Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid using Taguchi Design.

BACKGROUND: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and lifethreatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. OBJECTIVE: The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. METHODS: SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and in vivo antibacterial activity were conducted. RESULTS: The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. CONCLUSION: Ex vivo studies ascertain the presence of the drug at the desired site and improve therapy. In vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

A Comprehensive Review on Current Treatments and Challenges Involved in the Treatment of Ovarian Cancer.

Ovarian cancer (OC) is the second most common gynaecological malignancy. It typically affects females over the age of 50, and since 75% of cases are only discovered at stage III or IV, this is a sign of a poor diagnosis. Despite intraperitoneal chemotherapy's chemosensitivity, most patients relapse and face death. Early detection is difficult, but treatment is also difficult due to the route of administration, resistance to therapy with recurrence, and the need for precise cancer targeting to minimize cytotoxicity and adverse effects. On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic medications has manifested resistance, a condition known as multidrug resistance (MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance. Different pathways contribute to MDR development in ovarian cancer; however, usually, pump and non-pump mechanisms are involved. Striking cancerous cells from several angles is important to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes to hit the pump mechanism. Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery, the current review attempts to explain the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery into the intracellular compartment before optimizing intra-tumour distribution. Other novel treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic efficacy.

Challenges and Therapeutic Approaches for the Protein Delivery System: A Review.

The protein delivery system is one of the innovative or novel drug delivery systems in the present era. Proteins play an indispensable role in our body and are mainly found in every part, like tissue and cells of our body. It also controls various functions, such as maintaining our tissue, transportation, muscle recovery, enzyme production and acting as an energy source for our body. Protein therapeutics have big future perspectives, and their use in the treatment of a wide range of serious diseases has transformed the delivery system in the pharmaceutical and biotechnology industries. The chief advantage of protein delivery is that it can be delivered directly to the systemic circulation. So far, parenteral routes, such as intravenous, intramuscular, and subcutaneous, are the most often used method of administering protein drugs. Alternative routes like buccal, oral, pulmonary, transdermal, nasal, and ocular routes have also shown a remarkable success rate. However, as with all other types of delivery, here, several challenges are posed due to the presence of various barriers, such as the enzymatic barrier, intestinal epithelial barrier, capillary endothelial barrier, and blood-brain barrier. There are several approaches that have been explored to overcome these barriers, such as chemical modification, enzymatic inhibitors, penetration enhancers, and mucoadhesive polymers. This review article discusses the protein, its functions, routes of administration, challenges, and strategies to achieve ultimate formulation goals. Recent advancements like the protein Pegylation method and Depofoam technology are another highlight of the article.

Vaccines: An Important Tool for Infectious Disease.

Vaccines are usually regarded as one of the most important tools in the battle against infectious diseases. Even though currently accessible vaccinations are an incredible success story in contemporary medicine and have had a significant impact on global morbidity and death rates, it is evident that current vaccine delivery approaches need to be improved. To allow the successful creation of vaccinations against contagious diseases that have proven challenging to manage with conventional procedures, improvements are necessary. Improvements could include the introduction of innovative injectable adjuvants or novel delivery methods, such as mucosal immunization. Protection against infections that infect mucosal areas may necessitate mucosal delivery. Alternatively, innovative techniques for delivery, such as intradermal administration using self-administrable devices or the use of microneedle technology to bypass the stratum corneum's skin penetration barrier and aid in the transport of antigens, could be utilized to increase vaccine compliance. Needle-free delivery systems are of particular relevance for safer mass immunization programs, as they would prevent problems caused by needles reuse in several regions of the world, as well as needle-stick accidents. Based on this information, future vaccine development will mainly concentrate on rational antigen, adjuvant, and, most importantly, delivery mechanism design, resulting in new and improved vaccinations. In addition, this study discusses the current state and prospects of vaccine delivery via a variety of channels, including non- or minimally invasive approaches.

Development, optimization and evaluation of solid lipid nanoparticles of Celecoxib.

BACKGROUND: As indicated by the biopharmaceutical classification system, Celecoxib is a class II moiety. Many endeavors have been made to improve its solubility and consequently its dissolution rate, thus enhancing its overall bioavailability. In the present investigation, the nano-lipid technology was exploited to control the release of celecoxib (CXB) to overcome its dissolution problem. Solid lipid nanoparticles (SLNs) have a small particle size (50-1000 nm) that results in a large surface area-to-volume ratio, which further enhances the contact between the drug and the dissolution medium. This leads to improved drug release and absorption. Moreover, SLNs can solubilize hydrophobic drugs within the lipid matrix, increasing their effective solubility and facilitating their dissolution in an aqueous environment. AIM AND OBJECTIVE: The objective of the study was to enhance the solubility and bioavailability of a BCS Class-II drug-celecoxib formulating it as solid lipid nanoparticles. In order to overcome all its limitations, solid lipid nanoparticles of Celecoxib were developed, optimized, and evaluated for in-vitro and in-vivo parameters. METHODS: The CXB loaded-SLNs were prepared by solvent emulsification-diffusion technique. SLN was characterized using Fourier transform infra spectroscopy (FTIR) and evaluated for entrapment efficiency, drug loading, particle size, Polydispersity index (PDI), zeta potential, In-vitro release studies as well as in- vivoanti-inflammatory studies using rat paw edema method. The SLN formulations were optimized by central composite design (Design Expert 11- trial version). RESULTS: On the basis of outcomes of CCD the optimized formulation OF1 was selected as a desirable formulation. Its particle size, PDI, and zeta potential were found to be 314 nm, 0.204, and -18.73 respectively. It exhibited high entrapment efficiency (79±0.18 %) and drug loading (44.38±0.21 %). In-vitro release studies of the optimized formulation displayed the Korsemeyer-Peppas model with a maximum drug release of 89.42 ±0.12 % in 24 h. In-vivo studies also revealed that OF1 formulation reduced the rat paw volume to a minimum (1±0.32) in 24 h when compared to pure API (2±0.62) and marketed preparation (2±0.42). CONCLUSION: The results revealed that in-vitro release studies of optimized formulation exhibited a sustained drug release delivery. In-vivo anti-inflammatory studies proved that the CXB-loaded SLNs enhance the oral bioavailability more than pure API.

Nanostructured Lipid Carriers: A Groundbreaking Approach for Transdermal Drug Delivery.

Nanostructured lipid carriers (NLCs) are novel pharmaceutical formulations which are composed of physiological and biocompatible lipids, surfactants and co-surfactants. Over time, as a second generation lipid nanocarrier NLC has emerged as an alternative to first generation nanoparticles. This review article highlights the structure, composition, various formulation methodologies, and characterization of NLCs which are prerequisites in formulating a stable drug delivery system. NLCs hold an eminent potential in pharmaceuticals and cosmetics market because of extensive beneficial effects like skin hydration, occlusion, enhanced bioavailability, and skin targeting. This article aims to evoke an interest in the current state of art NLC by discussing their promising assistance in topical drug delivery system. The key attributes of NLC that make them a promising drug delivery system are ease of preparation, biocompatibility, the feasibility of scale up, non-toxicity, improved drug loading, and stability.

Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.