Current Drug Delivery - Volume 15, Issue 4, 2018

Lectins are proteins / glycoproteins of non-immunological origin found ubiquitously in all organisms. Research investigations show that many types of diseased tissues often display glycans that vary from their normal counterparts. Therefore, lectins that can interact with these transformed glycans may be used for early diagnosis and treatment of diseases. Specificity of lectins towards glycans has greatly attracted nanobiotechnology in engineering lectin functionalized nanoparticles. Conjugating lectin with a nanosystem can identify and specifically attach to the carbohydrate moieties of glycoproteins expressed on cell surfaces and this has led to the development of several lectin functionalized nanoparticles to target drugs to various tissues with minimized systemic side effects. Such efficient lectin functionalized nanoparticles developed so far, and their role in targeted drug delivery, targeted therapies and oral immunization are reviewed. Technical difficulties behind designing and targeting these lectin functionalized nanoparticles are also discussed.

Background: The incidence of diabetes mellitus has increased drastically over the past few decades. This oxidant-antioxidant imbalance resulting in complication of diabetes mellitus includes macro- and microvascular complications. Resistance to conventional treatment and patient compliance has paved the way to the usage of effective natural products and supplements. Momordica charantia (bitter gourd) is widely consumed in many parts of Malaysia as a vegetable. Momordica charantia (MC) is mainly used in the management of diabetes mellitus. Objective: The present review discusses the literature concerning the antidiabetic and antioxidant properties of MC focusing on the complication of diabetes mellitus along with its mode of delivery. We found that among the whole part of MC, its fruit extract has been widely studied, therapeutically. The evidence based analysis of the beneficiary effects of MC on the different organs involved in diabetes complication is also highlighted. This review elucidated an essential understanding of MC based drug delivery system in both clinical and experimental studies and appraised the great potential of the protein based MC extract against diabetes mellitus. Conclusion: The review paper is believed to assist the researchers and medical personnel in treating diabetic associated complications.

Intranasal drug delivery system provides distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for the treatment of central nervous system diseases is, low concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantages like improved bioavailability, law dose and quick onset of action and high patient compliance, and the major disadvantage is residence time of drug and irreversible entrapment of drug. This article provides anatomical and physiological information about nasal route and various factors. Article discusses various types of nanoparticles used intranasally and moreover article also emphasizes patents, formulation under development and some.

Background: Until recently, one of the main reasons for mortality has been infectious diseases, and bacteria that are drug-resistant have emerged as a result of the wide application, as well as the misuse of antibacterial medications. Having multidrug-resistance, bacteria present a great problem for the efficient management of bacterial infections and this challenge has resulted in the creation of other means of dealing with bacterial diseases. Of late, metallic nanoparticles (NPs), employed as antibacterial agents, have the potential for use against resistance to bacterial drugs. Objective: The mechanisms of bacterial resistance are described in this review and this is followed by an outline of the features and uses of metallic NPs as antibiotic agents to address bacteria that are antibiotic- sensitive and resistant. Additionally, a general impression of metallic NPs as antibiofilm bactericidal agents is presented. Conclusion: Biofilms and bacterial strains that are resistant to antibiotics present a grave public health challenge and this has enhanced the need to develop new bactericidal agents. Therefore, nanomaterials are considered as a potential platform for managing bacterial infections.

Background: Delivery of conventional small molecule drugs and currently evolving nucleic acid-based therapeutics, such as small interfering RNAs (siRNAs) and genes, and contrast agents for high resolution imaging, to the target site of action is highly demanding to increase the therapeutic and imaging efficacy while minimizing the off-target effects of the delivered molecules, as well as develop novel therapeutic and imaging approaches. Methods: We have undertaken a structured search for peer-reviewed research and review articles predominantly indexed in PubMed focusing on the organic-inorganic hybrid nanoparticles with evidence of their potent roles in intracellular delivery of therapeutic and imaging agents in different animal models. Results: Organic-inorganic hybrid nanoparticles offer a number of advantages by combining the unique properties of the organic and inorganic counterparts, thus improving the pharmacokinetic behavior and targetability of drugs and contrast agents, and conferring the exclusive optical and magnetic properties for both therapeutic and imaging purposes. Different polymers, lipids, dendrimers, peptides, cell membranes, and small organic molecules are attached via covalent or non-covalent interactions with diverse inorganic nanoparticles of gold, mesoporous silica, magnetic iron oxide, carbon nanotubes and quantum dots for efficient drug delivery and imaging purposes. Conclusion: We have thus highlighted here the progress made so far in utilizing different organicinorganic hybrid nanoparticles for in vivo delivery of anti-cancer drugs, siRNA, genes and imaging agents.

Background: Cancer was and still a very stressful and urgent disease condition representing a leading cause of death in developed as well as developing countries. Although, much research work in both medical and pharmaceutical fields has evolved in the past few years in addition to some promising clinical trials and few market products, cancer becomes much wilder, threatening and getting more lives. Most approaches have focused on the synthesis of new active ingredients or chemical modification of available ones, formulating them in suitable dosage forms aiming for targeted and effective drug delivery with minimal side effects. Method: Recently, application of nanotechnology through formulation of nanocarriers has acquired much more attention in treating different types of cancer tumors. Being explored in cancer therapy, nanocarriers have shown a promising capability to enhance intracellular uptake of active agents, promoting their accumulation in the tumor mass in addition to the reduction of the cellular toxicity compared to conventional chemotherapeutics. Results: In view of the above findings, this review discusses recent advances in nanotechnology-based carriers for cancer drug delivery, providing detailed description of different nanocarriers from historical perspective since the first developed carrier up to the new strategies adopted to formulate novel multifunctional targeted nanocarriers for cancer therapy. Conclusion: The findings of this review illustrate the potential of nanotechnology-based carriers as an emerging technology for more satisfying and selective cancer therapy.

Background: Nanoparticles (NPs) suffer from rapid clearance from body and require frequent dosing if long treatment is required. Method: In order to solve this problem for solid lipid nanoparticles (SLN) and prolong their action, SLNs were incorporated into thermo-responsive Poloxamer sol-gels and their fate was investigated in-vivo and in-vitro using a near infrared lipophilic fluorescent dye; dialkylcarbocyanin [1]. Leakage test, release of intact SLNs from sol-gel and SLN size and zeta potential were investigated. Biodistribution of DiR formulations (solution, free SLN and SLN-Gel) was investigated by whole-body and ex-vivo organ imaging after intraperitoneal injection in mice. SLN showed particle size of about 165 nm and a negative zeta potential of about -36 mV. Results: Leakage studies indicated that fluorescent probe does not release from SLNs. Imaging results revealed a steady profile for SLN-Gel over time, while the fluorescence intensity of solution and free SLN showed a burst followed by rapid clearance. Results also showed that SLN release occurs after gel erosion and follows a zero order profile. Conclusion: Our results indicate that NP-incorporated gel can be used to control the release of SLNs from application site and prolong their action in a sustained manner.

Background: Asenapine is an anti-psychotic agent approved by the US-FDA for treatment of acute schizophrenia and manic or bipolar I disorder in adults. It is poorly absorbed when administered orally, hence exhibits poor oral bioavailability, which limits its use in clinical practice. Objective: Enhancement in solubility of asenapine through complexation with three different cyclodextrins, viz. βCD, HPβCD and sulphobutylether-βCD (Captisol®) was attempted and compared due to its poor bioavailability. Method: Kneading method was used for preparation of inclusion complexes which were characterized by FTIR, DSC, and XRD methods. Extent of binding and stability of the 1:1 inclusion complexes were evaluated by molecular modelling and phase solubility studies. Pharmacokinetic studies were also carried out of these inclusion complexes. Results: Captisol® complex was the most stable amongst all complexes showing 4.9 times solubility enhancement of asenapine and 96% drug release at the end of 60 min, whereas asenapine maleate (uncomplexed drug) was released completely at the end of 120min. The Cmax and AUC values of Captisol® asenapine complex (AS-Captisol complex) were 2.8 and 2.3 times higher than the uncomplexed drug. Conclusion: This study thus demonstrated that Captisol® inclusion complex is an effective strategy for solubility and bioavailability enhancement of asenapine.

Background: Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. Method: To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment was synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method. According to the loading capacity, the best polymer was chosen. mPEG-PLA micelles were characterized in terms of drug entrapping efficiency, loading capacity, size, the crystalline state of AEP, stability and release profile. Meanwhile, the cytotoxicity of micelles on mouse breast cancer 4T-1 was investigated. Results: These micelle (mPEG-PLA-AEP) particles had a size of (92.84±5.63) nm and a high entrapping efficiency and loading capacity of (91.00±11.53)% and (32.14±3.02)%(w/w), respectively. The powder DSC showed that drugs were well encapsulated in the core of micelles. mPEG-PLA-AEP had a good stability against salt dissociation, protein adsorption and anion substitution and the solubility of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide(DDAG) in AEP increased 4.51 times and 2.12 times in water, and the solubility of DAG showed no difference. mPEG-PLA-AEP had the same release profile in different dissolution medium. Cytotoxicity testing in vitro demonstrated that mPEG-PLA-AEP exhibited higher cell viability inhibition in mouse breast cancer 4T-1 than free AEP. Conclusion: mPEG-PLA micelles offer a promising alternative for TCM therapy with higher solubility and improved antitumor effect.

Background: Microencapsulation is one of the most common techniques for the delivery of macromolecules; however, it can cause various stability problems, such as degradation or loss of bioactivity of the loaded molecules. For this reason, several techniques were investigated to load insulin into pre-formed porous microparticles (MPs). Objective: The high loading of insulin is a prerequisite of its delivery in sufficient concentration; hence we examined insulin loading in mesoporous silica (SBA15-NH2) as a model for uniformly porous microparticles using different loading methods and factors. Method: The MPs were characterized with respect to their morphology, porosity and pore diameter while insulin adsorption into the porous substrates was investigated using immersion and freeze-drying at different pH and initial peptide concentrations. MPs were further coated with Chitosan as a technique for pore blocking. Results: The results showed that the extent of insulin adsorption by freeze-drying varied depending on substrate affinity to insulin and pH where it could achieve the highest loading capacity at a pH near its isoelectric point. A significant increase in drug loading along with slower drug release was observed with Chitosan coated SBA15-NH2 MPs. In addition, the structural integrity of insulin was maintained after loading into the MPs, as confirmed by gel electrophoresis and fluorescent spectroscopy together with the in vivo study which in turn confirmed the preservation of insulin bioactivity in lowering blood glucose after oral administration. Conclusion: The present work displays the various factors that can control insulin loading in mesoporous silica MPs and their effects in enhancing the efficiency of insulin oral delivery using such substrates.

Background: Melatonin is an endogen substance with several physiological functions, acting as an important antioxidant. Our objective was to prepare nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) coated with polysorbate 80 (PLGA-PS80) or uncoated (PLGA) nanoparticles containing melatonin (MLT) and evaluate their in vitro cytotoxicity over erythrocytes and in vitro antioxidant activity. Methods: Nanoparticles were obtained by an emulsion-solvent evaporation method and characterized by size, morphology, polydispersity index, zeta potential, encapsulation efficiency, thermal properties and in vitro drug release profile. The in vitro cytotoxicity over erythrocytes was assessed by hemolysis assay and in vitro antioxidant was carried out by colorimetric assay using the radical 2,2-azinobis (3- ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS·+). Results: Mean size of the PLGA-PS80 and PLGA nanoparticles was 212 and 187 nm, and the encapsulation efficiency of MLT was 26 and 41%, respectively. Nanoparticles were spherical in shape and presented negative zeta potential. MLT was released from nanoparticles following the second order model and PLGA-PS80 presented more prolonged MLT release. Conclusion: Cytotoxicity over erythrocytes was assessed and both nanoparticles containing MLT demonstrated lack of hemolysis. Scavenging activity over ABTS·+ demonstrated both nanoparticles containing MLT were more efficient than free drug, and MLT-loaded PLGA nanoparticles presented the higher in vitro antioxidant activity. The study concluded that PLGA and PLGA-PS80 nanoparticles are promising carriers for MLT.

Background: Docetaxel (DTX) has been used to treat several types of cancers, but it has provided pharmaceutical challenges due to its poor water solubility and toxicities associated with the co-solvents (tween-80 and ethanol). Nanopolymer therapeutics can be engineered to deliver anticancer agent specifically to cancer cells, thereby leaving normal healthy cells unaffected by toxic drugs such as DTX. The objective of the present study was to synthesize the polyacrylic acid (PAA)-DTX conjugate (PAADC) and preparation of nanopolymer therapeutics such as PAADC/DSPE-mPEG2000 mixed micelles (PAADC-DP MMs). Methods: The prepared PAADC-DP MMs were characterized for mean particle size and zeta potential, in vitro release profile using dialysis technique, hemolytic behavior against human blood, and cytotoxicity against human cancer cell line (A549) using MTT assay. In vivo acute toxicity of PAADC-DP MMs was determined in albino mice at intravenous single dose of 40 mg/kg. Results: PAADC-DP MMs showed mean particle size of 443±9nm. PAADC-DP MMs showed maximum DTX loading (DTX equivalent; 90.5±2.7%) with minimum DSPE-mPEG2000 molecules (1:1 ratio), while to load 77.9±2.2% of plain DTX, more DSPE-mPEG2000 is required(1:10 ratio). The developed PAADC-DP MMs system showed significantly lower CMC (5 ng/mL), sustained release profile (28.6±1.9% after 48 h of study), lower hemolytic behavior (13.7±1.3% of hemolysis ratio at 40 μg/mL concentration and after 1 h incubation), higher in vitro cytotoxicity (IC50 of 0.0064±0.001 nM after 48 h study) and remarkably reduced in vivo toxicity (9.9±2.1% body weight loss) in mice when compared to marketed Taxotere®. Conclusion: The obtained results clearly demonstrated that the developed PAADC-DP MMs system is a promising approach for cancer chemotherapy with reduced toxicity.

Background: The aim of this research was to engineer solid dispersion lipid particles (SDSLs) in which a solid dispersion (SD) was encapsulated to form the core of solid lipid particles (SLs), thereby achieving an efficient enhancement in the dissolution of a poorly water-soluble drug. Methods: Ultrasonication was introduced into the process to obtain micro/nanoscale SLs. The mechanism of dissolution enhancement was investigated by analysing the crystalline structure, molecular interactions, and particle size of the formulations. Results: The drug release from the SD-SLs was significantly greater than that from the SD or SLs alone. This enhancement in drug release was dependent on the preparation method and the drug-topolymer ratio of the SD. With an appropriate amount of polymer in the SD, the solidification method had the potential to alter the drug crystallinity to an amorphous state, resulting in particle uniformity and molecular interactions in the SD-SLs. Conclusions: The proposed system provides a new strategy for enhancing the dissolution rate of poorly water-soluble drugs and further improving their bioavailability.

Background: Liposomes have been widely used in gene transfection and drug delivery systems due to their excellent biocompatibility and encapsulation ability, especially, the ability to deliver the gene/drug into the cells via the membrane fusion. Thermosensitive liposomes have been proven to be a precise and effective method for cancer treatment in many preclinical studies. But the imperfect crystalline arrangement between grains occurred, resulting in planar defects at the boundaries of membranes, compromising the stability of thermosensitive liposomes. Objective: In the present study, we developed a facile method to improve the stability of ordinary thermosensitive liposomes by introducing organic-inorganic hybrid materials with local Si-O-Si net. Method: A cerasome forming lipid, N, N-Dihxadecyl-N'- [(3-triethoxysilyl) propyl] urea, was synthesized and then introduced into the thermosensitive lipids to form the composite liposomes (named as cera-liposomes). The effects of the cerasome forming lipid on the cera-liposomes characteristics, including the morphology, drug loading, Zeta potential and stability of vesicles, were investigated. Results: Cera-liposomes were thermosensitive, and they had a loading efficiency over 2 folds more than conventional thermosensitive liposomes. With the enhanced sustain of Si-O-Si, cera-liposomes were able to avoid collapsing and fusing during storage, and had a good resistance to nonionic surfactant. More than 80% drug was still retained after storage of 15 days at room temperature. Conclusion: The cerasome forming lipid showed potential in improving the stability of thermosensitive liposomes. This novel kind of cera-liposomes could be a stable and effective drug carrier for anticancer applications.

Background: Retinal neovascularization (NV) is the leading cause of blindness in the majority of ocular diseases. Several treatment approaches have been developed for retinal NV; of these methods, instillation of nanoparticles into the conjunctival sac has shown potential for retinal NV treatment because it does not cause physical damage and is easy to operate. Methods: In this study, honokiol-loaded chitosan/sulfobutylether-β-cyclodextrin nanoparticles (HKCS- NPs) were prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol and sulfobutylether-β-cyclodextrin was used to incorporated insoluble honokiol into chitosan nanoparticles, which were prepared through ionotropic gelation. Results: HK-CS-NPs featured a spherical surface with a narrow size distribution of polydispersity index less than 0.250, a mean size range of 373–523 nm, a positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of 84.92%. In vitro release studies showed an initial burst release phase and a sustained release phase of nanoparticles. Moreover, in vivo study showed that HK-CS-NPs exhibited good ocular tolerability and could improve ophthalmic bioavailability of honokiol. In particular, the maximum concentration of honokiol after administration of HK-CS-NPs was enhanced by 1.65 times compared with that after instillation of the honokiol suspension alone. Conclusion: This study proposes HK-CS-NPs as a potential ophthalmic delivery system.