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Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy. [ABSTRACT FROM AUTHOR]

Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.

Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge. Nanoparticle-based drug delivery systems offer a potential therapeutic strategy; however, the low loading efficiency, non-responsiveness, and single effect of conventional nanoparticles hinder their clinical application. In this study, we designed a novel self-assembled, dual responsive, and dual drug-loading nanocarrier system, which comprised two parts: the hydrophobic lipid core formed by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG) loaded with alpha-lipoic acid (ALA); and a hydrophilic shell comprising a poly (amidoamine) dendrimer (PAMAM) that electrostatically adsorbed minocycline hydrochloride (Mino). This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment. In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions, and ameliorated periodontal bone resorption. This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.

Magnetic nanoparticles (MNPs) have been identified as promising tools with potential use in a wide range of areas, spreading from diagnostics to the treatment of diseases. The high magnetization value and ability to pass cellular barriers promote them to be used as magnetic resonance imaging (MRI) agents, gene delivery agents, hyperthermia therapy, and for tissue repair. Use of functionalized MNPs with macromolecules minimizes their risks in biological systems and offers organ specific diagnosis and therapy. MNPs functionalized with dendrimers can have better potential in terms of enhanced stability and dispersibility in aqueous solution. The particular review summarizes the recent advances in synthesis of dendrimer functionalized MNPs and their applications in biomedical field such as targeted drug delivery, MRI, magnetic hyperthermia treatment and as antimicrobial agent. [ABSTRACT FROM AUTHOR]

We present the synthesis of polymeric amino- and guanidinoglycosides prepared by tethering neomycin and guanidinoneomycin to PAMAM dendrimers of generations 2 and 4. The ability of these conjugates to promote cellular uptake of high-molecular-weight cargo is discussed, together with their cytotoxicity and mechanisms of entry. We demonstrate that the presence of multiple guanidinoneomycin carriers on the PAMAM surface plays an important role in promoting cellular uptake of the dendrimers, maintaining the heparan sulfate specificity and negligible cytotoxicity typical of monomeric guanidinoglycoside molecular transporters.

Dendrimers are novel three dimensional, hyperbranched globular nano polymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index and excellent control over molecular structure afford dendrimers with ideal drug delivery ability through encapsulating drugs in their interior or covalently conjugating drugs on their surfaces. The adaptable surface functionalization ability enables covalent conjugation of various targeting molecules onto the surface of dendrimers, thereby allowing for generation of various multifunctional nanodevices for targeted drug delivery applications. Drug delivery researchers are especially enthusiastic about possible utility of dendrimers as drug delivery tool. However, to get the maximum benefits of these novel class macromolecules, a research by collaboration is very much essential. Finally, it is one of the youngest and exciting fields of polymer researches where all branches of science can take part and hence, deserves more intensive attention. [ABSTRACT FROM AUTHOR]

Denderimer-modified magnetic nanoparticles are a promising drug delivery nanosystem which can improve the therapeutic efficacy of chemotherapy drugs and can also be beneficial as magnetic resonance (MR) images contrast agent. The present study introduces the preparation and characterization of the potential therapeutic efficiency of curcumin (CUR)-loaded denderimer-modified citric acid coated Fe3O4 NPs. Polyamidoamine (PAMAM, generation G5) was used to encapsulate citric acid coated Fe3O4 nanoparticles. The successful preparation of CUR-loaded nanocarriers were confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. The loading capacity and encapsulation efficiency of CUR molecules were 12 ± 0.03% and 45.58 ± 0.41%, respectively. The anticancer effect of void CUR and CUR-loaded nanocarriers were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on treated MCF-7 cell line. It can be concluded that application of nanoparticles can be more effective strategy for controlled and slow release of CUR in human breast cancer treatment. [ABSTRACT FROM AUTHOR]

In recent years, functional nanomaterials have found an appreciable place in the understanding and treatment of cancer. This work demonstrates the fabrication and characterization of a new class of cationic, biocompatible, peptide dendrimers, which were then used for stabilizing and functionalizing magnetite nanoparticles for combinatorial therapy of cancer. The synthesized peptide dendrimers have an edge over the widely used PAMAM dendrimers due to better biocompatibility and negligible cytotoxicity of their degradation products. The surface engineering efficacy of the peptide dendrimers and their potential use as drug carriers were compared with their PAMAM counterparts. The peptide dendrimer was found to be as efficient as PAMAM dendrimers in its drug-carrying capacity, while its drug release profiles substantially exceeded those of PAMAM’s. A dose-dependent study was carried out to assess their half maximal inhibitory concentration (IC 50 ) in vitro with various cancer cell lines. A cervical cancer cell line that was incubated with these dendritic nanoparticles was exposed to alternating current magnetic field (ACMF) to investigate the effect of elevated temperatures on the live cell population. The DOX-loaded formulations, in combination with the ACMF, were also assessed for their synergistic effects on the cancer cells for combinatorial therapy. The results established the peptide dendrimer as an efficient alternative to PAMAM, which can be used successfully in biomedical applications. [ABSTRACT FROM AUTHOR]

Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer ( APTAS1411) as a therapeutic strategy. The polyamidoamine ( PAMAM)-polyethylene glycol ( PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy ( AFM) and Fourier transform infrared spectroscopy ( FTIR) .In this study, we show that the conjugated PAMAM- PEG- APTAS1411complex dramatically increased PAMAM- PEG-5- FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5- FU- APTAS1411 complex, by thin layer chromatography ( TLC), and an increase in 5-fluorouracil (5- FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5- FU to MKN45 gastric cancer cells in consistent and without toxic effects. [ABSTRACT FROM AUTHOR]

Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.

Green tea polyphenols have attracted significant interest due to their promising therapeutic potential as antitumor agents. These include catechins that have been explored for various tumors with minimal side effects. This paper demonstrates the fabrication and characterization of dendrimerized magnetic nanoparticles, as delivery vectors for epigallocatechin gallate (EGCG). Glutamic acid-functionalized iron oxide nanoparticles (Glu–Fe3O4) were synthesized and modified with the polyethylene glycol polyamidoamine dendrimers of generations 3, 5, and 6. Nanoparticles were characterized by X-ray diffraction, electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. In aqueous colloidal suspensions, they showed a rapid temperature increase under varying magnetic fields, suggesting their potential in chemothermal therapeutic applications. The loading efficiency of the dendrimerized nanoparticles was calculated to be 32.7%, 51.1%, and 56.4% for generations 3, 5, and 6, respectively. In acidic environments, a sustained drug release profile with an increasing but incomplete release was observed. Importantly, EGCG-loaded nanoparticles induced controlled cell death in human cervical cancer cells, demonstrating a 40% reduction in cell population over 24 h at the highest concentration used, with a linear dose-response. [ABSTRACT FROM AUTHOR]

Short circulation is a disadvantage of dendrimers as drug delivery carriers due to their small size. In this work, pH-sensitive morpholino-terminated generation 5 poly(amido amine) (PAMAM) is prepared. At neutral pH, the dendrimer has a hydrophilic neutral surface and thereby stealth property. Under tumor acidic environments, the dendrimer develops positive charges due to protonation of the morpholino groups, and cellular uptake of the dendrimer is subsequently enhanced. The dendrimer is predicted to penetrate deeper within the tumor due to its small size (∼9 nm), and thereby the pH-sensitive function can be efficiently achieved because the microenvironment in the deeper sites is more acidic. Moreover, the morpholino-terminated PAMAM exhibited longer in vivo circulation time compared to PAMAM and hydroxyl-terminated PAMAM, partly compensating for the disadvantage of short circulation of dendrimers. Furthermore, the morpholino-terminated PAMAM also showed lower cytotoxicity than PAMAM and hydroxyl-terminated PAMAM. [ABSTRACT FROM AUTHOR]

[Display omitted] Dendrimers are synthetic nano-molecules with spherical structure and a stardust topology. They have an amphiphilic nature and a hollow structure, with different layers over their central core structure representing each generation. Numerous drugs can be incorporated into the cavity present which helps solve a variety of problems experienced in the delivery of drugs such as poor solubility. Nowadays, dendrimers are being employed for chemotherapeutic drug delivery. The most common cancer worldwide is lung cancer which is caused due to various reasons, the major one being smoking. Dendrimers are presently utilised for the delivery of drugs to various targets and are proved to be successful in treating cancer, with their efficiency to treat lung cancer at various stages is being assessed. Although many nanoparticles (NPs) are available for their medical applications, from diagnosis to cancer treatment, dendrimers succeed amongst all due to most potential in terms of their structure, ability to provide good bioavailability and better stability than other NPs. There are mainly-three types of dendrimers used in treating lung cancer- PAMAM, PLL and PPI dendrimers. This review aims to describe the various properties of the dendrimers, investigate the properties of their various types and discover the reasons for their employment in treatment of lung cancer, the novelty being brought in them and the alterations which make them a potential chemotherapeutic drug delivery system. [ABSTRACT FROM AUTHOR]

The association of the anti-tuberculosis drug rifampicin (RIF) with a 4th-generation poly(amidoamine) (G4-PAMAM) dendrimer was investigated by means of molecular dynamics simulations. The RIF load capacity was estimated to be around 20 RIF per G4-PAMAM at neutral pH. The complex formed by 20 RIF molecules and the dendrimer (RIF 20 -PAMAM) was subjected to 100 ns molecular dynamics (MD) simulations at two different pH conditions (neutral and acidic). The complex was found to be significantly more stable in the simulation at neutral pH compared to the simulation at low pH in which the RIF molecules were rapidly and almost simultaneously expelled to the solvent bulk. The high stability of the RIF-PAMAM complex under physiological pH and the rapid release of RIF molecules under acidic medium provide an interesting switch for drug targeting since the Mycobacterium resides within acidic domains of the macrophage. Altogether, these results suggest that, at least in terms of stability and pH-dependent release, PAMAM-like dendrimers may be considered suitable drug delivery systems for RIF and derivatives. [ABSTRACT FROM AUTHOR]

Abstract: Dendrimers are novel three dimensional, hyperbranched globular nanopolymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery and cavities in the interior distinguish them amongst the available polymers. Applications of dendrimers in a large variety of fields have been explored. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Terminal functionalities provide a platform for conjugation of the drug and targeting moieties. In addition, these peripheral functional groups can be employed to tailor-make the properties of dendrimers, enhancing their versatility. The present review highlights the contribution of dendrimers in the field of nanotechnology with intent to aid the researchers in exploring dendrimers in the field of drug delivery. [Copyright &y& Elsevier]

Highlights: [•] The drug delivery system based on chitosan conjugated PAMAM were prepared. [•] The CS-PAMAM shows lower in vitro cytotoxicity. [•] The anticancer activities of the conjugates of methotrexate–CS-PAMAM were significantly enhanced. [ABSTRACT FROM AUTHOR]

Abstract: The formation of particulate systems with well-defined sizes and shapes is of eminent interest in certain medical applications such as drug delivery, gene transfection, and imaging. The high level of control possible over the architectural design of dendrimers; their size, shape, branching length/density, and their surface functionality, clearly distinguishes these structures as unique and optimum carriers in those applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. In this regard, the high density of exo-presented surface groups allows attachment of targeting groups or functionality that may modify the solution behavior or toxicity of dendrimers. Quite remarkably, modified dendrimers have been shown to act as nano-drugs against tumors, bacteria, and viruses. Recent successes in simplifying and optimizing the synthesis of dendrimers such as the ‘lego’ and ‘click’ approaches, provide a large variety of structures while at the same time reducing the cost of their production. The reflections on biomedical applications of dendrimers given in this review clearly demonstrate the potential of this new fourth major class of polymer architecture and indeed substantiate the high hopes for the future of dendrimers. [Copyright &y& Elsevier]

Abstract: In this paper, the properties of the complete degradation process of newly synthesized multi-block 2.0 G-polyamidoamine-double bond (PAMAM-DB) and resoluble poly (ethylene glycol) -co- poly (glycolic acid) -co- methacryloyl chloride (PEG-co-PGA-co-DB, 4KG5-DB) macromonomers were reported. Rectangular shaped samples were prepared by crosslinking the components using both chemical and photo initiators and exposure to UV light. The aims of the study were to examine the effects of the vitro degradation and drug delivery of the crosslinking group on the properties of photocrosslinked hydrogels. The experimental variable was PAMAM-DB: 4KG5-DB ratio. The effects of this variable on local PH, water uptake, mass loss, and drug release were explored. Polymers were characterized by 1H NMR, 13C NMR, FT-IR, and SEM. Our study revealed that polymers with 40%, 50%, 60% 4KG5-DB (mass fraction) showed more excellent mechanical properties, 40% also showed outstanding vitro degradation properties. In vitro drug release, however, 60% drug released mechanism seemed to approach the Fickian diffusion and possessed more excellent drug release properties compared with formulation 40% and 50%. In general, an increase ratio of 4KG5-DB led to a higher density of tree-like polymer which resulted in slower of degradation and drug release. Incorporation of 4KG5-DB into the polymer was critical for maintaining integrity and increasing hydrophilicity during degradation. These results obtained suggest that this system could be potential as a material for bone replacement and controlled delivery of drugs. [Copyright &y& Elsevier]

Abstract: Dendrimers are an emerging class of nanoscale intracellular drug delivery vehicles. Methylprednisolone (MP) is an important corticosteroid used in the treatment (through inhalation) of lung inflammation associated with asthma. The ability of MP–polyamidoamine (PAMAM) dendrimer conjugate to improve the airway delivery was evaluated in a pulmonary inflammatory murine model that was based on an 11-fold enhancement of eosinophil lung accumulation following five daily inhalation exposures of sensitized mice to the experimental allergen, ovalbumin. MP was successfully conjugated to PAMAM-G4-OH dendrimer yielding 12 MP molecules per dendrimer, and further solubilized in lysine carrier. Five daily trans-nasal treatments with the carrier alone, free MP, and MP–dendrimer at 5mgkg−1 (on a drug basis) did not induce additional lung inflammation, although free MP decreased baseline phagocytic cell recoveries by airway lavage and tissue collagenase dispersion. MP treatments alone decreased ovalbumin-associated airway and tissue eosinophil recoveries by 71 and 47%, respectively. Equivalent daily MP dosing with MP–dendrimer conjugate further diminished these values, with decreases of 87% and 67%, respectively. These findings demonstrate that conjugation of MP with a dendrimer enhances the ability of MP to decrease allergen-induced inflammation, perhaps by improving drug residence time in the lung. This is supported by the fact that only 24% of a single dose of dendrimer delivered to the peripheral lung is lost over a 3-day period. Therefore, conjugation of drugs to a dendrimer may provide an improved method for retaining drugs within the lung when treating such inflammatory disorders as asthma. [Copyright &y& Elsevier]

Abstract: Dendrimers are emerging as potential intracellular drug delivery vehicles. Understanding and improving the cellular efficacy of dendrimer–drug conjugates, can lead to significant in vivo benefits. This study explores efficacy of anionic polyamidoamine (PAMAM–COOH) dendrimer–N-acetyl cysteine (NAC) conjugates for applications in neuroinflammation. The anti-oxidative and anti-inflammatory effects of PAMAM–(COOH)46–(NAC)18 conjugate is evaluated on microglial cells in vitro. Cell entry and localization of PAMAM–(COOH)62–(FITC)2 conjugate in BV-2 microglial cells were assessed using flow cytometry and confocal microscopy. ELISA assays were used to evaluate markers of oxidative stress (ROS, NO) and inflammation (TNF-α) after stimulation of microglial cells with lipopolysaccharides (LPS), following treatment with increasing doses of free N-acetyl-l-cysteine (NAC) or PAMAM–(COOH)46–(NAC)18 conjugate containing an equivalent molar concentration of NAC. Flow cytometry and confocal microscopy demonstrated the PAMAM–(COOH)62–(FITC)2 conjugate entered BV-2 cells rapidly with significant increase in fluorescence within 15min and localized mostly in the cytoplasm. PAMAM–(COOH)46–(NAC)18 conjugate was non-toxic, and significantly reduced ROS, NO and TNF-α release by activated microglial cells after 24h and 72h stimulation of LPS following 3h pre-treatment when compared to the same concentration of free NAC (P <0.05 or P <0.01). Anionic PAMAM dendrimer–NAC conjugate was synthesized with a glutathione sensitive linker for intracellular release. The non-toxic conjugate is a more effective anti-oxidant and anti-inflammatory agent when compared to free NAC in vitro. The conjugate showed significant efficacy even at the lowest dose (0.5mM NAC), where the activity was comparable or better than that of free drug at 8mM (16× higher dosage). The improved efficacy of the conjugate, when combined with the intrinsic neuroinflammation-targeting ability of the PAMAM dendrimers, may provide new opportunities for in vivo applications. [Copyright &y& Elsevier]

Abstract: The interactions of phenobarbital with different generations of amine-terminated poly(amidoamine) (PAMAM) dendrimers were investigated by using two dimensional-nuclear Overhauser effect spectroscopic (2D-NOESY) investigations. The NOESY spectra clearly showed that there were cross-peaks from NOE interactions between the protons of phenobarbital and the protons in interior cavities of generation 5 or generation 6 PAMAM dendrimers but none of such cross-peaks was found in the case of generation 3 or generation 4 dendrimers. The NOESY analysis, together with aqueous solubility data, suggested that higher generation dendrimers are more capable of encapsulating phenobarbital molecules into the interior cavities than lower generation dendrimers, and that lower generation dendrimers are much easier for the electrostatic attachment of phenobarbital molecules than higher ones at a fixed mass concentration. [Copyright &y& Elsevier]

In this study, the distribution of labeled dendrimers in native and aneurysmal rat aortic tissue was examined. Adult male rats underwent infrarenal aorta perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers for varying lengths of time. In a second set of experiments, rats underwent aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later. Aortic diameters were measured prior to and postelastase perfusion, and again on the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed, and mounted. Native aortas were harvested and viewed as negative controls. Aortic cross-sections were viewed and imaged using confocal microscopy. Dendrimers were quantified (counts/high-powered field). Results were evaluated by repeated measures ANOVA and Student's t-test. We found that in native aortas, dendrimers penetrated the aortic wall in all groups. For all perfusion times, fewer dendrimers were present as time between dendrimer perfusion and aortic harvest increased. Longer perfusion times resulted in increased diffusion of dendrimers throughout the aortic wall. By 24 h, the majority of the dendrimers were through the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion, diffused farther into the aortic wall than controls. In conclusion, this study documents labeled dendrimers delivered intra-arterially to native rat aortas in vivo, and the temporal diffusion of these molecules within the aortic wall. Increasing perfusion time and length of time prior to harvest resulted in continued dendrimer diffusion into the aortic wall. These preliminary data provide a novel mechanism whereby local inhibitory therapy may be delivered locally to aortic tissue. [ABSTRACT FROM AUTHOR]

Abstract: The formation of particulate systems with well-defined sizes and shapes is of eminent interest in certain medical applications such as drug delivery, gene transfection, and imaging. The high level of control possible over the architectural design of dendrimers; their size, shape, branching length/density, and their surface functionality, clearly distinguishes these structures as unique and optimum carriers in those applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material and its therapeutic applications. In this regard, the high density of exo-presented surface groups allows attachment of targeting groups or functionality that may modify the solution behavior or toxicity of dendrimers. Quite remarkably, modified dendrimers have been shown to act as nano-drugs against tumors, bacteria, and viruses. Recent successes in simplifying and optimizing the synthesis of dendrimers such as the ‘lego’ and ‘click’ approaches, provide a large variety of structures while at the same time reducing the cost of their production. The reflections on biomedical applications of dendrimers given in this review clearly demonstrate the potential of this new fourth major class of polymer architecture and indeed substantiate the high hopes for the future of dendrimers. [Copyright &y& Elsevier]

This paper describes the synthesis of three neutral water soluble poly(amidoamine) (PAMAM) dendrimer derivatives. The ability of the two larger dendrimers to bind small acidic hydrophobic molecules is reported. Spectroscopic data and pH behaviour suggested that the acidic hydrophobes were forming stable ion pairs with the dendrimer''s internal, basic tertiary nitrogens. With respect to forming 1:1 and 2:1 substrate/dendrimer complexes, both of the larger dendrimers were equally efficient at binding. All dendrimer/substrate complexes were completely miscible with water in all proportions (i.e. infinitely water soluble). When the bound substrates are drug moieties, then the resulting complexes could be considered as potential drug delivery systems. Flow calorimetry demonstrated that the dendrimers were able to release their hydrophobic guests when in contact with a biological cell. [Copyright &y& Elsevier]

The objective of this study was to investigate the influence of physiochemical parameters (such as size, molecular weight, molecular geometry, and number of surface amine groups) of poly (amidoamine) (PAMAM) dendrimers, on their permeability across Caco-2 cell monolayers. The permeability of a series of PAMAM dendrimers, generations 0–4 (G0–G4), was investigated across Caco-2 cell monolayers in both the apical to basolateral (AB) and basolateral to apical (BA) directions. The influence of PAMAM dendrimers on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers was also monitored by measuring the transepithelial electrical resistance (TEER), mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. G0, G1 and G2 demonstrated similar AB permeabilities, which were moderate several fold higher than the AB permeability of higher generations. The AB and BA permeability of G0–G4 typically increased with the increase in donor concentration and incubation time. Permeability values are not reported at generations, concentrations or incubation times that the dendrimers were toxic to Caco-2 cells. TEER values decreased and mannitol permeability increased as a function of donor concentration, incubation time, and generation number. LDH results for G3 and G4 indicate that Caco-2 cell viability was reduced with increasing donor concentration, incubation time, and generation number. The appreciable permeability of G0–G2, coupled with their nontoxic effects on Caco-2 cells, suggest their potential as water-soluble polymeric drug carriers for controlled oral drug delivery. [Copyright &y& Elsevier]

• Modifying gelatin in order to employ non-toxic crosslinker. • Synthesizing injectable and macroporous hydrogel with interconnected pores. • Using two type of nanoparticles for improving mechanical properties. • Reaching a sustainable release of betamethasone sodium phosphate from nanoparticles. Drug delivery systems have been employed to increase efficiency of scaffolds designed for tissue engineering targets, especially remediating an injury. One step even further is utilizing injectable materials to eliminate the need for a second injury in a less invasive manner. The aim of this study is preparation and evaluation of preformed injectable cryogel to overcome fluid leakage of in situ formed hydrogels. For this reason, gelatin was chosen as the main component to resemble the natural extracellular matrix. When it comes to drug nomination, betamethasone sodium phosphate was chosen since severe inflammation response is one of the main reasons for prolong healing. For drug delivery part, two different carriers namely cellulose nanocrystal (CNC) and polyamidoamine (PAMAM) dendrimer were used. It was hypothesized that these nanocarriers not only provide a sustained release of the drug but also boost up mechanical properties. Therefore, prepared samples were characterized chemically, physically and biologically. Based on the results, highly branched nanocarrier (i.e. PAMAM) showed better behavior in mechanical properties (E = 14 kPa) and drug delivery (loading efficiency = 70% and sustain release in 24 h) rather than nanorod carrier (i.e. CNC) with E = 11 kPa and 65% loading efficiency. However, both nanocarriers significantly decrease the rate of degradation almost two times. It seems likely the above mentioned properties as well as the advantage of high cell viability (99% and 105% for CNC and PAMAM incorporated samples respectively) makes the prepared samples a useful alternatives for minimally invasive drug delivery as a tool for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named 'starburst polymers'. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned. [ABSTRACT FROM AUTHOR]