Pharmaceutical Nanotechnology - Volume 9, Issue 5, 2021

Abstract: Alzheimer's disease (AD) is a neurological disease that affects many of the world's rapidly ageing population. In the etiology of Alzheimer’s disease (AD), the involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Various drugs have been proposed to prevent and treat AD, but delivering these therapeutic agents to the brain is difficult. Over the last decade, nanoparticle-mediated drug delivery represents one promising strategy to increase the CNS penetration of several therapeutic moieties successfully. Different nanocarriers are being investigated to treat and diagnose AD. NTDDS (nanotechnology-based drug delivery systems) can be used in various methods to improve patient compliance and treatment outcomes. However, literature analysis revealed that clinical activities, such as NTDDS application in Alzheimer's disease research lag behind despite extensive research. This review gives an account of the BBB and discusses the literature on some drugs, which are successfully encapsulated as nanoparticles for a future therapeutic approach. It also emphasizes the current clinical studies for Alzheimer's disease therapy.

Background: Portage of therapeutic agents directly to the skin (cutaneous/dermal delivery) is the preferable approach in mitigating and curing a variety of skin manifestations, including itching, eczema, acne, psoriasis keratinization, and skin cancer. Dermal delivery reduces side effects associated with systemic therapy and allows maximum utilization of the available doses. Invasomes are the next generation of liposomes with greater flexibility, elasticity, and permeability through the skin than liposomes and ethosomes. Objective: This review article highlights various aspects of invasomes, including the structure and composition of invasomes, methods of preparation of invasomes, the mechanism involved in better penetration through the skin, key parameters to be considered for effective permeation, therapeutic applications of invasomes as novel drug delivery systems, and future development and challenges. Methods: The authors have reviewed various primary and secondary sources, including PUBMED, SCIENCE DIRECT, INFORMA, and patents.com, to collect information on various aspects of invasomes. Results and Conclusion: Invasomes are novel vesicular drug delivery systems that have been used for dermal delivery of drugs for various therapeutic applications. These novel carriers have great ability, and their properties can be highly modulated by varying their composition and concentration of terpenes. Based on all the research reports gathered, it is well proven that these systems have a much higher potential for delivering drugs for skin manifestations and could expand the opportunities for treating various dermatological issues, increasing day by day.

Abstract: Repaglinide is an antidiabetic drug that works by stimulating insulin secretion from pancreatic beta cells. Repaglinide is practically insoluble in water with a water solubility of 34 μg/mL at 37°C, and it has a high absorption rate from the gastrointestinal tract following oral administration since the log P value of repaglinide is 3.97. The low aqueous solubility and the high permeability of repaglinide represent a typical behavior for drugs that belong to class II Biopharmaceutical Classification System (BCS II). Managing type-2 diabetes mellitus with repaglinide is considered a burdensome therapy, as it requires frequent dosing of repaglinide before each meal to maintain its therapeutic plasma concentration due to its short plasma half-life of approximately one hour. Hence the present review aims to discuss thoroughly the various approaches investigated in recent years to develop drug delivery systems that improve oral delivery of repaglinide, including nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, sustained-release hydrophilic matrix, floating microspheres, and nanocomposites.

Introduction: Mikania micrantha has been traditionally used for wound dressings and to promote the healing of sores. This is due to the content of alkaloids and terpenoids/steroids compounds. Hyperglycemia is a good medium for bacterial growth that inhibits the wound healing process. Purpose: This study aimed to determine the wound healing of nanogels containing MMLE in hyperglycemic rats as a model for diabetic wounds. Methods: Mikania micrantha leaves were extracted with the maceration method using 96% ethanol in 5 days. Carbopol 940 was used as the gelling agent. The parameters observed during the physical testing of nanogels were organoleptic, homogeneity, pH, and size of the particle. Antibacterial activity was tested on Staphylococcus aureus, Staphylococcus epidermis, and Escherichia coli. Moreover, wound healing activity was tested in hyperglycemic rats after observing for 14 days. Diabetic wound healing was treated with 4 groups (P1, P2, K1, K2). Data were analyzed using SPSS. Results: Nanogel showed homogeneity, dark green color, transparency, pH 6.1± 0.1, and particle size range in 255-456 nm. The inhibition zones of antibacterial testing, i.e., Staphylococcus aureus, Staphylococcus epidermis, and Escherichia coli, were 10.57 ± 0.26 mm, 9.73 ± 0.21 mm, and 8.4 ± 0.1 mm. The percentage of diabetic wound healing was in the range of 92.79±3.81% to 94.08 ± 2.33% for 14 days of observation. Conclusion: MMLE nanogels have the potential as a treatment for diabetic wound healing.

Background: Presently reported methods for purification of liposomal formulations at laboratory scale have drawbacks of adversely affecting critical quality attributes (CQAs) of liposomes such as particle size, PDI, drug entrapment efficiency, etc., and are also not amenable for large scale processing. Objective: The present study was aimed to explore stirred cell ultrafiltration technique as a novel liposome purification method for removal of unentrapped free drug and excess external aqueous fluid, maintaining the physical integrity of liposomes. Methods: Purification of brimonidine loaded liposomes (model formulation) was performed by stirred cell ultrafiltration method, and its functional performance and impact on liposomal particle size, PDI, and entrapment efficiency were compared with two widely used laboratory scale methods, i.e., ultracentrifugation and centrifugal ultrafiltration. Results: The novel stirred cell ultrafiltration method demonstrated liposomal purification within ~30 min with complete liposomal recovery showing minimal processing impact, i.e., #130;0.25 fold rise in particle size, ~0.5 fold rise in PDI, and ~4% loss in % entrapment efficiency, respectively. Whereas ultracentrifugation and centrifugal ultrafiltration methods resulted in ~4 fold and #131;2 fold rise in particle size, #131;10 fold and #131;5 fold rise in PDI, and #131;25% and ~6% loss in entrapment efficiency, respectively. Conclusion: The unique and product-friendly operational features of stirred cell ultrafiltration method demonstrated simple, rapid, and efficient liposomal purification without affecting CQAs of liposomal vesicles. This method was also evidently found to be product-friendly, rugged, versatile, and scalable up to large production batch processing, overcoming major drawbacks of presently used methods.

Aim: This study was designed to prepare and evaluate cefixime-loaded nanoparticles containing low molecular weight chitosan films for the enhanced topical treatment of periodontitis. Methods: To fabricate the enhanced antimicrobial films, a nanoprecipitation method for cefixime nanoparticles followed by a solvent evaporation method for these nanoparticles loaded films were adopted in this study. Nine batches of nanoparticles (NPs) with different concentrations of ethyl cellulose and polyvinyl alcohol were prepared and evaluated. Furthermore, nine batches of optimized NPs loaded films with different concentrations of low molecular weight chitosan and glycerol were fabricated and evaluated. Optimized NPs loaded films were assessed for their antimicrobial activity against the periodontitis patient’s saliva samples. Results: The FT-IR spectroscopy and XRD study revealed that there was no interaction between the drug and all other excipients and the drug remained amorphous form in chitosan film. The SEM study revealed that the prepared NPs were spherical in shape and uniformly distributed in chitosan film. In vitro drug release study revealed the NPs have a sustained release profile up to 8 days and NPs loaded films have up to 11 days. The conventional marketed mouth wash shows a low inhibition zone of 5.70 ± 0.043 mm, whereas NPs loaded film shows a higher inhibition zone of 6.72 ± 0.063 mm against periodontal microorganisms present in the patient’s saliva. The stability study revealed that the optimized NPs loaded film shows no dramatic change in drug release profile and folding endurance after six months. Conclusion: This present study highlights the possible usage of cefixime NPs loaded films in enhanced periodontal treatment.

Background: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. Objectives: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. Methods: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. Results: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R²#131; 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 μg L^-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient’s urine samples. Conclusion: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.