Preparation and Evaluation of Irinotecan Poly(Lactic-co-Glycolic Acid) Nanoparticles for Enhanced Anti-tumor Therapy.

Irinotecan (IRT), the pro-drug of SN-38, has exhibited potent cytotoxicity against various tumors. In order to enhance the anti-tumor effect of IRT, we prepared IRT-loaded PLGA nanoparticles (IRT-PLGA-NPs) by emulsion-solvent evaporation method. Firstly, IRT-PLGA-NPs were characterized through drug loading (DL), entrapment efficiency (EE), particle size, zeta potential, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). We next studied the in vitro release characteristics of IRT-PLGA-NPs. Finally, the pharmacokinetics and pharmacodynamics profiles of IRT-PLGA-NPs were investigated. The results revealed that IRT-PLGA-NPs were spherical with an average size of (169.97 ± 6.29) nm and its EE and DL were (52.22 ± 2.41)% and (4.75 ± 0.22)%, respectively. IRT-PLGA-NPs could continuously release drug for 14 days in vitro. In pharmacokinetics studies, for pro-drug IRT, the t1/2ß of IRT-PLGA-NPs was extended from 0.483 to 3.327 h compared with irinotecan solution (IRT-Sol), and for its active metabolite SN-38, the t1/2ß was extended from 1.889 to 4.811 h, which indicated that IRT-PLGA-NPs could prolong the retention times of both IRT and SN-38. The pharmacodynamics results revealed that the tumor doubling time, growth inhibition rate, and specific growth rate of IRT-PLGA-NPs were 2.13-, 1.30-, and 0.47-fold those of IRT-Sol, respectively, which demonstrated that IRT-PLGA-NPs could significantly inhibit the growth of tumor. In summary, IRT-PLGA-NPs, which exhibited excellent therapeutic effect against tumors, might be used as a potential carrier for tumor treatment in clinic.

Use of thermal and non thermal techniques for assessing compatibility between mirtazapine and solid lipids.

The present investigation was aimed at the evaluation of possible interactions between mirtazapine and selected solid lipids that are commonly used to develop solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs). The solids lipids explored were palmitic acid, stearic acid, glycerylmonostearate, cutina CPPH, sterotex NF, gelucire 50/13, hydrogenated castor oil and compritol 888 ATO. The techniques used were Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Hot Stage Microscopy (HSM) and Isothermal Stress Testing (IST) studies. In some cases, the DSC results indicated the possibility of drug-solid lipid interactions which was further ruled out by performing HSM studies. Moreover, IST studies were also used to further confirm the compatibility between the drug and selected solid lipids. And the findings from these studies indicated compatibility between mirtazapine and solid lipids that can further be used to develop SLNs or NLCs.

Development and Evaluation of Stimuli-Responsive Chimeric Nanostructures.

Chimeric/mixed stimuli-responsive nanocarriers are promising agents for therapeutic and diagnostic applications, as well as in the combinatorial field of theranostics. Herein, we designed chimeric nanosystems, composed of natural phospholipid and pH-sensitive amphiphilic diblock copolymer, in different molar ratios and assessed the polymer lyotropic effect on their properties. Initially, polymer-grafted bilayers were evaluated for their thermotropic behavior by thermal analysis. Chimeric liposomes were prepared through thin-film hydration and the obtained vesicles were studied by light scattering techniques, to measure their physicochemical characteristics and colloidal stability, as well as by imaging techniques, to elucidate their global and membrane morphology. Finally, in vitro screening of the systems' toxicity was held. The copolymer effect on the membrane phase transition strongly depended on the pH of the surrounding environment. Chimeric nanoparticles were around and above 100 nm, while electron microscopy revealed occasional morphology diversity, probably affecting the toxicity of the systems. The latter was assessed to be tolerable, while dependent on the nanosystems' material concentration, polymer concentration, and polymer composition. All experiments suggested that the thermodynamic and biophysical properties of the nanosystems are copolymer-composition- and concentration-dependent, since different amounts of incorporated polymer would produce divergent effects on the lyotropic liquid crystal membrane. Certain chimeric systems can be exploited as advanced drug delivery nanosystems, based on their overall promising profiles.

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

Albumin Carriers for Cancer Theranostics: A Conventional Platform with New Promise.

Theranostic nanoplatforms with integrated diagnostic and therapeutic functions, aiming at imaging-guided therapy to improve treatment planning, as well as combination therapy to enhance treatment efficacy, have received tremendous attention in recent years. Among numerous types of functional nanomaterials explored in this field, protein-based nanocarriers with inherent biocompatibility have also been selected as building blocks to construct multifunctional theranostic platforms. In particular, albumin, which has been extensively used as drug-delivery carriers for decades, has shown great new promise in the construction of novel imaging and therapeutic nanoagents, as demonstrated by a number of recent studies. IHere, the motivations of using albumins to build up nanoscale theranostics are discussed, and the latest progress/future perspectives in this direction are summarized.

Probing location of anti-TB drugs loaded in Brij 96 microemulsions using thermoanalytical and photophysical approach.

The aim of this work is to monitor the changes in microstructure in nonionic Brij 96 microemulsions and to locate the solubilization loci of antituberculosis drugs (of variable solubility using photophysical and thermoanalytical properties. Using properties such as spectral shift, Stroke's shift, and anisotropy for two dyes, that is, Nile red (NR) and tris(2,2'-bipyridine)ruthenium(II) dichloride (RC), the structure of microemulsions has been investigated. With the help of spectral and deconvoluted analysis, it has been seen that rifampicin (RIF) shows a strong interaction with NR and isoniazid (INH) and pyrazinamide (PZA) with RC. It has been concluded that RIF molecules are mainly present at the interface toward oil side and INH toward hydrophilic side, whereas PZA remains in free water. The findings have been correlated with aqueous solubility drugs and partition coefficients. Differential scanning calorimetry elucidates the state of water in microheterogeneous environment and variation of different states, that is, free, bound, interphasal, and nonfreezable water with dilution. In addition, it confirmed the stability and location of the drugs in the prepared Brij 96 microemulsion formulations. A good agreement between both the studies has been achieved. These findings will help in elucidating the drug delivery properties of anti-TB drugs-loaded microemulsion formulations in future.

Evaluation of the properties of Gongronema latifolium in phospholipon 90H based solid lipid microparticles (SLMs): an antidiabetic study.

CONTEXT: Gongronema latifolium Benth Hook, (Asclepiadaceae) is a tropical rainforest plant primarily used in traditional folk medicine in the treatment of malaria, diabetes, hypertension, and as laxative. OBJECTIVE: To study the antidiabetic properties of Gongronema latifolium-loaded solid lipid microparticles (SLMs). MATERIALS AND METHODS: The methanolic extract of Gongronema latifolium leaves were obtained and formulated into SLMs using lipid matrix comprising of fat from Capra hircus and Phospholipon® 90H. The SLMs were characterized in vitro by determining the particle size and morphology, pH stability studies, and encapsulation efficiency EE%. Also, the antidiabetic properties of the Gongronema latifolium-loaded SLMs were studied in alloxan-induced diabetic rats. RESULTS AND DISCUSSION: The results show that the particle size of G. latifolium-loaded SLMs was within an acceptable range for SLMs. Highest EE% of 68% was obtained for SLMs containing 5% G. latifolium (batch F3). The formulations remained stable with insignificant pH reduction over time (p < 0.05). Gongronema latifolium-loaded SLMs had mean percentage reduction in blood glucose of 76% at 2 h, 42.3% at 8 h, and 24.4% at 12 h, while the group that received the reference-glibenclamide had 82.6, 61.7, and 46.7% at 2, 8, and 12 h, respectively, after oral administration of all samples. Gongronema latifolium-loaded SLMs had blood glucose reduction significantly higher than the pure extract and the glibenclamide (p < 0.05) at the concentrations used. CONCLUSIONS: Gongronema latifolium-loaded SLMs exhibited a good hypoglycemic effect and could be used for the treatment of diabetes.

Properties and stability of blueberry anthocyanin--bovine serum albumin nanoparticles.

BACKGROUND: Since they would be easily decomposed under alkaline conditions, anthocyanins are likely to have poor oxidation stability. However, encapsulated with protein molecules, anthocyanins could be protected owing to the slowing down of the oxidation process. In this study, the characteristics of nanoparticles, formed by the interactions of anthocyanins with bovine serum albumin (BSA), and their impact on the oxidation stability of anthocyanins were investigated. RESULTS: Both BSA and anthocyanin-bound BSA could form self-assembled nanoparticles in phosphate buffer (pH 7.4), and the particle size of anthocyanin-bound BSA (20-25 nm) was smaller than that of BSA (35-40 nm). The ratio of BSA to anthocyanin was 1:10. The radical scavenging rates of BSA-bound anthocyanin were lower than those of the unbound anthocyanin. No significant difference was seen in the stability between the unbound and BSA-bound anthocyanin in the simulated gastric system, whereas a difference was seen in the simulated intestinal system. The amount of unbound anthocyanin decreased by 70% after 6 h, while BSA-bound anthocyanin was almost unchanged. BSA exhibited a remarkable effect on the oxidation stability of anthocyanins. CONCLUSION: BSA nanocarriers could improve the stability of anthocyanin under neutral conditions, which has great potential for applications.

pH-responsive hydrogels containing PMMA nanoparticles: an analysis of controlled release of a chemotherapeutic conjugate and transport properties.

Biopolymers composed of a pH-responsive, hydrophilic poly(methacrylic acid-grafted-ethylene glycol) network polymerized in the presence of poly(methyl methacrylate) nanoparticles were designed for the oral delivery of chemotherapeutics for the treatment of colon cancer. An inulin-doxorubicin conjugate, designed to target the colon and improve doxorubicin efficacy, was loaded into these polymer carriers at an efficiency of 54%. Release studies indicated these polymer carriers minimized conjugate release in low pH conditions and released the conjugate at neutral pH conditions using a two-step pH experiment modeling the stomach and the small intestine. At lower concentration levels, the presence of the polymer carriers did not disrupt tight junctions as determined by transepithelial electrical resistance studies using Caco-2 and HT29-MTX cell lines which are an accurate model of the GI tract epithelia. Permeability values of unmodified doxorubicin and the inulin-doxorubicin conjugate in the presence of the polymer carriers were also determined using the same cell models and ranged from 1.87 to 3.80 × 10 (-6) cm/s.

Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery.

The purposes of this study were to develop and evaluate calcium pectinate/alginate microspheres (PAMs) and to exploit their pH-sensitive properties for colon-targeted delivery of encapsulated cisplatin. PAMs were prepared using an electrospraying method. The PAMs, as cores, were then coated with Eudragit S100 using a polyelectrolyte multilayer coating technique in aqueous solution. The morphology of the microspheres was observed under scanning electron microscopy. In vitro drug release studies were performed in simulated gastrointestinal fluid, and the results indicated that approximately 5 % of the cisplatin was released from the Eudragit S100-coated PAMs, and 51 % of the cisplatin was released from the uncoated PAMs at 1 h. The release of cisplatin from the Eudragit S100-coated PAMs was more sustained in simulated gastric fluid than in simulated intestinal fluid due to the increased solubility of the coating polymer in media with pH >7.0. Drug release from the Eudragit S100-coated PAMs was best described by the Higuchi's square root model. From these results, it was concluded that Eudragit S100-coated PAMs are a potential carrier for delivery of cisplatin to the colon.

Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation, characterization, and in vitro drug release study.

CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.

Liposome combined porous beta-TCP scaffold: preparation, characterization, and anti-biofilm activity.

The objective of this study was to design a novel artificial bone scaffold for therapy and prevention of refractory bacterial infection. Porous beta-tricalcium phosphate (beta-TCP) scaffold was combined with liposomal gentamicin (GS) to form a novel complex drug carrier. The liposome combined beta-TCP scaffold (LCS) was characterized for its liposome binding rate, drug loading, and micromorphology. The anti-biofilm activity of LCS was evaluated by Staphylococcus aureus biofilm in vitro. The drug release from LCS was recognized as an initial high dose of liposomal GS released from the matrix and a further sustained release of free GS from the liposome, respectively, and it is an ideal release pattern for treatment and prevention of post-operative osteomyelitis. The release kinetics was influenced by variation of particle size of liposome. LCS displayed a potential anti-biofilm activity even in the lowest GS concentration (2.5 microg/mL), and the regrowth time was extended from 5.0 h to 9.5 h. At a higher dosage range, the highest anti-biofilm activity was achieved by LCS with liposomal particle size of 800 nm. In conclusion, the development of LCS showed a new pathway for controlled delivery of liposomal antibiotics for treatment of osteomyelitis caused by persistent bacterial infection.

Cyclodextrins as carriers for kavalactones in aqueous media: spectroscopic characterization of (S)-7,8-dihydrokavain and beta-cyclodextrin inclusion complex.

Kavalactones represent the active constituents of kava-kava (Piper methysticum G. Forster), endowed with sedative and anaesthetic properties. Kavalactones are polar constituents, but poorly soluble in water with a low bioavailability. In this study, the formation of inclusion complexes of one of the most representative kavalactone isolated from kava-kava extract, (S)-7,8-dihydrokavain (DHK), with beta-cyclodextrin (beta-CyD) was investigated mainly by spectroscopic methods. NMR experiments were extensively used for the complete characterization of the complex and included (1)H NMR complexation shifts analysis, (1)H NMR diffusion measurements (DOSY), and ROESY experiments. In particular DOSY experiments demonstrated that in the presence of beta-CyD the translational diffusion of kavalactone is sizably slowed down (2.5x10(-10)m(2)/s) with respect to the free drug (4.4x10(-10)m(2)/s) according to the inclusion of DHK in the cavity of (beta-CyD). ROESY experiments confirmed the inclusion of DHK in the hydrophobic pocket of beta-CyD through the primary hydroxyl rim, being the most relevant interactions between the H3' of beta-CyD and the ortho protons on the phenyl ring of the DHK, and between H5' of beta-CyD and the meta/para protons of DHK phenyl ring. The inclusion of the phenyl ring of DHK, leaving the lactone moiety outside of CyD was also confirmed by the induced CD effects. The binary solution DHK/beta-CyD shows a 50% intensity increase of the negative band of the pi-pi* transitions of the phenyl ring with respect to the absorption observed with DHK alone. Molecular dynamics simulations results corroborated and further clarify observed spectroscopic data. It was found that the phenylethyl substituent at C6 has a preferential equatorial position in the free state, and an axial one in the complex, justifying the large downfield shift experienced by H6 of DHK upon binding. Finally the influence of beta-CyD on water solubility of DHK was investigated by phase-solubility studies. In the range 2-4mM of host, solubility of DHK was increased only two-fold, but being beta-CyD also a penetration enhancer, in vivo studies will be performed to clarify a possible role of the complex on the bioavailability of DHK.

Ammonium sulfate gradient loading of brucine into liposomes: effect of phospholipid composition on entrapment efficiency and physicochemical properties in vitro.

BACKGROUND: Brucine, the major active alkaloid constituent extracted from traditional Chinese herbal medicine Nux vomica, had been found to possess remarkable antitumor, analgesic, and anti-inflammatory activities. In this study, we attempted to encapsulate brucine into liposomes to improve its therapeutic effects. The entrapment efficiency (EE) and the stability of liposomes are two key factors associated with the therapeutic effects of liposomal drugs. We developed a novel liposome-based brucine formulation that was composed of soybean phosphatidylcholine (SPC) and hydrogenated soybean phosphatidylcholine (HSPC). METHOD: The liposomes with different phospholipid composition were characterized for their EE, vesicle size, drug release profile, and leakage in vitro. RESULTS: The molar ratio of HSPC/SPC = 1:9 was determined as the optimum ratio. Compared with conventional liposomes composed of only SPC or HSPC, EE of the brucine-loaded novel liposomes was increased markedly, especially at high drug/lipid molar ratios. The results of drug release showed that the novel liposomes were more stable than the conventional SPC liposomes in the presence of fetal calf serum. In addition, the results of the leakage experiments revealed that the novel liposomes also had better stability in phosphate buffer solution (PBS) with respect to drug retention. Although the conventional HSPC liposomes is more stable than the novel liposomes, the novel liposomes composed of 10% HSPC and 90% SPC may still have promising application potential because HSPC is much more expensive than SPC. CONCLUSION: Taken together, efficient encapsulation of brucine into the novel liposomes, their improved stability, and the price of phospholipids indicate that the novel liposomes may act as promising carriers for active alkaloids such as brucine.

Influence of surface chemistry of mesoporous alumina with wide pore distribution on controlled drug release.

The crucial role of the drug carrier surface chemical moeities on the uptake and in vitro release of drug is discussed here in a systematic manner. Mesoporous alumina with a wide pore size distribution (2-7 nm) functionalized with various hydrophilic and hydrophobic surface chemical groups was employed as the carrier for delivery of the model drug ibuprofen. Surface functionalization with hydrophobic groups resulted in low degree of drug loading (approximately 20%) and fast rate of release (85% over a period of 5 h) whereas hydrophilic groups resulted in a significantly higher drug payloads (21%-45%) and slower rate of release (12%-40% over a period of 5 h). Depending on the chemical moiety, the diffusion controlled ( proportional, varianttime(-)(0.5)) drug release was additionally observed to be dependent on the mode of arrangement of the functional groups on the alumina surface as well as on the pore characteristics of the matrix. For all mesoporous alumina systems the drug dosages were far lower than the maximum recommended therapeutic dosages (MRTD) for oral delivery. We envisage that the present study would aid in the design of delivery systems capable of sustained release of multiple drugs.

Monitoring of release of cargo from nanocarriers by MRI/MR spectroscopy (MRS): significance of T2/T2* effect of iron particles.

To monitor the release of cargo molecules from nanocarriers, a novel MRI/MRS technique was developed and tested. This novel approach uses a simultaneous encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles and either a gadolinium (Gd)-based paramagnetic contrast agent, Gd-diethylenetriamine pentaacetic acid bismethylamide(GdDTPA-BMA), for MRI, or an anticancer agent, 5-fluorouracil (5-FU), for MRS. These agents have significantly different diffusion properties due to their different molecular sizes. Strong negative signal enhancement due to the T(2) effects of SPIO dominates the positive T(1) contrast generated by GdDTPA-BMA when SPIO and GdDTPA-BMA are in close proximity (intact form). Positive T(1) contrast becomes evident upon release of GdDTPA-BMA from the carrier once the distance between GdDTPA-BMA and SPIO molecules is beyond the T(2) enhancement range. Similarly, intact nanocarriers loaded with 5-FU and SPIO have a broad (19)F resonance line because line-width is inversely proportional to T*2, while free 5-FU appears as a narrow resonance line once it is released from the liposomes. This technique allowed monitoring of the release of cargo molecules from liposomes encapsulating both SPIO and either GdDTPA-BMA or 5-FU by MRI/MRS in vitro using 2% agarose gel phantoms. Experimental results demonstrate successful demarcation of the released cargo molecules vs. encapsulated molecules.

Characterization of microemulsion structures in the pseudoternary phase diagram of isopropyl palmitate/water/Brij 97:1-butanol.

This research was aimed to characterize microemulsion systems of isopropyl palmitate (IPP), water, and 2:1 Brij 97 and 1-butanol by different experimental techniques. A pseudoternary phase diagram was constructed using water titration method. At 45% wt/wt surfactant system, microemulsions containing various ratios of water and IPP were prepared and identified by electrical conductivity, viscosity, differential scanning calorimetry (DSC), cryo-field emission scanning electron microscopy (cryo-FESEM) and nuclear magnetic resonance (NMR). The results from conductivity and viscosity suggested a percolation transition from water-in-oil (water/oil) to oil-in-water (oil/water) microemulsions at 30% wt/wt water. From DSC results, the exothermic peak of water and the endothermic peak of IPP indicated that the transition of water/oil to oil/water microemulsions occurred at 30% wt/wt water. Cryo-FESEM photomicrographs revealed globular structures of microemulsions at higher than 15% wt/wt water. In addition, self-diffusion coefficients determined by NMR reflected that the diffusability of water increased at higher than 35% wt/wt water, while that of IPP was in reverse. Therefore, the results from all techniques are in good agreement and indicate that the water/oil and oil/water transition point occurred in the range of 30% to 35% wt/wt water.

Evaluating gelatin based nanoparticles as a carrier system for double stranded oligonucleotides.

PURPOSE: Surface modified gelatin nanoparticles were tested as a potential carrier system for double stranded DNA and RNA oligonucleotides. The results will be discussed with regard to former experiments conducted with single stranded oligonucleotides. METHODS: Gelatin nanoparticles were prepared by a two step desolvation method and surface modified by the covalent coupling of a quaternary amine to obtain a permanent positive net charge. Oligonucleotide loading was conducted in three different media applying 50 microg oligonucleotide per mg nanoparticles in total. Five batches of nanoparticles varying in size and zeta potential (zeta) were tested. The zeta potentials were determined under enforced ionic conditions in a 10 mmol sodium chloride solution at pH 7.0. The separation of unbound oligonucleotides and gelatin nanoparticles was achieved by centrifugation. Free oligonucleotide was determined UV-spectrophotometrically (260 nm) in the supernatant. RESULTS: It could be shown that up to 50 microg nucleic acid per mg nanoparticles can be bound depending on the particle's zeta potential and the chosen incubation medium. CONCLUSIONS: The results suggest that the proposed procedure allows a successful drug loading of double stranded oligonucleotides onto to the surface of accordingly modified gelatin nanoparticles.