Current Drug Delivery - Volume 15, Issue 10, 2018

Recently, electrospun polymeric nanofibers have proven to be an interesting strategy for drug delivery systems application. The high surface-to-volume ratio of the fibers can improve some processes, such as cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into polymeric nanofibers, to be used as drug delivery systems. For instance, it presents the reports on drugs with different bioactivities such as antiinflammatory, anti-microbial, anticancer, cardiovascular, anti-histamine, gastrointestinal, palliative and contraceptive drugs, etc. It also analyzes the electrospinning techniques used in each system, as well as the polymers used as matrices for the preparation of the nanofibers; unfolding the advantages of electrospun polymeric nanofibers over other drug delivery systems. This review intends to enlist and summarize the reported literature concerning this topic. In addition, it proposes future research in the field.

Botulinum neurotoxin type A (BoNT/A) is a toxin that inhibits the release of stimulatory neurotransmitter (acetylcholine) at the neuromuscular synapses. In recent years, many patients with muscle contraction disorders have greatly benefited from the therapeutic ability of this biological drug. On the other hand, the injection of this bio drug is accompanied by some side effects such as irritation, bruising, inflammation, pain, bleeding at the site of injection. Recently, a tendency has been observed among scientists to create new techniques to offer conventional injectable drugs the ability of transdermal delivery. Such promising drugs can be applied in various forms from gel, cream, and ointments to ready-to-use pads. This would eliminate a need for high drug doses to release the drug gradually at the site of application while at the same time, lower the side effects. Here, we discuss the possibility of noninvasive administration of BoNT/A in order to reduce the side effects of drug injection.

Surgical operations are impossible without administering proper analgesia. Advancement in the field of anesthesia has invariably resulted in the accomplishment of all surgical processes without any inconvenience. Admittedly, the use of noble gas is on the decline. The noble gases may not interact chemically with any other substance under normal temperature and pressure but they may interact with proteins and lipids. Different anesthetic molecules may stimulate either proteins or lipids in membrane. There is a connection between the anesthetic molecules and the hydrophobic region of the membrane. In the present review, we attempt to highlight the interaction between the anesthetic molecule with proteins and lipids and their effects. We sketched few noble gases and some other existing molecules such as halothane and alcohol which interacted with proteins and lipids.

Chirality is now a key area in the field of research. Researchers are well versed with analytical separations but at the same time, they are unaware of the growth in the field of chiral separation. According to the United States Food and Drug Administration (US FDA) guidelines, it is mandatory to separate chiral drugs before they are marketed. Chiral separation has gained importance in the last 10 years due to the differential biological responses of the enantiomers in chiral environment. Identical physical and chemical properties of the enantiomers pose a major challenge for the separation of chiral compounds. Further, bioanalytical method development is also necessary to throw light on the fate of separated enantiomers in biological environment. High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE) are the most widely used techniques for such separation. Antihistamines are a class of drugs that are represented by a wide number of chiral compounds. Hence this review focuses on enantioseparation of chiral antihistamine drugs. It begins with a brief discussion about antihistamine drugs, chiral separation and its need for study, followed by a brief overview of the analytical and bio-analytical work carried out on different chiral antihistamine drugs. The analytical and bio-analytical techniques that are used include HPLC, CE and some new techniques.

Background: Effective postoperative pain control is essential for the recovery of surgical patients. However, long-term analgesia can seldom be achieved with the existing medications. The injectable implants prepared by biodegradable polyesters can be conveniently used during the surgery and slowly release analgesics near the operative incision for a long period. Method: In this study, we prepared lidocaine hydrochloride (Lido-HCl)-loaded injectable poly(lacticco- glycolic acid) (PLGA) implants for prolonged analgesia. The optimized formulation of this injectable implant sustained drug release for up to 5 days, with a cumulative release of 85.8%±1.9% in the in vitro release experiment. Results: The in vivo release of the implants in rats showed good consistency with the in vitro release. The pharmacokinetics of Lido-HCl implants in the thigh muscle of rats was evaluated, and the AUC0-120 h of the Lido-HCl implant was 11.4 times that of Lido-HCl solution, indicating a good sustained release function of the implant. The pharmacodynamics of Lido-HCl implants was measured by the hot plate test. The Lido-HCl solution blocked the sciatic nerve of rats for less than 4 h, while the Lido-HCl implant efficiently blocked the nerve for approximately 120 h. Conclusion: These results demonstrated that the PLGA-based injectable implant is a suitable carrier for postoperative pain control.

Background: Drug design and discovery studies still remain of great importance in the search for more convenient chemotherapeutic to avoid the drug resistance, systemic toxicity or the longterm side effects. Objective: A series of mononuclear gold (III) and platinum (II) complexes based on 4-dihydroxyboryl- DL-phenylalanine (BPA) was designed and synthesized, for the first time, by using 2, 2'-dipyridyl (L1) and 4, 4'-diaminobibenzyl (L2) ligands. Characterization of the synthesized complexes was achieved by using 1H-NMR, IR, MS and elemental analyses. Method: MTT cell viability, endothelial tube formation, cancer cell colony formation and TRITCphalloidin cytoskeleton staining assays were performed on human umbilical vein endothelial (HUVEC) and human lung adenocarcinoma (A549) cells to establish the anticancer and anti-angiogenic activities of the complexes. It was determined that the organometallic complexes that include 2, 2'-dipyridyl ligand have higher antiproliferative activity than L2-based complexes in the micromolar range. Colony formation experiments showed that the anchorage-independent growth ability of A549s was significantly affected by the complexes in a concentration-dependent manner though L1-based complexes were more effective than L2-based ones. Results: It was also clearly observed that the complexes have significant anti-angiogenic and cytoskeleton alterative activities. Consequently, the phenylalanine-based organometallic complexes seem to have anti-lung cancer and anti-angiogenic activities depending on the ligand type and a great potential in oncology drug development because phenylalanine amino acid has an ability to cross the cell membrane by using L-amino acid transport system. Conclusion: Design, synthesis and activity studies with amino acid analogs should be therefore increased to discover more efficient drugs to cure cancer diseases.

Background: Hesperetin (HSP) is a low water-soluble flavanone aglycone with low bioavailability. Objectives: This study aimed at enhancing the hepatoprotective effects of HSP by a combinatory technique based on solid dispersions of co-crystals of HSP. Methods: Co-crystals were prepared using citric acid, tartaric acid, caffeine and isonicotinamide (INM) using two methods of solvent evaporation and co-grinding. The solid dispersion of co-crystals with different ratio of INM, PVP K30 and drug was prepared by the solvent evaporation method. The resulting material was characterized by DSC, XRD, FTIR and SEM, their saturated solubility and dissolution rate were compared to the pure drug. Finally, liver toxicity was induced in rats by carbon tetrachloride (CCl4) and mice were treated with different formulations of HSP. The liver function was tested by measurement of glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP) and bilirubin as well as histopathological tests. Results: Although saturation solubility of HSP was enhanced about 5 times by co-crystals of HSP/INM (1:2), solid dispersions of the co-crystals of HSP obtained from PVP K30 and INM enhanced it up to 200 folds. Functional parameters of liver in rats pretreated with a solid dispersion of co-crystals of HSP were significantly lower than those with pure HSP and co-crystals of INM/HSP with 2:1 ratio. Furthermore, this formulations reduced liver damage effectively compared with the CCL4 group. Conclusion: Solid dispersion of HSP co-crystals synergistically attenuates hepatic toxicity of carbon tetrachloride oxidative stress in rats more effectively than its solid dispersions or co-crystals alone.

Background: There has been a growing concern in transdermal drug technology over the past several decades. As a novel transdermal delivery system, Lyotropic liquid crystals (LLC) still face challenges such as drug loading, limited drug permeation and instability of systems. LLC system is so sensitive that a very subtle change in composition may induce a phase transformation or conversion of spatial configuration, and result in a diverse percutaneous delivery subsequently. Objective: To find out the effects of hydrophilic and lipophilic components on the structure and transdermal properties of LLCs, hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a model drug and a skin permeation enhancer, respectively, several formulations were prepared and compared. Method: The structure of LLC was evaluated by visual observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin penetration of SH across the rat skins. Fourier transform infrared spectroscopy (FTIR) was recorded to evaluate the intermolecular interaction between the LC samples and stratum corneum (SC). Conclusion: The results showed that a controlled transdermal process might be obtained by adjusting the ratios of different drugs or loading doses when LLCs with dual-components were applied.

Background: It is well documented in the scientific literature that high blood pressure can lead to cardiovascular disease. Untreated hypertension has clinical consequences such as coronary artery disease, stroke or kidney failure. Diltiazem hydrochloride (DH), a calcium-channel blocker, and perindopril erbumine (PE), an inhibitor of the angiotensin converting enzyme are used for the management of hypertension. Objective: This project will examine the effect of microneedle rollers on the transport of DH and PE across pig ear skin. The use of the transcutaneous route of administration reduces and in sometimes eliminates the trauma and pain associated with injections. Furthermore, there is increased patient compliance. The purpose of this project was to study the effect of stainless steel microneedles on the transdermal delivery of DH and PE. Method: We utilized vertical Franz diffusion cells to study in vitro transport of DH and PE across microneedle- treated pig ear skin. Confocal laser scanning microscopy (CLSM) was used to characterize microchannel depth. Transdermal flux values were determined from the slope of the linear portion of the cumulative amount versus time curve. Results: There was a 113.59-fold increase in the transdermal permeation of DH following the application of microneedle roller compared to passive diffusion. Conclusion: In the case of PE, there was an 11.99-fold increase in the drug transport across pig skin following the application of microneedle rollers in comparison with passive diffusion. Student's t-test and Mann-Whitney's rank sum test were used to determine statistically significant differences between experimental and control groups.