Phytochemical Screening and Antimicrobial Activity Evaluation of Selected Medicinal Plants in Ethiopia.

Background: The emergence and spread of resistant microbes continue to be a major public health concern. Effective treatment alternatives, particularly from traditionally used medicinal plants, are needed. Objective: The main objective of this study was to conduct phytochemical screening and antimicrobial activity evaluation of selected traditionally used medicinal plants in Ethiopia. Methods: The ethnomedicinal use value frequency index (FI) was used to select twelve medicinal plants. Phytochemical classes of compounds were screened using different standard methods. Anti-microbial activities of plant extracts were evaluated against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimum inhibitory concentrations were measured using the broth micro-dilution method. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0 and the findings were presented descriptively and using non parametric one-way ANOVA analysis (Kruskal-Wallis/Ddunn's test). Results: The phytochemical constituents identified were flavonoids, alkaloids, glycosides, phenols, saponins, steroids, and terpenoids, with flavonoids, alkaloids, and phenols being the most abundant. The crude extracts and chloroform fractions of the extracts showed an activity against the tested strains. The crude extract of Thalictrum rhynchocarpum Quart.-Dill. and A.Rich root demonstrated superior activity against all the tested strains with the lowest minimum inhibitory concentrations of 0.48 µg/mL against Staphylococcus aureus and Escherichia coli; 0.98 µg/mL against Klebsiella pneumoniae, Pseudomonas aeruginosa; and 3.90 µg/mL against Candida albicans, which are even better than the reference drug, gentamicin and clotrimazole. Conclusion: The majority of evaluated medicinal plants demonstrated remarkable activity against tested microbial strains, which can be attributed to the presence of secondary metabolites of different classes of compounds. The finding provided scientific evidence for the use of these traditionally used medicinal plants.

Characterization of Boswellia rivae Engl Resin as a Potential Use for Pharmaceutical Excipient.

Pharmaceutical excipients derived from natural sources like resins are nowadays meritoriously used in the formulation of drugs. Resins of natural origin have many advantages over chemically synthesized substances; they are safer, nontoxic, less expensive, biodegradable, and widely available. To our knowledge, resins from plants have been not sufficiently explored for application in pharmaceutical formulations. Thus, in the present study, a resin isolated from Boswellia rivae Engl was characterized for its potential use as a pharmaceutical excipient. Method. The resin was extracted from the oleo gum resin of Boswellia rivae Engl, which involved the removal of volatile oils, gum, and Boswellic acid contents. The dried resin powder was then characterized for its micromeritic properties, heavy metal contents, moisture content, moisture absorption power, pH, solubility, swelling property, and acute toxicity profile. Moreover, the crystal nature and the chemical functionality of the resin were evaluated by using X-ray diffraction and Fourier transform infrared spectrometry, respectively. Results. The yield of the neutral resin was 13.17%, and the powder was pale yellow and had irregular surfaces. The resin was freely soluble in organic solvents but almost insoluble in water. The moisture content of the dried extract was 2.5% while its moisture absorption capacity was 2.5%, 4%, and 5.47% at 40%, 60%, and 75% RH, respectively. Besides, the maximum swelling capacities of the resin observed were 40%, 37%, and 30% at 350C, 300C, and 250C, respectively. The bulk powder exhibited a 1.21 Hausner ratio, 36.497 angles of repose, and 17.03% Carr's index, indicating the fair flowability of the powder. Heavy metals such as zinc, chromium, and cobalt were detected at a low level while elements like copper, manganese, lead, and cadmium were absent. The X-ray diffraction study revealed that the crystallinity index of the powder was 42.7% with a crystal size of 994.5A. The Boswellia resin could be safe in mice up to 3 g/kg of their body weight. In conclusion, the physicochemical properties of the resin powder investigated reveal its potential application as pharmaceutical additives in the formulation of modified release solid dosages forms like tablets and microcapsules.

Quality-by-Design Principles Applied to the Establishment of a Pharmaceutical Quality Control Laboratory in a Resource-Limited Setting: The Lab Water.

Quality-by-design (QbD) is defined as a systematic approach to design and develop a product/service based on sound science and quality risk management. It is already frequently applied in the pharmaceutical industry mainly in the development of pharmaceutical products and analytical methods but is not well established in the setup of facilities like quality control (QC) laboratory (lab). Therefore, lab QbD (lQbD) concept is introduced considering lab water purification system as an example. The water purification system comprising distillation unit coupled with Nanopure Analytical Ultrapure Water System combined with a 0.2-micron filter was established in Jimma University Laboratory of Drug Quality (JuLaDQ). The consistent capability of the established water purification system was evaluated through routine monitoring of the critical quality parameters (i.e., physicochemical, HPLC-DAD chromatogram total peak area, and resistivity) of freshly prepared lab water for a period of one year. In addition, quality of different grade water (tap water, distilled water (before and/or after cleaning distillation unit), and fresh ultrapure water (18.2 MΩ × cm at 25°C)) used in JuLaDQ was evaluated. The results of routine analysis of water quality revealed that HPLC global peak area at 210 and 254 nm could serve as one of the discriminatory control strategies to evaluate the capability of water purification system to produce the desired quality of lab water; and thus, we proposed a specification limit of 5,000 mAU∗s and 5,500 mAU∗s for global peak area at 254 and 210 nm, respectively, as system suitability parameter.

Investigating the knowledge, perception, and practice of healthcare practitioners toward rational use of compounded medications and its contribution to antimicrobial resistance: a cross-sectional study.

BACKGROUND: Pharmaceutical compounding ensures access of individuals with specific requirements to individualized therapy. However, there is an inconsistency of compounded medication quality. Therefore, advancing the rational use of compounded medication is essential for patient safety and medication effectiveness. OBJECTIVE: The presented study was aimed to investigate the healthcare practitioners' knowledge, perception, and practice of extemporaneous compounding and its contribution to the prevalence of antimicrobial resistance. METHOD: A descriptive cross-sectional survey using a structured questionnaire was conducted. The study participants were 300 healthcare practitioners working in Jimma University Medical Center, hospital pharmacies, and community pharmacies in Jimma and Mettu Town, Southwest Ethiopia. RESULTS: Most respondents were pharmacists (62.7%) and first-degree holders (48.3%). The majority of them had experience in administering (57.7%), preparing (38%), prescribing (21%), and repackaging and labeling (14%) compounded medications. Commonly they request compounded medications when prepackaged products (77.7%) and needed dosage regimens (72.3%) were not available in the market. However, most of them believed that compounded medications might lack quality (49%) and had poor patient compliance (40.7%). Moreover, they fear that inappropriate preparation processes (75%) and under-dose administration (59%) of compounded medication might contribute to the development and prevalence of antimicrobial resistance. CONCLUSION: Most healthcare practitioners practice rational use of compounded medications and strongly agree that inappropriate compounding of antimicrobials contributes to antimicrobial resistance development.

In vitro skin retention and drug permeation study of Tongluo-Qutong rubber plaster by UPLC/UV/MS/MS

Abstract Tongluo-Qutong rubber plaster (TQRP), a typical Chinese patent medicine that contains 13 different herbal remedies, is widely used in clinical practice for the treatment of cervical spondylosis and osteoarthritis. However, due to a lack of in vitro transdermal studies, the active ingredients of TQRP have not been fully elucidated. This presents a huge obstacle for quality evaluation, pharmacokinetic studies and clinical safety assessment of TQRP. In this work, a UPLC/UV/MS/MS method was established and validated to evaluate five analytes in TQRP. The validation demonstrated linearity (r > 0.99), specificity (no co-eluting peaks at the retention times of the analytes), and precision (RSD < 15%) within acceptable parameters. A skin permeation study was performed to determine the concentrations of drugs delivered to the dermis. The 24-hour cumulative permeation of ferulic acid, aleo-emodin, emodin and piperine were 303.68, 709.31, 671.06 and 25561.01 ng/cm2, respectively. According to the fitting data of the TQRP active components, skin permeation was mainly due to a combination of passive diffusion and drug release after matrix erosion

Chemical Composition, Protective Effects, and Mechanisms of Volatile Oil from Fructus Gleditsiae Abnormalis with Nasal Administration against Ischemic Injury in HFD and MCAO-Induced Rats.

Fructus Gleditsiae Abnormalis (FGA) has been used as a traditional Chinese medicine (TCM) for the treatment of stroke caused by phlegm and blood stasis. However, its substance basis and mechanism of action are currently unknown. This study is aimed to analyze the constituents of the volatile oil in FGA (VOFGA) using gas chromatography coupled with mass spectrometry (GC-MS) and explore the underlying effects and mechanisms of VOFGA in the prevention and treatment of ischemia stroke. An in vivo ischemia model was constructed by combination treatment of high-fat diet (HFD) and middle cerebral artery occlusion (MCAO) method. After administration, the cerebral infarction volume, the brain water content, hemorheology, blood lipids, inflammatory factors, oxidative stress indicators, Bax, Bcl-2, and cleaved caspase-3 and histological examination (HE) were determined and observed to explore the underlying effects and mechanisms of VOFGA against ischemia stroke. The results showed that forty components were determined after analyzed by GC-MS, and the percentage content of palmitate, paeonol, violetone, linalool, salpinol, citral, and methyleugenol were 4.69%, 5.2%, 3.56%, 3.31%, 2.42%, 2.65%, and 1.67%, respectively. The high dose of VOFGA could inhibit neurological damage; reduce the cerebral infarction volume and brain water content; improve whole blood viscosity and red blood cell aggregation index at various shear rates; reduce the levels of TG, TC, LDL-C, TNF-α, IL-1ß, MDA, and NO; increase the contents of HDL-C, IL-10, and SOD; downregulate the expressions of Bax and cleaved caspase-3 in the ischemic regions; and upregulate the expressions of Bcl-2. These effects implied that VOFGA may exert neuroprotective effects via inhibiting ischemia-triggered oxidative damage-regulating blood lipid factors and reducing the production of proinflammatory mediators against cerebral I/R injury and neuronal apoptosis. The VOFGA presents a potential treatment value for cerebral ischemic stroke, and it may offer insights into discovering new active compounds for the treatment of ischemic stroke.

Combination of cell-penetrating peptides with nanomaterials for the potential therapeutics of central nervous system disorders: a review.

Although nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood-brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood-brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

Inventory management performance for laboratory commodities in public hospitals of Jimma zone, Southwest Ethiopia.

BACKGROUND: Maintaining an efficient and effective inventory management system ensures a reliable supply of laboratory commodities. The aim of this study was, therefore, to assess the performance of inventory management for laboratory commodities in public hospitals in the Jimma zone. METHODS: A facility-based cross-sectional descriptive study, accompanied by a qualitative method, was conducted in seven public hospitals between April 30 and May 29, 2019. We collected data through document reviews (225 bin-cards), physical observation, self-administered questionnaires, and in-depth interviews. The quantitative data were analyzed using Excel spreadsheets and SPSS version 24. Fifteen key informants of different backgrounds took part in the qualitative study. The data were then analyzed using thematic analysis techniques. RESULTS: All the public hospitals in the zone were included in the study, making a response rate of 100%. Of the total estimated bin-cards, 225 (69.9%) of them held along with the items, and only 30.4% of them filled accurately. In four of the hospitals, pharmacists determined how much to order. Five of the hospitals used average monthly consumption data to calculate purchase quantity. Over the past 6 months, four of the hospitals had placed at least one or two emergency orders. The wastage rate of the commodities in the hospitals was 27.2% and resulted in a loss of about 10,248.5 US dollars. The hospitals had met 70.6% of the criteria for proper storage conditions. Budget constraints, absence of prompt administrative support, lack of staff commitment, and frequent shortages of commodities on the part of suppliers were major bottlenecks of inventory management. CONCLUSIONS: The hospitals had weak inventory management practices, showed by inaccurate records, stock-outs (frequent emergency orders), a high wastage rate compared to national baseline statistics, and the storage conditions below the standard.

Nano-Strategies for Improving the Bioavailability of Inhaled Pharmaceutical Formulations.

Pulmonary pharmaceutical formulations are targeted for the treatment of respiratory diseases. However, their application is limited due to the physiological characteristics of the lungs, such as branching structure, mucociliary and macrophages, as well as certain properties of the drugs like particle size and solubility. Nano-formulations can ameliorate particle sizes and improve drug solubility to enhance bioavailability in the lungs. The nano-formulations for lungs reviewed in this article can be classified into nanocarriers, no-carrier-added nanosuspensions and polymer-drug conjugates. Compared with conventional inhalation preparations, these novel pulmonary pharmaceutical formulations have their own advantages, such as increasing drug solubility for better absorption and less inflammatory reaction caused by the aggregation of insoluble drugs; prolonging pulmonary retention time and reducing drug clearance; improving the patient compliance by avoiding multiple repeated administrations. This review will provide the reader with some background information for pulmonary drug delivery and give an overview of the existing literature about nano-formulations for pulmonary application to explore nano-strategies for improving the bioavailability of pulmonary pharmaceutical formulations.

Physicochemical and Pharmacokinetic Evaluation of Spray-Dried Coformulation of Salvia miltiorrhiza Polyphenolic Acid and L-Leucine with Improved Bioavailability.

Background:Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiovascular diseases and currently it is administered orally or intravenously. However, SMPA is poorly absorbed orally and quickly eliminated in vivo. A long-term frequent intravenous administration leads to poor patient compliance. Therefore, it is urgently demanded to find a new alternative route of noninjection drug delivery system for SMPA. Methods: Two dry powder inhalation (DPI) formulations of spray-dried SMPA formulation (P1) and spray-dried SMPA-L-leucine formulation (P2) were prepared by spray drying method and their physicochemical properties were assessed by thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, particle size distribution analysis, and in vitro aerodynamic analysis. Moreover, In vitro cytotoxicity of SMPA and P2 was conducted with NR8383 cells. In vivo pharmacokinetics were carried out by Penn-Century endotracheal intubation technique to deliver P2 to the lungs of rats. Results and Conclusions: The moisture content of P1 and P2 were 5.81% ± 0.005%, and 4.08% ± 0.002%, respectively. P1 and P2 were in an amorphous state. Moreover, P1 had slightly corrugated surfaces, whereas P2 exhibited severely corrugated surfaces with invagination due to the presence of L-leucine. In addition, there were more hollow particles with smooth surface in P1 than that in P2. Compared with P1, P2 has shown optimal physical particle size and aerosolization behavior with D (v, 50) of 2.64 ± 0.01 µm and fine particle fraction of 37.55% ± 2.63%. The findings of in vitro cytotoxicity showed that P2 did not inhibit cell viability and could be safe for pulmonary administration. The absolute bioavailability of salvianolic acid B (Sal B) for pulmonary administration was 19.15% ± 7.44%, which is significantly higher than the oral bioavailability of Sal B (<5.56%). In this study, we have shown the feasibleness of pulmonary administration of SMPA in the form of DPIs for systemic delivery to treat cardiovascular diseases.

Brain targeting of Baicalin and Salvianolic acid B combination by OX26 functionalized nanostructured lipid carriers.

In order to deliver Salvianolic acid B (Sal B) and Baicalin (BA) to the brain tissue to repair neuron damage and improve cerebral ischemia-reperfusion injury (IRI), in our previous study, a nanostructured lipid carrier (NLC) containing BA and Sal B, and modified by the transferrin receptor monoclonal antibody OX26 (OX26-BA/Sal B-NLC) was constructed. The present study is to evaluate its in vitro release behavior, in vitro and in vivo targeting ability, in vitro pharmacodynamics and brain pharmacokinetics. The results showed that the release mechanism of the formulation was in line with the Weibull model release equation. The in-vitro and in-vivo targeting ability study exhibited that OX26 modified formulations was obviously higher than that of non-modified and solution groups. The results of in vitro preliminary study to investigate the protective effect of OX26-BA/Sal B-NLC on oxygen-glucose deprivation/reperfusion injured cells showed that it could decrease the injury. Furthermore, the results of brain microdialysis study showed that the OX26-modified preparation group could significantly increase the content of BA in the brain. In the solution group and the unmodified group, Sal B can only be detected at few time points, while OX26-modified BA/Sal B-NLC could be detected within 4 h. These results indicating that OX26-modified NLC can promote the brain delivery of Sal B and BA combination.

Dimeric c(RGD) peptide conjugated nanostructured lipid carriers for efficient delivery of Gambogic acid to breast cancer.

Background and purpose: Gambogic acid (GA) is a natural compound that exhibited a promising multi-target antitumor activity against several types of cancer. However, the clinical application of this drug is limited due to its poor solubility and low tumor cell-specific delivery. In this study, the monomeric and dimeric Cyclo (Arg-Gly-Asp) c(RGD) tumor targeting peptides (c(RGDfK) and E-[c(RGDfK)2]) were used to modify GA loaded nanostructured lipid carriers (NLC) to reduce the limitations associated with GA and improve its antitumor activity. Methods: GA-NLC was prepared by emulsification and solvent evaporation methods and the surface of the NLC was conjugated with the c(RGD) peptides via an amide bond. The formulations were characterized for particle size, morphology and zeta potential, encapsulation efficiency and drug loading. The in-vitro cytotoxicity and cell uptake studies were conducted using 4T1 cell. Furthermore, the in-vivo antitumor activity and bio-distribution study were performed on female BALB/c nude mice. Results: The c(RGD) peptides modified GA-NLC was successfully prepared with the particles size about 20 nm. The HPLC analysis, FT-IR and 1H-NMR spectra confirmed the successful conjugation of the peptides with the NLC. The in-vitro cytotoxicity study on 4T1 cells revealed that c(RGD) peptides modified GA-NLCs showed significantly higher cytotoxicity at 0.25 and 0.5 µg/mL as compared to unmodified GA-NLC. Furthermore, the cell uptake study demonstrated that better accumulation of E-[c(RGDfK)2] peptides modified NLC in 4T1 cell after 12 h incubation. Moreover, the in-vivo study showed that c(RGD)s functionalized GA-NLC exhibited better accumulation in tumor tissue and tumor growth inhibition. In contrast to the monomeric c(RGD) peptide, the dimeric c(RGD) peptide (E-[c(RGDfK)2]) conjugated GA-NLC showed the improved antitumor activity and tumor targeting ability of GA-NLC. Conclusion: These data provide further support for the potential clinical applications of E-[c(RGDfK)2]-GA-NLC in breast cancer therapy.

Traditional Chinese medicine combined with hepatic targeted drug delivery systems: A new strategy for the treatment of liver diseases.

Liver diseases are clinically common and present a substantial public health issue. Many of the currently available drugs for the treatment of liver diseases suffer from limitations that include low hepatic distribution, lack of target effects, poor in vivo stability and adverse effects on other organs. Consequently, conventional treatment of hepatic diseases is ineffective. TCM is commonly used in the treatment of liver diseases worldwide, particularly in China, and has advantages over conventional therapy. HTDDS can be designed to enhance clinical efficacy in the treatment of liver diseases. We have conducted an extensive review of 335 studies reported since 1964. These included about 166 references involving the treatment of liver diseases with TCM (covering active components of TCM, single TCM and Chinese medicine formulas), 169 reports on HTDDS and background studies on liver-related diseases. Here we review the long history of TCM in the treatment of liver diseases.We have also reviewed the status of studies on active components of TCM using nanotechnology-based targeted delivery systems to provide support for further research and development of TCM-based targeted preparations for the treatment of liver disease.

Quantification of Nineteen Bioactive Components in the Ancient Classical Chinese Medicine Formula of Wen-Dan Decoction and Its Commercial Preparations by UHPLC-QQQ-MS/MS.

A UHPLC-QQQ-MS/MS method was developed to quantify the significant constituents in Wen-Dan Decoction (WDD), a traditional Chinese medicine. Analysis of 19 compounds was conducted on an ACQUITY UPLC® BEH C18 Column (2.1 × 50 mm, 1.7 µm) using elution with a gradient elution of acetonitrile and 0.05% (v/v) formic acid in water. A triple quadrupole mass spectrometer was operated in negative ionization mode and positive ionization mode by multiple reaction monitoring (MRM), respectively. All calibration curves showed acceptable linearity (r ≥ 0.9950). The RSDs of intra- and inter-day precisions of low, mid and high concentrations were ≤ 8.88%. The repeatabilities (RSDs ≤ 7.17%) and stabilities (RSD ≤ 4.79%) of the samples were qualified. The recoveries were found in the range of 93.07 ± 3.86 to 103.98 ± 2.98% with the RSD varying between 1.30 and 7.86%. The final rapid, sensitive, precise, accurate and reliable UHPLC-QQQ-MS/MS method was used for the simultaneous quantification of 19 constituents in WDD and its commercial preparations. The strategy of combining the contents of the 19 chemicals in a daily dose of the WDD preparations with the hierarchical cluster analysis and the 3D principal component analysis was employed to effectively distinguish the WDD preparations provided by the different suppliers, which represents a contribution to the evaluation and control of the quality of WDD (or other decoctions consisting of the same herbs) and the preparations of WDD in other dosage forms such as tablets and granules.

Preparation, optimization and cellular uptake study of tanshinone I nanoemulsion modified with lactoferrin for brain drug delivery.

Tanshinone I (TSI) is one of the bioactive compound obtained from the root of Salvia miltiorrhiza which is a well-known traditional Chinese medicine (TCM) used for the treatment of various diseases. Although TSI possesses several pharmacological effects, it has poor water solubility, blood-brain barrier (BBB) permeability and brain bioavailability. Therefore, in the present study, we developed TSI nanoemulsion (TSI-NE) modified with a brain targeting ligand (Lactoferrin (Lf)) to improve the BBB permeability. Pseudo-ternary phase diagrams were used to optimize the formulation. The optimal TSI-NE and TSI-Lf-NE were prepared and characterized. Finally, the uptake of TSI-Lf-NE by mouse brain microvascular endothelial cell line (bEnd.3 cells) was assessed using Coumarin-6 as a fluorescent probe. The results of the study showed that the stable optimal formulation of O/W nanoemulsion was successfully developed and modified with Lf. The cellular uptake study has shown that the fluorescence intensity (FI) increased with time over the incubation period. The FI at all time intervals increased in the following order: Coumarin-6-Solution＜Coumarin-6-NE＜Coumarin-6-Lf-NE. The results suggest that the BBB permeability of Coumarin-6-Lf-NE was better than those of Coumarin-6-NE and Coumarin-6 solution. Lf modified nanoemulsion has great potential for improving the brain delivery of TSI.

Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment.

Cancer is a major public health problem, and is now the world's leading cause of death. Traditional Chinese medicine (TCM)-combination therapy is a new treatment approach and a vital therapeutic strategy for cancer, as it exhibits promising antitumor potential. Nano-targeted drug-delivery systems have remarkable advantages and allow the development of TCM-combination therapies by systematically controlling drug release and delivering drugs to solid tumors. In this review, the anticancer activity of TCM compounds is introduced. The combined use of TCM for antitumor treatment is analyzed and summarized. These combination therapies, using a single nanocarrier system, namely codelivery, are analyzed, issues that require attention are determined, and future perspectives are identified. We carried out a systematic review of >280 studies published in PubMed since 1985 (no patents involved), in order to provide a few basic considerations in terms of the design principles and management of targeted nanotechnology-based TCM-combination therapies.

Research progress of in-situ gelling ophthalmic drug delivery system.

Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (<5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.

A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein.

Baicalein (BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide (BE-NCT) nano-cocrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0 -  t of BE-NCT nano-cocrystals (6.02-fold) was significantly higher than BE coarse powder (1-fold), BE-NCT cocrystals (2.87-fold) and BE nanocrystals (3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BE-NCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations. Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.

Cell penetrating peptides functionalized gambogic acid-nanostructured lipid carrier for cancer treatment.

Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR). The GA-NLC was prepared by emulsification and solvent evaporation method and coupled with cRGD, RGERPPR, and combination cRGD and RGERPPR to form GA-NLC-cRGD, GA-NLC-RGE, and GA-NLC-cRGD/RGE, respectively. The formulations were characterized by their particle size and morphology, zeta potential, encapsulation efficiency, and differential scanning calorimetry. In vitro cytotoxicity and cellular uptake study of the formulations were performed against breast cancer cell (MDA-MB-231). Furthermore, in vivo biodistribution and antitumor activity of the formulations were determined by in vivo imaging and in tumor-bearing nude mice, respectively. The result of in vitro cytotoxicity study showed that GA-NLC-RGE exhibited a significantly higher cytotoxicity on MDA-MB-231 as compared with GA-NLC and GA-Sol. Similarly, RGE-Cou-6-NLC showed remarkably higher uptake by the cells than other NLCs over the incubation period. The in vivo imaging study has demonstrated that among the formulations, the RGE-decorated DiR-NLC were more accumulated in the tumor site. The in vivo antitumor activity revealed that RGE-GA-NLC inhibits the tumor growth more efficiently than other formulations. In conclusion, RGERPPR has a potential as an effective carrier in targeting drug delivery of anticancer agents.

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers.

Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.