Exploring the synergistic behavior of paclitaxel and vorinostat upon co-loading in albumin nanoparticles for breast cancer management.

Breast cancer is challenging to treat accompanied with poor clinical outcomes. Paclitaxel (PTX) is a first-line chemotherapeutic agent, but possesses limitations due to side effects, high dose, non-specific tissue distribution, and drug resistance. An epigenetic modulator, vorinostat (VOR) is known to enhance PTX efficacy and therefore to resolve the issues of conventional PTX formulations, we designed PTX- and VOR-bound albumin nanoparticles (PTX-VOR-BSA-NPs) using antisolvent precipitation technique where albumin is used as a carrier and a targeting agent. The PTX-VOR-BSA-NPs were of 140 nm size, polydispersity index around 0.18, and about 78% and 68% of entrapment efficiency for PTX and VOR, respectively. A bi-pattern release of both PTX and VOR was observed from PTX-VOR-BSA-NPs with a burst release for 2 h succeeded by sustained release until 24 h. A significantly lower %cell viability was observed in MCF-7 cell lines, while efficient cellular drug uptake was found in MDA-MB-231 cells. Furthermore, a greater apoptotic index was found compared to free PTX and VOR because of the synergistic activity of these drugs. The PTX-VOR-BSA-NPs also showcased superior pharmacokinetic profile and noteworthy reduction in the tumor volume compared to Intaxel in 4T1 cell line-induced breast tumor model. Further, the NPs showed similar levels of toxicity biomarkers as that of control. Overall, the developed PTX-VOR-BSA-NPs were found to have less toxicity and more effectiveness compared to the marketed formulation, thus affirming the generation of a potent as well as and safe product.

Recent advances in lipid-based long-acting injectable depot formulations.

Long-acting injectable (LAIs) delivery systems sustain the drug therapeutic action in the body, resulting in reduced dosage regimen, toxicity, and improved patient compliance. Lipid-based depots are biocompatible, provide extended drug release, and improve drug stability, making them suitable for systemic and localized treatment of various chronic ailments, including psychosis, diabetes, hormonal disorders, arthritis, ocular diseases, and cancer. These depots include oil solutions, suspensions, oleogels, liquid crystalline systems, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, phospholipid phase separation gel, vesicular phospholipid gel etc. This review summarizes recent advancements in lipid-based LAIs for delivering small and macromolecules, and their potential in managing chronic diseases. It also provides an overview of the lipid depots available in market or clinical phase, as well as patents for lipid-based LAIs. Furthermore, this review critically discusses the current scenario of using in vitro release methods to establish IVIVC and highlights the challenges involved in developing lipid-based LAIs.

Unfolding the Potency of Adenosine in Targeting Triple Negative Breast Cancer via Paclitaxel-Incorporated pH-Responsive Stealth Liposomes.

Triple-negative breast cancer (TNBC) belongs to the category of the most destructive forms of breast cancer. Being a highly potent chemotherapeutic agent, paclitaxel (PTX) is extensively utilized in the management of various cancers. Commercially available PTX formulations contain non-targeted drug carriers that result in low antitumor activity because of non-specific tissue distribution. Thus, to resolve this issue, we designed PTX-loaded pH-sensitive liposomes (pH Lipos) in the present investigation and used adenosine (ADN) as a targeting ligand. Further, d-α-tocopheryl polyethylene glycol succinate (TPGS) was incorporated into the liposomes to impart a stealth effect to the system. For the development of these pH Lipos, different conjugates were synthesized (ADN-CHEMS and TPGS-ADN) and further utilized for the preparation of ADN-PEG-pH Lipo and ADN-pH Lipo by a thin-film hydration method. DOPE:HSPC:CHEMS:cholesterol at a molar ratio of 3:3:2:2 was selected for the preparation of pH-Lipo possessing 7.5% w/w drug loading. They showed a particle size below 140 nm, a PDI below 0.205, and a % EE greater than 60%. All of the pH Lipos displayed a biphasic pattern of PTX release at pH 7.4 and 5.5. However, the percent drug release at pH 5.5 was substantially greater because of the pH-sensitive nature of the liposomes. The MDA MB 231 and 4T1 cell lines depicted improvement in the qualitative as well as quantitative cellular uptake of PTX ADN-PEG-pH Lipo with a substantial decrease in the IC50 value. Moreover, a higher apoptotic index was observed with pH Lipo compared to free PTX. PTX ADN-PEG-pH Lipo revealed a 3.98- and 3.41-fold rise in the AUC and t1/2 values of PTX compared to Intaxel, respectively. Overall, characteristic decreases in tumor volume and serum toxicity marker levels were observed, which confirmed the development of an efficient and safe formulation.

Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics for the treatment of psoriasis.

INTRODUCTION: Psoriasis is an auto-immune inflammatory skin disease affecting people worldwide. Its topical therapy via different nanoformulations prevents the long-term side-effects of conventional formulations. Nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), pose extra benefits in topical drug delivery due to their lipid constituents. Although both natural and synthetic anti-psoriatic drugs have been successfully incorporated in these nanoformulations, yet further studies including dual drug-loadings are being carried out for assessing their efficacy. AREAS COVERED: This review aims at describing the different aspects of SLNs and NLCs in psoriasis, including their skin permeation behavior and the various drug molecules incorporated. The recent studies with single- and dual drug-loaded SLNs and NLCs have also been discussed in the review. EXPERT OPINION: SLNs and NLCs have been very effective in mitigating psoriasis when compared to commercial formulations. They have also shown promising results when loaded with two drugs, thus overcoming drawbacks of traditional combination therapy. Therefore, various drug/antibody/siRNA combinations can be selected in the upcoming research works to evaluate their synergistic performance against psoriasis. However, the conclusions drawn so far are only based on the pre-clinical studies and hence further investigations are required to obtain their clinical trial outcomes.

Nanoparticle-Based Drug Delivery System: The Magic Bullet for the Treatment of Chronic Pulmonary Diseases.

Chronic pulmonary diseases encompass different persistent and lethal diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), asthma, and lung cancers that affect millions of people globally. Traditional pharmacotherapeutic treatment approaches (i.e., bronchodilators, corticosteroids, chemotherapeutics, peptide-based agents, etc.) are not satisfactory to cure or impede diseases. With the advent of nanotechnology, drug delivery to an intended site is still difficult, but the nanoparticle's physicochemical properties can accomplish targeted therapeutic delivery. Based on their surface, size, density, and physical-chemical properties, nanoparticles have demonstrated enhanced pharmacokinetics of actives, achieving the spotlight in the drug delivery research field. In this review, the authors have highlighted different nanoparticle-based therapeutic delivery approaches to treat chronic pulmonary diseases along with the preparation techniques. The authors have remarked the nanosuspension delivery via nebulization and dry powder carrier is further effective in the lung delivery system since the particles released from these systems are innumerable to composite nanoparticles. The authors have also outlined the inhaled particle's toxicity, patented nanoparticle-based pulmonary formulations, and commercial pulmonary drug delivery devices (PDD) in other sections. Recently advanced formulations employing nanoparticles as therapeutic carriers for the efficient treatment of chronic pulmonary diseases are also canvassed.

Application of Design of Experiments® Approach-Driven Artificial Intelligence and Machine Learning for Systematic Optimization of Reverse Phase High Performance Liquid Chromatography Method to Analyze Simultaneously Two Drugs (Cyclosporin A and Etodolac) in Solution, Human Plasma, Nanocapsules, and Emulsions.

The objectives of current investigation are (1) to find out wavelength of maximum absorbance (λmax) for combined cyclosporin A and etodolac solution followed by selection of mobile phase suitable for the RP-HPLC method, (2) to define analytical target profile and critical analytical attributes (CAAs) for the analytical quality by design, (3) to screen critical method parameters with the help of full factorial design followed by optimization with face-centered central composite design (CCD) approach-driven artificial neural network (ANN)-linked with the Levenberg-Marquardt (LM) algorithm for finding the RP-HPLC conditions, (4) to perform validation of analytical procedures (trueness, linearity, precision, robustness, specificity and sensitivity) using combined drug solution, and (5) to determine drug entrapment efficiency value in dual drug-loaded nanocapsules/emulsions, percentage recovery value in human plasma spiked with two drugs and solution state stability analysis at different stress conditions for substantiating the double-stage systematically optimized RP-HPLC method conditions. Through isobestic point and scouting step, 205 nm and ACN:H2O mixture (74:26) were selected respectively as the λmax and mobile phase. The ANN topology (3:10:4) indicating the input, hidden and output layers were generated by taking the 20 trials produced from the face-centered CCD model. The ANN-linked LM model produced minimal differences between predicted and observed values of output parameters (or CAAs), low mean squared error and higher correlation coefficient values in comparison to the respective values produced by face-centered CCD model. The optimized RP-HPLC method could be applied to analyze two drugs concurrently in different formulations, human plasma and solution state stability checking.

Systematic Optimization, In Vitro Drug Release, and Preliminary Nonclinical Toxicity Assessment of Nonphospholipid-Based Topical Ophthalmic Emulsions Containing 0.05 or 0.1% w/w Cyclosporin A for Dry-Eye Syndrome Management.

The objectives of the present investigations are (1) to envisage a risk assessment plan for nonphospholipid-based topical ophthalmic emulsions with the help of failure mode and effect analysis (FMEA), (2) to screen the risky formulation and process variables by the Taguchi design, (3) to optimize systematically an emulsion formula by face-centered central composite design (CCD), (4) to incorporate cyclosporin A (0.05 or 0.1% w/w) into the optimized emulsions and predict the in vitro drug release kinetic via a particle diffusion-controlled mathematical model equation, and (5) to assess the emulsion's toxicity using in vitro hemolysis study. Through the risk priority number (RPN) scores of FMEA, half-normal and Pareto charts of the Taguchi design, 3D-response surface graphs, and overlay plots of CCD, the emulsion formula was systematically optimized. Irrespective of the two different drug loadings into optimized emulsions, the drug entrapment efficiency values ranged from 73.20 ± 0.13 to 74.42 ± 0.15%. The film diffusion or ion-exchange process fails to interpret the in vitro drug release kinetic profile. A permissible percentage hemolysis value of above 10% but below 25% guidance was observed for emulsions with or without cyclosporin A. The systematically optimized phospholipidless ophthalmic emulsions could further be exploited commercially for managing dry-eye syndrome.