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Recent Advances in Non-Invasive Delivery of Macromolecules using Nanoparticulate Carriers System

Shadab M, Haque S, Sheshala R, Meng LW, Meka VS, Ali J

Curr Pharm Des, 2017;23(3):440-453.
PMID: 27784250 DOI: 10.2174/1381612822666161026163201

BACKGROUND: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects.
METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects.
RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles.
CONCLUSION: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.

Matched MeSH terms: Macromolecular Substances/chemistry
Controlled release compound based on metanilate-layered double hydroxide nanohybrid

Hussein MZ, Nasir NM, Yahaya AH

J Nanosci Nanotechnol, 2008 Nov;8(11):5921-8.
PMID: 19198327

Metanilate-layered double hydroxide nanohybrid compound was synthesized for controlled release purposes through co-precipitation method of the metal cations and organic anion. The effect of various divalent metal cations (M2+), namely Zn2+, Mg2+ and Ca2+ on the formation of metanilate-LDH nanohybrids, in which metanilate anion was intercalated into three different layered double hydroxide (LDH) systems; Zn-Al, Mg-Al and Ca-Al were investigated. The syntheses were carried out with M2+ to Al3+ initial molar ratio, R of 4. The pH of the mother liquor was maintained at pH 7.5 and 10 during the synthesis, and the resulting mixture was aged at around 70 degrees C for about 18 h. The intercalation of metanilate anion into the host was found to be strongly influenced by the M2+ that formed the inorganic metal hydroxide layers. Under our experimental condition, the formation of the nanohybrid materials was found to be more feasible for the Zn-Al than for the other two systems, in which the former showed well-ordered layered organic-inorganic nanohybrid structure with good crystallinity. Intercalation is confirmed by the expansion of the interlayer spacing to about 15-17 A when metanilate was introduced into the interlamellae of Zn-Al LDHs. In addition, CHNS and FTIR analyses also support that metanilate anion has been successfully intercalated into the interlamellae of the inorganic LDH. Apart from M2+, this study also shows that the initial pH of the mother liquor plays an important role in determining the physicochemical properties of the resulting nanohybrids, especially the mole fraction of the Zn2+ substituted by the Al3+ ion in the LDH inorganic sheets which in turn controlled the loading percentage of the organic anion, surface properties and the true density. Preliminary study shows that LDH can be used to host beneficial guests, active agent with controlled release capability of the guests. Generally the overall process is governed by pseudo second order kinetic but for the first 180 min, the release process can be slightly better described by parabolic diffusion than the other models.

Matched MeSH terms: Macromolecular Substances/chemistry
Synthesis and characterization of polymeric V2O5/AlO(OH) with nanopores on alumina support

Ahmad AL, Abd Shukor SR, Leo CP

J Nanosci Nanotechnol, 2006 Dec;6(12):3910-4.
PMID: 17256351

Polymeric vanadium pentoxide gel was formed via the reaction of V2O5 powder with hydrogen peroxide. The polymeric vanadium pentoxide gel was then dispersed in alumina gel. Different vanadium loading composites were coated on alumina support and calcined at 500 degrees C for 1 hr. These composite layers were characterized using TGA, FT-IR, XRD, SEM, and Autosorb. It was found that the lamellar structure of polymerized vanadium pentoxide was retained in the inorganic matrix. Crystalline alumina in gamma phase was formed after calcinations. However, the vanadium-alumina mixed oxides are lack of the well defined PXRD peaks for polycrystalline V2O5. This is possibly because the vanadia species are highly dispersed in the alumina matrix or the vanadia species are dispersed as crystalline which is smaller than 4 nm. In addition, the imbedded polymeric vanadium oxide improved the specific area and average pore diameter of the composite layer.

Matched MeSH terms: Macromolecular Substances/chemistry
A facile approach to prepare regenerated cellulose/graphene nanoplatelets nanocomposite using room-temperature ionic liquid

Mahmoudian S, Wahit MU, Imran M, Ismail AF, Balakrishnan H

J Nanosci Nanotechnol, 2012 Jul;12(7):5233-9.
PMID: 22966551

This study presents the preparation of regenerated cellulose (RC)/graphene nanoplatelets (GNPs) nanocomposites via room temperature ionic liquid, 1-ethyl-3-methylimidazolium acetate (EMIMAc) using solution casting method. The thermal stability, gas permeability, water absorption and mechanical properties of the films were studied. The synthesized nanocomposite films were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The T20 decomposition temperature of regenerated cellulose improved with the addition of graphene nanoplatelets up to 5 wt%. The tensile strength and Young's modulus of RC films improved by 34 and 56%, respectively with the addition of 3 wt% GNPs. The nanocomposite films exhibited improved oxygen and carbon dioxide gas barrier properties and water absorption resistance compared to RC. XRD and SEM results showed good interaction between RC and GNPs and well dispersion of graphene nanoplatelets in regenerated cellulose. The FTIR spectra showed that the addition of GNPs in RC did not result in any noticeable change in its chemical structure.

Matched MeSH terms: Macromolecular Substances/chemistry
Substrate effects on surface morphologies and magnetic properties of nanostructured FePt thin films

Low PL, Yong BE, Ong BH, Matsumoto M, Tou TY

J Nanosci Nanotechnol, 2011 Mar;11(3):2640-3.
PMID: 21449444

The substrate effects on surface morphologies, crystal structures, and magnetic properties of the sputter-deposited FePt thin films on Corning 1737, normal glass, and Si wafer substrates, respectively, were investigated. High in-plane coercivities of 10 kOe were obtained for the air-annealed films on Corning 1737 and Si wafer, where both films similarly have granular-like morphologies. Besides, increasing grain size and surface roughness of all the FePt films with the post-anneal temperature were observed. Moreover, partially separated grains were seen in the film on Si wafer, where the formation of Fe silicides during post-anneal is suspected, in which has enhanced the magnetic ordering.

Matched MeSH terms: Macromolecular Substances/chemistry
Observation of a cubical-like microstructure of strontium iron garnet and yttrium iron garnet prepared via sol-gel technique

Nasir N, Yahya N, Kashif M, Daud H, Akhtar MN, Zaid HM, et al.

J Nanosci Nanotechnol, 2011 Mar;11(3):2551-4.
PMID: 21449424

This is our initial response towards preparation of nano-inductors garnet for high operating frequencies strontium iron garnet (Sr3Fe5O12) denoted as SrIG and yttrium iron garnet (Y3Fe5O12) denoted as YIG. The garnet nano crystals were prepared by novel sol-gel technique. The phase and crystal structure of the prepared samples were identified by using X-ray diffraction analysis. SEM images were done to reveal the surface morphology of the samples. Raman spectra was taken for yttrium iron garnet (Y3Fe5O12). The magnetic properties of the samples namely initial permeability (micro), relative loss factor (RLF) and quality factor (Q-Factor) were done by using LCR meter. From the XRD profile, both of the Y3Fe5O12 and Sr3Fe5O12 samples showed single phase garnet and crystallization had completely occurred at 900 degrees C for the SrIG and 950 degrees C for the YIG samples. The YIG sample showed extremely low RLF value (0.0082) and high density 4.623 g/cm3. Interesting however is the high Q factor (20-60) shown by the Sr3Fe5O12 sample from 20-100 MHz. This high performance magnetic property is attributed to the homogenous and cubical-like microstructure. The YIG particles were used as magnetic feeder for EM transmitter. It was observed that YIG magnetic feeder with the EM transmitter gave 39% higher magnetic field than without YIG magnetic feeder.

Matched MeSH terms: Macromolecular Substances/chemistry
Fulltext Conventional study on novel dicationic ionic liquid inclusion with β-cyclodextrin

Mohamad S, Surikumaran H, Raoov M, Marimuthu T, Chandrasekaram K, Subramaniam P

Int J Mol Sci, 2011;12(9):6329-45.
PMID: 22016662 DOI: 10.3390/ijms12096329

This study focuses on the synthesis and characterization of the inclusion complex of β-Cyclodextrin (β-CD) with dicationic ionic liquid, 3,3'-(1,4-Phenylenebis [methylene]) bis(1-methyl-1H-imidazol-3-ium) di(bromide) (PhenmimBr). The inclusion complex was prepared at room temperature utilizing conventional kneading technique. Proton ((1)H) NMR and 2D ((1)H-(1)H) COSY NMR were the primary characterization tools employed to verify the formation of the inclusion complex. COSY spectra showed strong correlations between protons of imidazolium and protons of β-CD which indicates that the imidazolium ring of PhenmimBr has entered the cavity of β-CD. UV absorption indicated that β-CD reacts with PhenmimBr to form a 2:1 β-CD-PhenmimBr complex with an apparent formation constant of 2.61 × 10(5) mol&(-2) L(2). Other characterization studies such as UV, FT-IR, XRD, TGA, DSC and SEM studies were also used to further support the formation of the β-CD-PhenmimBr inclusion complex.

Matched MeSH terms: Macromolecular Substances/chemistry*
Biosynthesis and mobilization of poly(3-hydroxybutyrate) [P(3HB)] by Spirulina platensis

Jau MH, Yew SP, Toh PS, Chong AS, Chu WL, Phang SM, et al.

Int J Biol Macromol, 2005 Aug;36(3):144-51.
PMID: 16005060

Three strains of Spirulina platensis isolated from different locations showed capability of synthesizing poly(3-hydroxybutyrate) [P(3HB)] under nitrogen-starved conditions with a maximum accumulation of up to 10 wt.% of the cell dry weight (CDW) under mixotrophic culture conditions. Intracellular degradation (mobilization) of P(3HB) granules by S. platensis was initiated by the restoration of nitrogen source. This mobilization process was affected by both illumination and culture pH. The mobilization of P(3HB) was better under illumination (80% degradation) than in dark conditions (40% degradation) over a period of 4 days. Alkaline conditions (pH 10-11) were optimal for both biosynthesis and mobilization of P(3HB) at which 90% of the accumulated P(3HB) was mobilized. Transmission electron microscopy (TEM) revealed that the mobilization of P(3HB) involved changes in granule quantity and morphology. The P(3HB) granules became irregular in shape and the boundary region was less defined. In contrast to bacteria, in S. platensis the intracellular mobilization of P(3HB) seems to be faster than the biosynthesis process. This is because in cyanobacteria chlorosis delays the P(3HB) accumulation process.

Matched MeSH terms: Macromolecular Substances/chemistry
Studies on the interaction of mononuclear metal(II) complexes of amino‑naphthoquinone with bio-macromolecules

Kosiha A, Lo KM, Parthiban C, Elango KP

Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:778-787.
PMID: 30423764 DOI: 10.1016/j.msec.2018.10.021

Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {L = 2‑chloro‑3‑((3‑dimethylamino)propylamino)naphthalene‑1,4‑dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104 M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22 × 105 M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22 μM, respectively.

Matched MeSH terms: Macromolecular Substances/chemistry*
Dynamics of PEGylated-dextran-spermine nanoparticles for gene delivery to leukemic cells

Amini R, Jalilian FA, Abdullah S, Veerakumarasivam A, Hosseinkhani H, Abdulamir AS, et al.

Appl Biochem Biotechnol, 2013 Jun;170(4):841-53.
PMID: 23615733 DOI: 10.1007/s12010-013-0224-0

Leukemic cells are hard-to-transfect cell lines. Many transfection reagents which can provide high gene transfer efficiency in common adherent cell lines are not effective to transfect established blood cell lines or primary leukemic cells. This study aims to examine a new class of cationic polymer non-viral vector, PEGylated-dextran-spermine (PEG-D-SPM), to determine its ability to transfect the leukemic cells. Here, the optimal conditions of the complex preparation (PEG-D-SPM/plasmid DNA (pDNA)) were examined. Different weight-mixing (w/w) ratios of PEG-D-SPM/pDNA complex were prepared to obtain an ideal mixing ratio to protect encapsulated pDNA from DNase degradation and to determine the optimal transfection efficiency of the complex. Strong complexation between polymer and pDNA in agarose gel electrophoresis and protection of pDNA from DNase were detected at ratios from 25 to 15. Highest gene expression was detected at w/w ratio of 18 in HL60 and K562 cells. However, gene expression from both leukemic cell lines was lower than the control MCF-7 cells. The cytotoxicity of PEG-D-SPM/pDNA complex at the most optimal mixing ratios was tested in HL60 and K562 cells using MTS assay and the results showed that the PEG-D-SPM/pDNA complex had no cytotoxic effect on these cell lines. Spherical shape and nano-nature of PEG-D-SPM/pDNA complex at ratio 18 was observed using transmission electron microscopy. As PEG-D-SPM showed modest transfection efficiency in the leukemic cell lines, we conclude that further work is needed to improve the delivery efficiency of the PEG-D-SPM.

Matched MeSH terms: Macromolecular Substances/chemistry