Current Drug Delivery - Volume 16, Issue 1, 2019

Currently, the most important cause of death is cancer. To treat the cancer there are a number of drugs existing in the market but no drug is found to be completely safe and effective. The toxicity of the drugs is the key problem in the cancer chemotherapy. However, plants and plant derived bioactive molecule have proved safe and effective in the treatment of cancers. Phytochemicals that are found in fruits, vegetables, herbs, and plant extract have been usually used for treating cancer. It has been established that several herbal drug have a strong anticancer activity. However, their poor bioavailability, solubility, and stability have severely restricted their use. These problems can be overcome by incorporating the herbal drug in nanolipolomal vesicles. In last few decades, researcher have used herbal drug loaded nanoliposome for the treatment and management of a variety of cancers. Presently, a number of liposomal formulations are on the market for the treatment of cancer and many more are in pipe line. This review discusses about the tumor microenvironment, targeting mechanism of bioactive phytochemicals to the tumor tissue, background of nanoliposome, and the potential therapeutic applications of different bioactive phytochemicals loaded nanoliposome in cancer therapy.

Among the common myths in the cosmetics industry is the perception that acne only happens to teenagers, and specifically to females. However, acne is neither limited to a specific age, nor to a certain gender, it creates a stressful problem for many people. Many chemical treatments for acne were proven to be successful, but when administered as such, they showed many adverse effects, starting from itching to skin dryness and inflammation. Natural remedies have also been explored for acne treatment, and despite their safety, they suffered many stability problems attributed to their physicochemical properties, creating an obstacle for their topical delivery. Therefore, many nanocarriers were used to deliver those chemical and natural remedies topically to maximize their therapeutic potential in acne treatment. The present review discusses the different nanocarriers which were proven successful in improving the acne lesions, focusing on vesicular, lipidic, and polymeric systems.

Wound infections impose a remarkable clinical challenge that has a considerable influence on morbidity and mortality of patients, influencing the cost of treatment. The unprecedented advancements in molecular biology have come up with new molecular and cellular targets that can be successfully applied to develop smarter therapeutics against diversified categories of wounds such as acute and chronic wounds. However, nanotechnology-based diagnostics and treatments have achieved a new horizon in the arena of wound care due to its ability to deliver a plethora of therapeutics into the target site, and to target the complexity of the normal wound-healing process, cell type specificity, and plethora of regulating molecules as well as pathophysiology of chronic wounds. The emerging concepts of nanobiomaterials such as nanoparticles, nanoemulsion, nanofibrous scaffolds, graphene-based nanocomposites, etc., and nano-sized biomaterials like peptides/proteins, DNA/RNA, oligosaccharides have a vast application in the arena of wound care. Multi-functional, unique nano-wound care formulations have acquired major attention by facilitating the wound healing process. In this review, emphasis has been given to different types of nanomaterials used in external wound healing (chronic cutaneous wound healing); the concepts of basic mechanisms of wound healing process and the promising strategies that can help in the field of wound management.

Background: In this research, MIL-53(Fe) was magnetized and the performance of the magnetized material as a drug delivery system for doxycycline was studied. Objectives: The experiments were designed to load the magnetic delivery compounds with different amount of the drug. Methods: The in vitro release rate of doxycycline from magnetic MIL-53(Fe) with different drug content into saline buffered fluid (SBF, pH=7.4) and phosphate buffered saline (PBS, pH=3) was then studied. Results: The results showed that the releasing process of the drug in PBS media achieved the equilibration within 48h with 98% of releasing efficiency, while the releasing process in SBF media (pH=7.4) was slower and the equilibrium was established within 264 h with the releasing efficiency of 95%. The amount of the released doxycycline from the samples with different drug content was measured at various time intervals. Conclusion: It was concluded that in PBS media after 75 h, 85, 95 and 98% of loaded doxycycline released, respectively, from the sample containing 22, 32 and 35% of the drug. In SBF media, the release was slower and after 350 h, 82, 91 and 95% of loaded doxycycline released from the samples, respectively, containing 22, 32 and 35 % of the drug. The results of this study indicated that by use of drugreleasing profile and selecting appropriate carrier dose, the released amount of the drug into the patient body can be controlled.

Background: Presence of blood brain barrier is one of the major hurdle in drug delivery to brain for the treatment of neurological diseases. Alternative and more effective drug delivery approaches have been investigated for the drug targeting to brain in therapeutic range. Objective: The present investigation was carried out to improve the galantamine bioavailability in brain by intranasal drug delivery through thiolated chitosan nanoparticles and compared to nasal and oral delivery of its solution using pharmacodynamic activity as well as biochemical estimation. Methods: Thiolated chitosan (modified) nanoparticles were fabricated using modified ionic gelation method and intranasal delivery is evaluated by reversal of scopolamine induced amnesia and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain. Scopolamine (0.4 mg/kg, i.p.) was used to induce amnesia. Piracetam (400mg/kg, i.p.) was used as positive control. Mice were treated with galantamine solution (4mg/kg) by oral and nasal route and formulated galantamine nanoparticles (equivalent to 4mg/kg) by intranasal administration for 7 successive days and the results were compared statistically. Results: Intranasal delivery of galantamine loaded thiolated chitosan nanoparticles was found significant (p<0.05) as compared to oral and nasal administration of its solution, by pharmacodynamic study and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain. Conclusion: Significant recovery in amnesia induced mice model by intranasal administration of galantamine loaded thiolated chitosan nanoparticles established the relevance of nose to brain delivery over the conventional oral therapies for the treatment of Alzheimer's disease.

Background: Blood-brain permeability is the primary concern when dealing with the biodistribution of drugs to the brain in neurological diseases. Objective: The purpose of the study is to develop the nanoformulation of Epigallocatechin gallate (EGCG) in order to improve its bioavailability and penetration into the brain. Methods: EGCG loaded Solid Lipid Nanoparticles (SLNs) have been developed using microemulsification method and pharmacological assessments were performed. Results: Surface morphology and micromeritics analysis showed the successful development of EGCG loaded solid lipid nanoparticles with an average size of 162.4 nm and spherical in shape. In vitro release studies indicated a consistent and slow drug release. Pharmacological evaluation of SLN-EGCG demonstrated a significant improvement in cerebral ischemia-induced memory impairment. Conclusion: The results indicate that the EGCG loaded SLNs provide a potential drug delivery system for improved delivery of EGCG to the brain, hence, enhancing its brain bioavailability.

Objective: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. Methods: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. Results: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. Conclusion: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.

Objective: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants. Methods: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release. Results: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM capsules filled with the MLT-loaded nanofibers reached 100% at 6h. Conclusion: These findings suggest that the MLT-loaded nanofibrous mats developed in this study exhibit a promising profile for treating sleep dysfunctions.

Background: Chrysin is a strong inhibitor of breast cancer resistance protein (BCRP) but it is practically insoluble in water. Effective solubilization of chrysin is critical for its pharmaceutical application as an absorption enhancer via inhibition of BCRP-mediated drug efflux. Objective: This study aimed to develop an effective oral formulation of chrysin to improve its in vivo effect as an absorption enhancer. Method: Solid dispersions (SDs) of chrysin were prepared with hydrophilic carriers having surface acting properties and a pH modulator. In vitro and in vivo characterizations were performed to select the optimal SDs of chrysin. Results: SDs with Brij®L4 and aminoclay was most effective in increasing the solubility of chrysin by 13-53 fold at varying drug-carrier ratios. Furthermore, SDs significantly improved the dissolution rate and extent of drug release. SDs (chrysin: Brij®L4: aminoclay=1:3:5) achieved approximately 60% and 83% drug release within 1 h and 8 h, respectively, in aqueous medium, while the dissolution of the untreated chrysin was less than 13%. XRD patterns indicated the amorphous state of chrysin in SDs. The SD formulation was effective in improving the bioavailability of topotecan, a BCRP substrate in rats. Following oral administration of topotecan with the SDs of chrysin, the Cmax and AUC of topotecan was enhanced by approximately 2.6- and 2-fold, respectively, while the untreated chrysin had no effect. Conclusion: The SD formulation of chrysin with Brij®L4 and aminoclay appeared to be promising in improving the dissolution of chrysin and enhancing its in vivo effect as an absorption enhancer.