The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1-37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98-21.3 μm), and zeta potential (- 9.81 to - 21.53 mV). The in vitro drug release (T) was extended to more than three half-lives (2-4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R = 0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membranecamouflaged NPs.

The aim of the current study was to fabricate naturally derived polymer based hydrogels for controlled release of diclofenac sodium (DS) for a long duration of time. In this research work, sodium alginate-co-poly(2-acrylamido-2-methyl propane sulphonic acid) (SA-co-poly(AMPS)) hydrogels were prepared by the free radical polymerization technique, where sodium alginate (SA) and 2-acrylamido-2-methyl propane sulphonic acid (AMPS) were used as the polymer and monomer while ammonium peroxodisulfate (APS) and N,N′-Methylene bisacrylamide (MBA) were used as the initiator and cross-linker, respectively. A swelling study was performed to determine the swelling index of developed hydrogels in both acidic (pH 1.2) and basic (pH 7.4) media and pH-independent swelling was observed due to the presence of AMPS. An in vitro release study was conducted to evaluate the percentage of drug released, and a high release of the drug was found at the higher pH of 7.4. Sol–gel analysis was performed to analyze the crosslinked and uncrosslinked part of the hydrogels, and results showed a rise in gel fraction as the composition of SA, AMPS and MBA increased while the sol fraction decreased and vice versa. This work demonstrated a potential for sustained delivery of diclofenac sodium by employing various concentration of SA, AMPS and MBA.

Background Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3. Methods Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan. Results Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 vs 3.8%, P = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35–8.46, P = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49–109.6, P = <0.001). Skin rash (51 vs 44%) and oral ulcers (45 vs 40%) were high in patients receiving SOF-DCV then SOF-VEL. Conclusions Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.