Pharmaceutical Nanotechnology - Volume 8, Issue 6, 2020

Background: Coronavirus has become a life-threatening disease and it is caused by severe acute respiratory syndrome (SARS). This new strain of coronavirus is not completely understood and to date, there is no treatment for coronavirus. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. In the meantime, guidelines of the ministry of AYUSH (Ayurveda, yoga, unani, siddha and homoepathy) include a traditional medicinal treatment for flu and fever and also recommended to boost immunity to prevent the spread of coronavirus. It is not possible to find which essential oil will offer the best level of protection. However, it is likely to assume that some essential oils are likely to offer a measurable level of defense in the same way they do with many other known viruses. Methods: Literature relevant to various essential oils having antiviral activity has been collected and compiled. Various nanocarriers of essential oils have also been stated. The database was collected using various search engines such as J-Gate, Google Scholar, Sci-Hub, PubMed, ScienceDirect, etc. Results: Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activities and many more. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. Conclusion: Several essential oils possess potent antiviral activity and are characterized by fewer side effects and are safe for human use. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections. Lay Summary: Current COVID-19 era demands traditional treatment for immunity boost up as support therapy. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. Therefore, authors have summarized various essential oils having antiviral activity in current manuscript. Various nanocarriers of essential oils have been reported. Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activity. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections.

Background: The hypothesis is to augment the bioavailability and therapeutic potential of low bioavailable Carvedilol (25-35%) through Nanostructured Lipid Carrier (NLC) loaded Transdermal patch (Nanolipid Transferosomes). Methods: Box-Behnken design was designed to formulate NLC through a hot homogenization technique. About 17 formulations (C1-C17) were formulated by varying the critical material attribute and critical process parameter. Optimization was done based on its critical quality attributes like particle size, zeta potential and entrapment efficiency. Selected NLC (C16) has been fabricated into a transdermal patch through solvent evaporation technique and estimated for thickness, weight variation, moisture content, folding endurance, drug content, in vitro drug release, ex vivo skin permeation studies 48 hrs, in vitro drug release kinetic studies and skin irritation studies. In vivo pharmacokinetics and pharmacodynamic study parameters were compared between carvedilol loaded NLC transdermal patch and a conventional formulation (Coreg CR). Results: NLC (C16) was selected as the best formulation based on desirable, less particle size (201.1 ± 2.02 nm), more zeta potential (-37.2 ± 1.84mV) and maximum entrapment efficiency (87.54 ± 1.84%). Experimental investigations of In vivo dermatopharmacokinetic data shown statistically significant changes (p<0.05) in the parameter (increased AUC0-α, MRT with decreased Cmax, Tmax) when administered through the transdermal patch and on compared to the conventional dosage form. It was observed that there was a significant change with p<0.05 among the pharmacokinetic factors of conventional Carvedilol formulation, Carvedilol NLC and Carvedilol NLC loaded Transdermal patch with a maximum time of peak plasma concentration (Tmax) of 4 hrs, 8 hrs and 8 hrs; maximum peak plasma concentration (Cmax) of 0.258 μg/ml, 0.208 μg/ml and 0.108 μg/ml. Area Under Curve (AUC0-α) was established to be 125.127 μg/ml/h, 132.576 μg/ml.h and 841.032 μg/ml.h. Mean Residence Time (MRT0- α) of the drug was established to be 17 hrs, 19 hrs and 82 hrs, respectively. This data reveals the impact of NLC on the enhancement of bioavailability through a transdermal patch. In vivo pharmacodynamic studies confirm that NLC loaded transdermal patch (Nanolipid Transferosomes) shows a significant control in blood pressure for 48 hrs when compared to the conventional dosage form. Conclusion: This research data concludes that NLC loaded transdermal patch (Nanolipid Transferosomes) was a suitable candidate to enhance the bioavailability of low bioavailable drug-like Carvedilol. Lay Summary: It was inferred from the literature that NLC filled transdermal patches were a novel strategy to increase the solubility and permeability of Carvedilol, which has less bioavailability. It reveals that there was no reproducible preparation for the NLC. It also reveals that the option of formulation and process parameters for the formation of NLC is not clearly justified. On account of this, an uniquely validated and optimized formulation technique was developed for NLC with low soluble and poorly bioavailable carvedilol, tested in Albino wistar rats for enhancement of bioavailability, the same study has been performed and proved.

Background: Sorafenib tosylate (SFN) belongs to the BCS class II drug with low solubility and undergoes first-pass metabolism, which leads to reduced bioavailability of 38%. Objective: The present study aimed at developing SFN SNEDDS to improve their solubility and bioavailability. Methods: Preliminary solubility studies were performed to identify oil, surfactant, and co-surfactant ratios. Pseudo tertiary phase diagram was constructed to select the areas of nanoemulsion based on the monophasic region. A total of 15 formulations of SFN SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. These SNEDDS further characterized for % transmission, content of the drug, and in vitro dissolution analysis. The optimized formulation was analyzed for particle size, Z average, entrapment efficiency, and SEM analysis. Results: Based on the pseudo tertiary phase diagram, acrysol EL 135, kolliphor, and transcutol-P as oil, surfactant, and co-surfactant were selected, respectively. All the formulations were stable with no phase separation and maximum % transmittance of 98.92%. The formulation F15 was selected as an optimized one, based on maximum drug content of 99.89%, with 98.94% drug release within 1 hour and it will be stable for 6 months. From in vivo bioavailability studies, the Cmax of optimized SNEDDS (94.12±2.12ng/ml) is higher than pure SFN suspension (15.32±1.46 ng/ml) and the AUC0-∞ of optimized SNEDDS is also increased by 5 times (512.1±8.54 ng.h/ml) than pure drug (98.75±6.45ng.h/ml), which indicates improved bioavailability of the formulation. Conclusion: SFN loaded SNEDDS could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first-pass metabolism and increased solubility. Lay Summary: Renal cell carcinoma accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States. Sorafenib is a protein kinase inhibitor indicated as a treatment for advanced renal cell carcinoma. The present study aimed at developing Sorafenib SNEDDS to improve their solubility and bioavailability. A total of 15 formulations of Sorafenib SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. Sorafenib loaded SNEDDS could potentially be exploited as a delivery system for increased oral bioavailability by 5 times when comparing with pure drug by minimizing first-pass metabolism and increased solubility.

Background: Nanostructured lipid carriers (NLCs), due to their impressive benefits, have recently been considered in different areas. Besides, NLC loaded with essential oils is attractive for finding more effective antimicrobial products, especially against common bacteria such as Staphylococcus epidermidis (S. epidermidis). Objective: This study aims to prepare and characterize NLCs encapsulated with Punica granatum (P. granatum) seed oil (PGS oil-loaded NLCs) and examine the antimicrobial effect of this combination against S. epidermidis. Methods: PGS oil-loaded NLCs were prepared using a hot melt homogenization method. Later, they were characterized by determining particle size distribution (particle size analyzer), morphology (scanning electron microscopy (SEM)), and zeta potential (surface charge of NLCs). Minimum inhibitory concentrations (MIC) of PGS oil-loaded NLCs were assessed and compared with seed oil emulsion of .P. granatum. against S. epidermidis. Results: PGS oil-loaded NLCs were spherical shaped nanoparticles, with a mean size of 102.10 nm and narrow size distribution (PDI = 0.26). The antibacterial assay showed PGS oil-loaded NLCs to have a higher in vitro antimicrobial activity than seed oil emulsion of P. granatum. Conclusion: To conclude, NLCs may be a favorable carrier to develop new antimicrobial agents. Lay Summary: The lipid nanoparticles such as nanostructured lipid carriers (NLCs) appeared as products first on the cosmetic market. Their advantages help them to be used in different healthcare and cosmetic products. With regard to previous studies, Punica granatum (P. granatum) extract shows antimicrobial and antioxidant properties that could be a valuable natural source against the wide ranges of bacteria. Then, P. granatum seed oil (PGS oil-loaded NLCs) prepared in this study can be used in dental and skin-related materials as a new natural antimicrobial product.

Background: All-trans retinoic acid (ATRA) is widely employed in the treatment of various proliferative and inflammatory diseases. However, its therapeutic efficacy is imperiled due to its poor solubility and stability. Latter was surmounted by its incorporation into a solid matrix of lipidic nanoparticles (SLNs). Methods: ATRA loaded SLNs (ATRA-SLNs) were prepared using a novel microemulsification technique (USPTO 9907758) and an optimal composition and were characterized in terms of morphology, differential scanning calorimetry (DSC), and powder X-ray diffraction studies (PXRD). In vitro release, oral plasma pharmacokinetics (in rats) and stability studies were also done. Results: Rod-shaped ATRA-SLNs could successfully incorporate 3.7 mg/mL of ATRA, increasing its solubility (from 4.7 μg/mL) by 787 times, having an average particle size of 131.30 ± 5.0 nm and polydispersibility of 0.283. PXRD, DSC, and FTIR studies confirmed the formation of SLNs. Assay/total drug content and entrapment efficiency of ATRA-SLNs was 92.50 ± 2.10% and 84.60 ± 3.20% (n=6), respectively, which was maintained even on storage for one year under refrigerated conditions as an aqueous dispersion. In vitro release in 0.01 M phosphate buffer (pH 7.4) with 3% tween 80 was extended 12 times from 2h for free ATRA to 24 h for ATRA-SLNs depicting Korsmeyer Peppas release. Oral administration in rats showed 35.03 times enhanced bioavailability for ATRA-SLNs. Conclusion: Present work reports preparation and evaluation of bioenhanced ATRA-SLNs containing a high concentration of ATRA (>15 times than that reported by others). Latter is attributed to the novel preparation process and intelligent selection of components. Lay Summary: All-trans retinoic acid (ATRA) shows an array of pharmacological activities but its efficacy is limited due to poor solubility, stability and side effects. In present study its solubility and efficacy is improved by 787 and 35.5 times, respectively upon incorporation into solid lipid nanoparticles (ATRA-SLNs). Latter extended its release by 12 times and provided stability for at least a year under refrigeration. A controlled and sustained release will reduce dose related side effects. ATRA-SLNs reported presently can thus be used in treatment /prophylaxis of disorders like cancers, tuberculosis, age related macular degeneration and acne and as an immune-booster.