in the presence of the PA5 bacteriophage released high titers of bacteriophages during 11 days of incubation in liquid medium. Released PA5 bacteriophages were effective in killing Pseudomonas aeruginosa PA01. Overall, our results show that fibrin glue can be used for sustained delivery of bacteriophages and this strategy holds promise for many antibacterial applications.

ASSESSMENT OF SELF-EXTRACTED CELLULOSE FROM ORYZA SATIVA FOR DESIGN OF CONTROLLED DRUG DELIVERY SYSTEM OF DALFAMPRIDINE

Objectives: The main objective of the present work includes extraction of cellulose from Oryza sativa (OS), characterization of cellulose, development of controlled release tablet dalfampridine using cellulose of OS, and in vitro evaluation.
 Methods: Dry powdered OS husk sample was extracted with a mixture of hexane and methanol (2:1, v/v) using soxhlation method and was characterized by solubility, melting point determination, differential scanning calorimetry (DSC), and Fourier-transform infrared (FTIR) analysis. Compatibility between dalfampridine and the mixture of cellulose with dalfampridine was confirmed by FTIR and DSC analysis. Then, controlled drug delivery system of dalfampridine were prepared as directly compressed tablets using various compositions containing OS cellulose, hydroxypropyl methylcellulose (HPMC), dicalcium phosphate, and magnesium stearate (8 nos. F1 to f8) and were evaluated.
 Results: Cellulose was extracted from OS extract to possess its ideal characteristics. Dalfampridine and its mixture with cellulose were compatible according to FTIR and DSC analysis. Directly compressed tablets made with 10 mg of dalfampridine and OS cellulose, HPMC, dicalcium phosphate, and magnesium stearate evidenced prolonged and controlled drug delivery of dalfampridine for 12 h. Formulation made with OS cellulose 250 mg, HPMC 20 mg, dicalcium phosphate 40 mg, and magnesium stearate 5 mg was ideal without burst release.
 Conclusion: Cellulose extracted from OS is used successfully for the production of directly compressed tablets of dalfampridine to elicit optimum characteristics including controlled drug delivery for 12 h.

Stealth Iron Oxide Nanoparticles for Organotropic Drug Targeting.

The ability of peculiar iron oxide nanoparticles (IONPs) to evade the immune system was investigated in vivo. The nanomaterial was provided directly into the farming water of zebrafish ( Danio rerio) and the distribution of IONPs and the delivery of oxytetracycline (OTC) was studied evidencing the successful overcoming of the intestinal barrier and the specific and prolonged (28 days) organotropic delivery of OTC to the fish ovary. Noteworthy, no sign of adverse effects was observed. In fish blood, IONPs were able to specifically bind apolipoprotein A1 (Apo A1) and molecular modeling showed the structural analogy between the IONP@Apo A1 nanoconjugate and high-density lipoprotein (HDL). Thus, the preservation of the biological identity of the protein suggests a plausible explanation of the observed overcoming of the intestinal barrier, of the great biocompatibity of the nanomaterial, and of the prolonged drug delivery (benefiting of the lipoprotein transport route). The present study promises novel and unexpected stealth materials in nanomedicine.