Current Drug Delivery - Volume 17, Issue 8, 2020

Background: Solubility is one of the significant pre-formulation properties which regulate the desired concentration of drug in the systemic circulation. Most of the newly discovered chemical entities show poor solubility which consequently leads to poor bioavailability. To enhance the bioavailability of such type of drugs is a big challenge for pharmaceutical scientists. Liquisolid technology is a new and advanced technology used to transform the liquid medication into dry, free-flowing and easily compressible dosage form incorporation with the carrier and coating material. Objectives: This review represents the technical perspective of Liquisolid technologies that overcome the demerits of classic formulation strategies and amend the bioavailability of the poorly soluble drug. This technique is also approaches the stability, hygroscopicity and agglomeration issue which are mainly occurring in other techniques for solubility enhancement. Conclusion: Several technologies have been utilized to minimize the solubility problem but due to the complicated and expensive machinery fails to achieve the desired bioavailability of the poorly soluble drugs. Therefore, Liquisolid technology has been introduced as an innovative and promising technique that recovers the demerits of classic formulation strategies and also improves the bioavailability of the poorly soluble drug. This article exhibits the technical approach of the liquisolid system by improving the solubility as well as bioavailability of water-insoluble drugs.

Natural polysaccharides, as well as biopolymers, are now days widely developed for targeting colon cancer using various drug delivery systems. Currently, healing conformations are being explored that can efficiently play a multipurpose role. Owing to the capability of extravagance colonic diseases with the least adverse effects, biopolymers for site specific colon delivery have developed an increased curiosity over the past decades. Inulin (INU) was explored for its probable application as an entrapment material concerning its degradation by enzymes in the colonic microflora and its drug release behavior in a sustained and controlled manner. INU is a polysaccharide and it consists of 2 to 1 linkage having an extensive array of beneficial uses such as a carrier for delivery of therapeutic agents as an indicative/investigative utensil or as a dietary fiber with added well-being aids. In the main, limited research, as well as information, is available on the delivery of therapeutic agents using inulin specifically for colon cancer because of its capability to subsist in the stomach’s acidic medium. This exceptional steadiness and robustness properties are exploited in numerous patterns to target drugs securely for the management of colonic cancer, where they effectively act and kills colonic tumor cells easily. In this review article, recent efforts and inulin-based nano-technological approaches for colon cancer targeting are presented and discussed.

Background: At present, the controlled local drug delivery is a very promising approach compared to systemic administration, since it mostly targets the affected tissue. In fact, various drug carriers for local delivery have been prepared with improved therapeutic efficacy. Objective: in situ polymer gels are drug delivery systems that not only present liquid characteristics before their administration in body, but once they are administered, form gels due to gelation. Their gelation mechanism is due to factors such as pH alteration, temperature change, ion activation or ultraviolet irradiation. in situ gels offer various advantages compared to conventional formulations due to their ability to release drugs in a sustainable and controllable manner. Most importantly, in situ gels can be used in local drug delivery applications for various diseases. Methods: This review includes the basic knowledge and theory of in situ gels as well as their various applications according to their administration route. Results: Various natural, semisynthetic, and synthetic polymers can produce in situ polymeric gels. For example, natural polysaccharides such as alginic acid, chitosan, gellan gum, carrageenan etc. have been utilized as in situ gels for topical delivery. Besides the polysaccharides, poloxamers, poly(Nisopropylacrylamide), poly(ethyleneoxide)/ (lactic-co-glycolic acid), and thermosensitive liposome systems can be applied as in situ gels. In most cases, in situ polymeric gels could be applied via various administration routes such as oral, vaginal, ocular, intranasal and injectable. Conclusion: To conclude, it can be revealed that in situ gels could be a promising alternative carrier for both chronic and immediate diseases.

Background: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Current treatments are restricted to a small number of drugs that display both severe side effects and a potential for parasites to develop resistance. A new N-(3,4-methylenedioxyphenyl)-N'- (2-phenethyl) thiourea compound (thiourea 1) has shown promising in vitro activity against Leishmania amazonensis with an IC50 of 54.14 μM for promastigotes and an IC50 of 70 μM for amastigotes. Objective: To develop a formulation of thiourea 1 as an oral treatment for leishmaniasis, it was incorporated into Nanoparticles (NPs), a proven approach to provide long-acting drug delivery systems. Methods: Poly (D,L-Lactic-co-Glycolic Acid) (PLGA) polymeric NPs containing thiourea 1 were obtained through a nanoprecipitation methodology associated with solvent evaporation. The NPs containing thiourea 1 were characterized for Encapsulation Efficiency (EE%), reaction yield (% w/w), surface charge, particle size and morphology by Transmission Electron Microscopy (TEM). Results: NPs with thiourea 1 showed an improved in vitro leishmanicidal activity with a reduction in its cytotoxicity against macrophages (CC50>100 μg/mL) while preserving its IC50 against intracellular amastigotes (1.46 ± 0.09 μg/mL). This represents a parasite Selectivity Index (SI) of 68.49, which is a marked advancement from the reference drug pentamidine (SI = 30.14). Conclusion: The results suggest that the incorporation into NPs potentiated the therapeutic effect of thiourea 1, most likely by improving the selective delivery of the drug to the phagocytic cells that are targeted for infection by L. amazonensis. This work reinforces the importance of nanotechnology in the acquisition of new therapeutic alternatives for oral treatments.

Background: Oseltamivir Phosphate (OP) is an ethyl ester prodrug prescribed for the treatment of influenza virus infection. Current marketed formulations of OP have been observed to be supplemented with an adverse effect during post-marketing surveillance. These prerequisites are sufficed by developing a sustained release Dry Powder for Inhalation (DPI). Objective: The objective of the present study was to develop OP-DPI by an innovative formulation approach comprising of Immediate (IR) and Sustained (SR) Release portions. Methods: DPI formulation comprising IR and SR portions were prepared by spray drying technique using Hydroxy Propyl Methyl Cellulose (HPMC) as the rate-controlling polymer for SR portion. The spray-dried product was further characterized for various pharmaco-technical, in-vitro and in-vivo parameters. Results: OP-DPI showed a burst release of 49% within 15 min further sustaining the drug release up to 9 hrs. The in-vitro aerodynamic performance of OP-DPI showed maximum deposition at stage 3 and Fine Particle Dose (FPD) of 1.08 mg indicating deposition in the upper respiratory tract. Solid-state characterization by DSC and XRD indicated the partial amorphization of OP due to spray drying. In-vivo toxicological examination revealed no sign of inflammation, indicating the safety of the developed formulation. Accelerated stability study as per ICH guidelines displayed no significant change in the solid-state characterization and drug-related performance of OP-DPI. Conclusion: Prepared novel and scalable OP-DPI may have the potential to overcome the problems associated with existing marketed dosage forms of OP. Further, localized drug delivery of the antiviral drug through the pulmonary route might be clinically beneficial in controlling the viral proliferation.

Background: Ginkgolides are widely used in cardio-protective therapy; however, poor bioavailability currently limits their application. Objective: The purpose of this study was to demonstrate whether solid dispersions prepared with Low- Molecular-Weight Chitosan (LMWC) could improve the protective effect of ginkgolides on Myocardial Injury (MI). Methods: Ginkgolide Solid Dispersions (GKSD) were prepared with LMWC. Their properties were then characterized using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. In vivo pharmacokinetic studies were performed in rats, and the protective effect of GKSD on MI was investigated by western blotting and immunohistochemical analyses. Results: Drug dissolution testing showed that GDSD were released at a significantly higher rate than ginkgolides, dissolved by alternative methods, suggesting that LMWC facilitates the release of ginkgolides. Differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy all showed that GKSD was amorphous. In-vivo testing revealed larger AUC0-t, higher Cmax, and shorter Tmax for GKSD compared to that in original ginkgolides. Myocardial injury was induced in rats with isoproterenol to test the protective effect of GKSD. GKSD alleviated MI and reduced myocardial fibrosis, as observed by Hematoxylin and Eosin staining. Compared with the crude drug group, the secretion of malonyl dialdehyde and nitric oxide and expression of NOX-2 and NOX-4 were lower. The activities of the cardiac marker enzymes SOD, CAT, GPX, GPX-1, and GSH were higher in GKSD-administered rats, indicating a beneficial effect of GKSD in eliminating free radicals during myocardial injury. Additionally, western blotting and immunohistochemical analysis showed that GKSD markedly reduced the expression of signaling proteins RHOA, ROCK1, ROCK2, and RAC1. Conclusion: Solid dispersions prepared with low molecular weight chitosan improved the oral bioavailability of ginkgolide and enhanced its protective effect on myocardial injury.

Objective: To prepare the sustained-release complex, quercetin was incorporated with β- cyclodextrin (β-CD) and the effect of β-CD–quercetin complex on the growth of ethanol-injuried hepatocytes was studied. Methods: By using scanning electron microscopy, infrared spectroscopy, and release rate analysis, β- CD–quercetin complex was identified. The effect of different concentrations of β-CD–quercetin complex on the growth of ethanol-damaged hepatocytes at different time was observed by using MTT assay, and the cell quantity and morphology were observed by using hematoxylin–eosin staining. By using single-cell gel electrophoresis, the prevention of β-CD–quercetin complex from the DNA damage of ethanol-damaged BRL-3A cells was studied, and Olive tail moment was calculated. Results: β-CD–quercetin complex as the sustained-release complex was successfully prepared. The ethanol induced damage of BRL-3A cells could be prevented by 20, 40 and 80 mg/L of quercetin complex, and the protection mechanism of hepatocyte was related to the antioxidation of DNA. Conclusion: Quercetin sustained-release complex could be prepared with β-CD, and it might be used to treat alcoholic liver disease.