Applications of lipid-based nanocarriers for parenteral drug delivery

This review describes the use of Lipid-based Nanocarriers (LNCs) for the parenteral delivery of pharmaceutical actives. Firstly, the two generation of LNCs such as ‘‘solid lipid nanoparticles’’ (SLNs) and ‘‘nanostructured lipid carriers’’ (NLCs) are explained in term of preparation, characterization and stability. Although the use of LNCs through parenteral administration has shown many benefits, their use is limited by opsonization, an immune process that causes their short half-life (3-5 min). Therefore, many strategies are discussed to realize “stealth” systems suitable for parenteral administration. Successfully, the requirements and applications of parenteral lipid nanoparticles are reviewed for the delivery of natural compounds, synthetic drugs and genetic materials. In the last period, the latter application has been a remarkable interest due to the numerous benefits of mRNA vaccines to fight the Covid-19 pandemic.

An Extensive Review on Chitosan as Versatile Material for Pharmaceutical and Biomedical Application

Chitosan is a polysaccharide and is derived from chitin. Chitosan every now and then referred to as a soluble chitin. chitosan is strongly basic polysaccharide. chitosan shows physiochemical and biological properties. This review presents the common source for chitosan manufacturing that is crabs and shrimp. According to researchers it is just a fat inhibitor. some of the application of chitosan in pharmaceutics/drug delivery and in biomedical field are also highlighted. Chitosan act as a diluent, as mucoadhesive excipient, as permeation enhancer, in vaccines delivery, as parenteral delivery, chitosan as food additive, cosmetics industry. chitosan also has a number of medicinal benefits. Chitosan is employed in a variety of applications because it is soluble in acidic aqueous conditions (food, cosmetics, biomedical and pharmaceutical applications). We give a quick overview of the chemical modifications of chitosan, a field in which a number of syntheses have been proposed but not yet realised on a large scale. This review focuses on current articles on these materials' high-value-added applications in medicine and cosmetics.

Development and Evaluation of Indomethacin Parenteral Delivery of Microspheres for the Treatment of Gout

Gout is a disease caused by the deposition of monosodium urate (MSU) crystals in tissue such as cartilage, synovial membranes, bones and skin which causes inflammation in the synovial tissue. Indomethacin is first line of drug used as NSAID for the treatment of Gout. The aim of this study was to encapsulate Indomethacin in ethyl cellulose microspheres and compare the efficiency of the formulated Indomethacin microspheres with the Marketed formulation. Indomethacin microspheres were prepared by solvent evaporation method. FTIR studies revealed there was no significant interaction between the drug and polymer. Preformulation studies gave satisfactory results. SEM studies showed a spherical smooth microsphere average size of 10.4±3.04. The percentage entrapment efficiency and percentage drug release after 10 hours was found to be 82.97±1.6 % and 52.04±0.58 % respectively. The therapeutic effect of the Indomethacin microspheres was evaluated by the swelling of knee joints, joint range of motion and histologic analysis of MSU induced rat model. The prepared indomethacin microspheres showed effective prolong in the retention time of the drug in the intra articular cavity to 30 d which is more than that of the marketed formulation. Intra- articular injection of Indomethacin microspheres efficiently relieved inflammatory symptoms such as swelling index, joint range motion and suppressed inflammatory cell infiltration than the marketed formulation. Thus intra-articular injection of Indomethacin loaded microspheres proved to be a promising therapeutic method in the treatment of Gout. Keywords: Gout, indomethacin, ethyl cellulose, microspheres, inta-articular

Immune Responses and Efficacy of Brucella Abortus Strain RB51 in Bison After Delivery in a Dry Dart Formulation or by Parenteral Inoculation

Bison (Bison bison) heifer calves (n = 32) were randomly assigned to control or vaccination with 1010 colony-forming units of Brucella abortus strain RB51 (RB51) vaccine by single or boostered parenteral delivery, or by surgical implantation of a dry dart formulation (n = 8/trt). Serum and/or peripheral blood mononuclear cells (PBMC) were obtained at 0, 4, 8, 13, 16, 21, and 24 wks after initial vaccination and at 0, 4, 8, 12, 15, 22, and 27 wks after booster vaccination to characterize humoral and cellular immune responses to RB51. Bison in both RB51 vaccination treatments demonstrated greater (P < 0.0001) serum humoral responses when compared to non-vaccinates, with parenteral vaccinates demonstrating greater (P < 0.01) responses when compared to mean responses of bison inoculated with the dry dart. Only the booster vaccinated treatment demonstrated greater (P < 0.0001) humoral responses than control bison in samples collected after re-inoculation. At 4, 8, 12, 16, and 24 wks after initial vaccination, PBMC from parenteral RB51 vaccinates demonstrated greater proliferative responses to RB51 when compared to responses of control animals. In comparison, bison inoculated with the RB51 dry dart did not demonstrate greater (P > 0.05) proliferative responses when compared to responses of non-vaccinates. Bison were pasture bred and pregnant animals experimentally challenged in mid-gestation with 107 CFU of B. abortus strain 2,308. Bison in parenteral vaccination treatments had reduced (P < 0.05) abortions and infection in uterine and fetal samples as compared to non-vaccinated bison, with booster vaccinates tending to have the lowest colonization (CFU/gm) in tissues. In comparison, the dry dart formulation did reduce abortion (P < 0.05) but not infection (P > 0.05) in most tissues when compared to non-vaccinated bison. The results of this study reaffirm the efficacy of boostered parenteral vaccination of bison with RB51 in preventing brucellosis. Our data also suggests that the novel dry dart RB51 formulation does not induce sufficient efficacy in bison after a single inoculation.

Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.

Trends in liposomal nanocarrier strategies for the oral delivery of biologics

The number of approved macromolecular drugs such as peptides, proteins and antibodies steadily increases. Since drugs with high molecular weight are commonly not suitable for oral delivery, research on carrier strategies enabling oral administration is of vital interest. In past decades, nanocarriers, in particular liposomes, have been exhaustively investigated as oral drug-delivery platform. Despite their successful application as parenteral delivery vehicles, liposomes have up to date not succeeded for oral administration. However, a plenitude of approaches aiming to increase the oral bioavailability of macromolecular drugs administered by liposomal formulations has been published. Here, we summarize the strategies published in the last 10 years (vaccine strategies excluded) with a main focus on strategies proven efficient in animal models.

Bioadhesive polymers, permeation enhancers and types of dosage forms for buccal drug delivery

The buccal delivery is defined as the drug administration through the mucosal membranes lining the cheeks (buccal mucosa). The main impediment to the use of many hydrophilic macromolecular drugs as potential therapeutic agents is their inadequate and erratic oral absorption. Based on our current understanding of biochemical and physiological aspects of absorption and metabolism of many biotechnologically produced drugs, they cannot be delivered effectively through the conventional oral route. Because after oral administration many drugs are subjected to pre-systemic clearance extensive in the liver, which often leads to a lack of significant correlation between membrane permeability, absorption and bioavailability. Difficulties associated with the parenteral delivery and poor oral bioavailability provided the impetus for exploring alternative routes for the delivery of such drugs. This review covers the advantages, disadvantages of buccal delivery, drug and excipient selection especially bioadhesive polymers and permeation enhancers, and further a list of drugs developed as various dosage forms for buccal route of administration. Keywords: Buccal delivery, bioadhesive/mucoadhesive, permeation enhancer, dosage forms.

Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals

During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.