Drug Delivery Formulations Research Articles

α-Cyclodextrin-based poly(pseudo)rotaxane for antifungal drug delivery to the vaginal mucosa

This work aimed to evaluate poly(pseudo)rotaxanes (PPRs) potential for vaginal antifungal delivery. For this, PPRs containing terbinafine (TB) 2 % were obtained using two small surfactants, Kolliphor® RH40 and Gelucire® 48/16, and different α-cyclodextrin (α-CD) concentrations (5 and 10 %). PPRs were characterized by their physicochemical characteristics, irritation, and mucoadhesion capabilities. Formulations' performance was assessed in a vertical penetration model, which uses ex vivo entire porcine vagina. Conventional penetration experiments with excised vaginal tissue were performed as a control. Results showed all formulations were non-irritant according to the HET-CAM test. Furthermore, PPRs with 10 % αCD showed superior mucoadhesion (p < 0.05). Conventional horizontal penetration studies could not differentiate formulations (p > 0.05). However, PPRs with 10 % αCD presented a better performance in vertical ex vivo studies, achieving higher drug penetration into the vaginal mucosa (p < 0.05), which is probably related to the formulation's prolonged residence time. In addition, the antifungal activity of the formulations was maintained against Candida albicans and C. glabrata cultures. More importantly, the formulation's viscosity and drug delivery control had no negative impact on the antifungal activity. In conclusion, the best performance in a more realistic model evidenced the remarkable potential of PPRs for vaginal drug delivery.

A comprehensive review on the COVID-19 vaccine and drug delivery applications of interpenetrating polymer networks.

An interpenetrating polymer network (IPNs) is a concoction of two or more polymers (natural, synthetic, and/or a combination of both) in which at least one polymer is synthesized or crosslinked in the intimate presence of the other. These three-dimensional networked systems have gained prominence in a series of biomedical applications, especially in the last two decades. The last decades witnessed a surge in the meaningful applications of interpenetrating polymer networks, especially in drug delivery as simple IPN systems advanced and resulted in the formation of highly efficient microspheres, nanoparticles, nanogels, and hydrogels, intelligent enough to sense and respond to changes in external stimuli such as temperature, pH, and ionic strength. The structure of the polymers, crosslinking agents, crosslinking density, and polymerization method play an integral role in determining the properties and application of IPNs in drug delivery. This review article is a modest effort to highlight the importance and applications of different types of interpenetrating polymer networks for the sustained, site-specific drug delivery of various therapeutic formulations, as witnessed in scientific research literature over the past 22 years (2000-2022). A special section of the manuscript is devoted to studying the efficacy of network polymers in vaccine delivery and highlighting the future scope (if any) of incorporating the IPN system in COVID-related vaccine/drug delivery. Four key focus areas in this review article [1, 2].

Artificial Intelligence: Comprehensive Overview and its Pharma Application

Artificial Intelligence (AI) focuses in producing intelligent modeling, which helps in imagining knowledge, cracking problems and decision making. In the year 1943, the first work which is now recognized as AI was done by Warren McCulloch and Walter pits. Previously, Artificial Intelligence was only limited to the field of engineering, but recently, AI plays an important role in various fields of pharmacy like drug discovery, drug delivery formulation development, marketing, management, marketing, quality assurance, hospital pharmacy etc. In drug discovery and drug delivery formulation development, various Artificial Neural Networks (ANNs) like Deep Neural Networks (DNNs) or Recurrent Neural Networks (RNNs) are being employed. Several implementations of drug discovery have currently been analyzed and supported the power of the technology in quantitative structure-property relationship (QSPR) or quantitative structure-activity relationship (QSAR). In addition, de novo design promotes the invention of significantly newer drug molecules with regard to desired/optimal qualities. Now the robots are using in the various medical procedures as they are more trustworthy for doctors, as they are more advanced in their work, as they can do any task within the short time period and effectively than humans. This is concluded that AI is the new evolving field in every sector, even in pharmacy, and it need more development for updating the current scenario as well as for new researches.

Development and Preliminary Characterization of Polyester-Urethane Microparticles Used in Curcumin Drug Delivery System for Oropharyngeal Cancer.

Background and Objectives: Curcumin (Cc) as an active substance is known for its anti-inflammatory, anticoagulant, antioxidant, and anti-carcinogenic effects, together with its role in cholesterol regulation, and its use in different gastrointestinal derangements. On the other hand, curcumin can be used for its properties as an inactive substance, with Cc particles being more often tested in pharmaceutical formulations for drug delivery, with promising safety records and kinetics. The aim of this research was to obtain and characterize polyurethane microparticles that can be used as a carrier with a controlled Cc release. Materials and Methods: The in vitro samples were characterized by the Zetasizer procedure, and UV-Vis spectroscopy, while the in-vivo measurements on human subjects were performed by non-invasive skin assays (trans-epidermal water loss, erythema, and skin hydration). A total of 16 patients with oropharyngeal cancer stages II and III in equal proportions were recruited for participation. Results: The experimental values of sample characteristics using the Zetasizer identified a mean structural size of 215 nm in the polyester-urethane preparate (PU), compared to 271 nm in the curcumin-based PU. Although the size was statistically significantly different, the IPDI and Zeta potential did not differ significantly (22.91 mV vs. 23.74 mV). The average age during the study period was 57.6 years for patients in the PU group, respectively, and 55.1 years in those who received the curcumin preparations. The majority of oropharyngeal cancers were of HPV-related etiology. There were no significant side effects; 75.0% of patients in the PU group reporting no side effects, compared to 87.5% in the Cc group. The 48 h TEWL measurement at the end of the experiment found a statistically significant difference between the PU and the Cc group (2.2 g/h/m2 vs. 2.6 g/h/m2). The erythema assessment showed a starting measurement point for both research groups with a 5.1-unit difference. After 48 h, the difference between PU and PU_Cc was just 1.7 units (p-value = 0.576). The overall difference compared to the reference group with sodium lauryl sulfate (SLS) was statistically significant at a 95% significance level. Conclusions: Our findings indicate the obtaining of almost homogeneous particles with a medium tendency to form agglomerations, with a good capacity of encapsulation (around 60%), a medium release rate, and a non-irritative potential. Therefore, this polyester-urethane with Cc microparticles can be tested in other clinical evaluations.

Development of a Eudragit-Chitosan Nanosystem for the pH-Dependent Transport of Duloxetine to the Brain: Synthesis, Characterization and In Silico Modeling Analysis

The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) nanoparticles enclosed in an oral gelatin capsule and to evaluate the potential to transport DLX to the blood-brain barrier (BBB)for improved neuro-availability. The utilization of Eudragit® with chitosan offers a pH-dependent controlled drug release. The physicochemical properties of the formulated DLX-loaded Eud-CHT nanosystem were confirmed using various characterization techniques. SEM confirmed the nanoparticle morphology and pore size distribution. The particle size was 100 ± 73,41 nm, with a polydispersity index (PDI) of 0,283 and zeta potential of 16±2,79 mV. Drug entrapment efficacy (DEE) of 72% was attained, and molecular modelling predicted an efficient and controllable drug delivery system. The release of DLX from the nanosystem was evaluated at pH1.2, pH 6.8 and pH 7.4. At a pH of 6.8, 40 % of DLX was released, with only 20 % at pH 1.2 and 35% at pH 7.4. This demonstrated DLX's pH-dependent release and the Eud-CHT nanosystem's shielding effect at gastric pH. In addition, HEK 293 neural cells confirmed the non-toxicity of the DLX-Eud-CHT nanosystem. In silico modelling revealed a DLX-Eud-CHT composite with an outer cationic surface attributable to the EUD moieties on nanoparticles for preferential cell recognition and uptake at the anionic cell interface. The combined trials and results from the synthesis of DLX-Eud-CHT nanoparticles showed that these nanoparticles could be utilized as a potentially invaluable formulation for oral drug delivery of duloxetine with improved neuro-availability.

Recent Developments and Anticancer Therapeutics of Paclitaxel: An Update.

Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources - like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.

Development, Validation and Application of a Novel UHPLC-UV Method for the Simultaneous Determination of Valsartan and Nifedipine in the New Formulation of Self-Nanoemulsifying Drug Delivery Systems

Our objective is to develop a robust method to quantify valsartan (VAL) and nifedipine (NIF) in developed a self-nanoemulsifying drug delivery formulation. An in-house ultra-high-performance liquid chromatography (UHPLC UV) method has been developed and validated for the simultaneous determination of VAL and NIF. The UV detection was performed isocratically, with a mobile phase comprised of acetonitrile, methanol and ammonium formate in the ratios of (15:45:40% v/v) and a flow rate of 0.35 mL/min at 236 nm. The correlation coefficients (R2) of this linear regression were 0.9984 for NIF and 0.9997 for VAL, respectively. The limit of detection (LOD) for NIF as 3.78 ppm, whereas the limit of detection (LOD) for VAL was 1.56 ppm. The limit of quantification (LOQ) of NIF and VAL were 11.47 ppm and 4.73 ppm, respectively. This method was effectively utilized to determine the amount of drug entrapped and drug loading efficiency percentage of the NIF and VAL self-nanoemulsifying formulations.

Integration of transdermal chemistry and network pharmacology to decipher the mechanism of ShexiangZhuifeng analgesic plaster to treat rheumatoid arthritis

BackgroundTransdermal patches are an effective form of treatment for rheumatoid arthritis (RA), and they have a number of benefits, including patient compliance, accessibility, and low systemic toxicity. ShexiangZhuifeng Analgesic Plaster (SZAP), a patch made up of many traditional medicines, has been successfully utilized in numerous clinical trials to treat RA. However, information about anti-RA processes and transdermal active components is still emerging. PurposeOur objectives were to identify the transdermal active components of SZAP and investigate its anti-RA mechanisms, primarily focused on joint inflammation. MethodsThe collagen-induced arthritis (CIA) rats were created first, and then the arthritis score, Paw thickness, and morphology feature of joint synovial were assessed after 7 days of therapy with SZAP. Moreover, the Franz diffusion cell and UPLC-MS technologies were combined to identify and measure the transdermal active ingredients of SZAP. Furthermore, network pharmacology was utilized to anticipate the putative the mechanism of SZAP for treating RA. Finally, the results of network pharmacology were validated using LPS-induced RAW 264.7 cells and CIA rats. ResultsSZAP significantly reduced paw thickness, arthritic score and pathological characteristics of joint synovitis in (CIA) rats. Additionally, 12 transdermal active components of SZAP were identified, and network pharmacology prediction results suggested that SZAP may alleviate joint synovial inflammation by blocking the Akt/mTOR/HIF-1 pathway. Our investigations' findings demonstrated that SZAP dramatically reduced the concentrations of excess cytokines (IL6, VEGF, and TNF-α), as well as the protein overexpression of the AKT/mTOR/HIF- pathway (HIF-1, p-AKT, and p-mTOR), whereas its anti-inflammation effect was reversed once AKT or mTOR was activated. ConclusionBy blocking the AKT/mTOR/HIF-1 pathway, SZAP can lessen the release of inflammatory mediators, which reduces joint synovial inflammation associated with RA. The pharmacological evaluation of TCM transdermal drug delivery formulations like SZAP may be amenable to the integration of transdermal chemistry and network pharmacology approaches.

Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective

The rectal route is an effective route for the local and systemic delivery of active pharmaceutical ingredients. The environment of the rectum is relatively constant with low enzymatic activity and is favorable for drugs having poor oral absorption, extensive first-pass metabolism, gastric irritation, stability issues in the gastric environment, localized activity, and for drugs that cannot be administered by other routes. The present review addresses the rectal physiology, rectal diseases, and pharmaceutical factors influencing rectal delivery of drugs and discusses different rectal drug delivery systems including suppositories, suspensions, microspheres, nanoparticles, liposomes, tablets, and hydrogels. Clinical trials on various rectal drug delivery systems are presented in tabular form. Applications of different novel drug delivery carriers viz. nanoparticles, liposomes, solid lipid nanoparticles, microspheres, transferosomes, nano-niosomes, and nanomicelles have been discussed and demonstrated for their potential use in rectal administration. Various opportunities and challenges for rectal delivery including recent advancements and patented formulations for rectal drug delivery have also been included.

Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment.

Liposomes are well-known nanoparticles with a non-toxic nature and the ability to incorporate both hydrophilic and hydrophobic drugs simultaneously. As modern drug delivery formulations are produced by emerging technologies, numerous advantages of liposomal drug delivery systems over conventional liposomes or free drug treatment of cancer have been reported. Recently, liposome nanocarriers have exhibited high drug loading capacity, drug protection, improved bioavailability, enhanced intercellular delivery, and better therapeutic effect because of resounding success in targeting delivery. The site targeting of smart responsive liposomes, achieved through changes in their physicochemical and morphological properties, allows for the controlled release of active compounds under certain endogenous or exogenous stimuli. In that way, the multifunctional and stimuli-responsive nanocarriers for the drug delivery of cancer therapeutics enhance the efficacy of treatment prevention and fighting over metastases, while limiting the systemic side effects on healthy tissues and organs. Since liposomes constitute promising nanocarriers for site-targeted and controlled anticancer drug release, this review focuses on the recent progress of smart liposome achievements for anticancer drug delivery applications.

Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation.

Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections.

Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

Buccal drug delivery system

The buccal area of the oral mucosa provides an adorable channel of systemic medication distribution within the mouth mucosa. Drugs are delivered via oral mucosal layer, that has a higher first-pass metabolism and degrades gastrointestinal. The medication is immediately transmitted via the systemic circulation via the buccal drug delivery mechanism, which allows for painless administration, quick enzymatic action, high bioavailability, and reduced liver metabolism. The disadvantages of the oral drug delivery route include substantial presystemic metabolism, which causes medicines to a break down in an acidic environment due to poor absorption. Buccal delivery is an attractive administrative route due to its ease of delivery through the buccal mucosal membrane lining of the oral cavity. This review paper provides a comprehensive overview of the oral mucosa, mucoadhesion, variables influencing the whole process, assessment methodologies, and how to eliminate obstacles when formulating buccal drug delivery formulations.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

Glutaraldehyde crosslinked doxorubicin promotes drug delivery efficiency using cobalt ferrite nanoparticles

Doxorubicin (DOX) is a common chemotherapy agent that is used in clinics for the treatment of a wide spectrum of cancers. Herein, a novel approach for improving doxorubicin loading on nanoparticles and also controlled release is suggested using crosslinking doxorubicin molecules with glutaraldehyde. We investigated the loading efficiency of doxorubicin on CoFe2O4 nanoparticles in the absence and presence of glutaraldehyde. Based on the feasible, one-pot, and time-saving approach suggested here, the crosslinked DOX showed loading efficiency about twice more in comparison with the non-crosslinked DOX. In vitro doxorubicin release of three formulations including DOX crosslinked with glutaraldehyde (DOXGA), DOX loaded on CoFe2O4 (CFDOX) and DOX loaded on CoFe2O4 using glutaraldehyde (CFDOXGA) yielded a sustained release. The kinetic models such as first-order, Sahlin-Peppas, and Higuchi were employed for further exploration of DOX release profile. Our suggested method might extend to other nanomaterial-based drug delivery formulations to promote drug delivery efficiency.

Solid-to-Liposome Conformational Transition of Phosphatidylcholine and Phosphatidylserine Probed by Atomic Force Microscopy, Infrared Spectroscopy, and Density Functional Theory Calculations.

Liposomes are emerging therapeutic formulations for site-specific delivery of chemotherapeutic drugs. The efficiency and selectivity of drug delivery by these carriers largely rely on their surface properties, shape, and size. There is a growing demand for analytical approaches that can be used for structural and morphological characterization of liposomes at the single-vesicle level. AFM-IR is a modern optical nanoscopic technique that combines the advantages of scanning probe microscopy and infrared spectroscopy. Our findings show that AFM-IR can be used to probe conformational changes in phospholipids that take place upon their assembly into liposomes. Such conclusions can be made based on the corresponding changes in intensities of the lipid vibrational bands as the molecules transition from a solid state into large unilamellar vesicles (LUVs). This spectroscopic analysis of LUV formation together with density functional theory calculations also reveals the extent to which the molecular conformation and local environment of the functional groups alter the AFM-IR spectra of phospholipids. Using melittin as a test protein, we also examined the extent to which LUVs can be used for protein internalization. We found that melittin enters LUVs nearly instantaneously, which protects it from possible structural modifications that are caused by a changing environment. This foundational work empowers AFM-IR analysis of liposomes and opens new avenues for determination of the molecular mechanisms of liposome-drug interactions.

Development and evaluation of ultradeformable vesicles loaded transdermal film of boswellic acid

BackgroundBoswellic acid (BA), a phytoconstituent obtained from Boswellia serrata, suffers from several limitations after oral administration such as poor systemic absorption, high first-pass metabolism and high frequency of dose requirement, which creates a need to develop an alternative route for drug administration via novel drug delivery formulation. The present research work aims at developing ultradeformable vesicular carriers (transferosomes) for transdermal delivery of boswellic acid to effectively deliver the drug into deeper layers of the skin reaching the target site and thus improving its systemic bioavailability. Ultradeformable vesicles were prepared by thin-film hydration technique, and the formulation was optimized using 32 full factorial design where the amount of lecithin (mg) and concentration of surfactant (%) were considered as independent variables. The formulated boswellic acid-loaded vesicles were incorporated into transdermal film via solvent evaporation technique using the blend of polymers such as starch and HPMC K4M.ResultsThe BA-loaded transferosomes were optimized based on vesicle size (nm) and drug entrapment efficiency (%EE), and the results were found to be 205.4 ± 1.215 nm and 86.39 ± 0.019%, respectively. Transmission electron microscopy (TEM) of optimized batch showed spherical shape of vesicles with identified lamellarity, surface charge of vesicles with high negative value − 15.2 mV that suggests electrostatic repulsion between vesicles, while the formulation showed good deformability index of 11.31 ± 0.032% due to use of Tween 80 as surfactant. In vitro permeation study demonstrated sustained release pattern of 96.53 ± 0.023% up to 24 h. Also, the in vitro drug diffusion study was carried out for transfersomal transdermal film which exhibited enhanced permeation and sustained retention of drug up to 94.71 ± 0.019% for 24 h.ConclusionAccordingly, the research work suggested that the transferosomes provided an efficient nanosized carriers for enhanced permeation of boswellic acid into deeper layers of skin and could successfully exhibit its therapeutic effect.

Interpenetrating polymeric network (IPNs) in ophthalmic drug delivery: Breaking the barriers.

To maintain the therapeutic drug concentration for a prolonged period of time in aqueous and vitreous humor is primary challenge for ophthalmic drug delivery. Majority of the locally administered drug into the eye is lost as to natural reflexes like blinking and lacrimation resulting in the short span of drug residence. Consequently, less than 5% of the applied drug penetrate through the cornea and reaches the intraocular tissues. The major targets for optimal ophthalmic drug delivery are increasing drug residence time in cul-de-sac of the eye, prolonging intraocular exposure, modulating drug release from the delivery system, and minimizing pre-corneal drug loss. Development of in situ gel, contact lens, intraocular lens, inserts, artificial cornea, scaffold, etc., for ophthalmic drug delivery are few approaches to achieve these major targeted objectives for delivering the drug optimally. Interpenetrating polymeric network (IPN) or smart hydrogels or stimuli sensitive hydrogels are the class of polymers that can help to achieve the targets in ophthalmic drug delivery due to their versatility, biocompatibility and biodegradability. These novel ''smart" materials can alter their molecular configuration and result in volume phase transition in response to environmental stimuli, such as temperature, pH, ionic strength, electric and magnetic field. Hydrogel and tissue interaction, mechanical/tensile properties, pore size and surface chemistry of IPNs can also be modulated for tuning the drug release kinetics. Stimuli sensitive IPNs has been widely exploited to prepare in situ gelling formulations for ophthalmic drug delivery. Low refractive index hydrogel biomaterials with high water content, soft tissue-like physical properties, wettability, oxygen, glucose permeability and desired biocompatibility makes IPNs versatile candidate for contact lenses and corneal implants. This review article focuses on the exploration of these smart polymeric networks/IPNs for therapeutically improved ophthalmic drug delivery that has unfastened novel arenas in ophthalmic drug delivery.

PH-Responsive PEGylated Niosomal Nanoparticles as an Active-Targeting Cyclophosphamide Delivery System for Gastric Cancer Therapy.

A PEGylated niosomal formulation of cyclophosphamide (Nio-Cyclo-PEG) was prepared using a central composite design and characterized in terms of drug loading, size distribution, and average size. The stability of formulations was also studied at different conditions. In vitro cytotoxicity of drug delivery formulations was assessed on gastric cancer cells using MTT assay. The mechanism of cytotoxicity was studied at the transcriptional level by real-time PCR on Caspase3, Caspase9, CyclinD, CyclinE, MMP-2, and MMP-9 genes, while apoptosis was investigated with flow cytometry. The anti-metastatic property was evaluated using the scratch method. Propidium iodide staining was used to study the cell cycle. The results indicated that the as-designed nanocarrier exhibited a controlled drug release pattern with improved nanoparticle stability. It was found that the living cancer cells treated with Nio-Cyclo-PEG showed a significant decrease in number when compared with the niosomal carrier without PEG (Nio-Cyclo) and free drug (Cyclo). Moreover, the drug-loaded nanocarrier induced planned death (apoptosis) in the cancer cells through the regulation of Caspase3, Caspase9, CyclinD, CyclinE, MMP-9, and MMP-2 gene expression, indicating that the Nio-Cyclo-PEG formulation could significantly inhibit the cell cycle at the sub G1 phase as well as prevent the migration of cancer cells. In conclusion, Nio-Cyclo-PEG as developed in this study could serve as an active-targeting drug delivery nanocarriers for gastric cancer therapy with high efficacy and minimal side effects on healthy tissues/cells.

State-of-the-Art and Opportunities for Bioactive Pentacyclic Triterpenes from Native Mexican Plants.

Native Mexican plants are a wide source of bioactive compounds such as pentacyclic triterpenes. Pentacyclic triterpenes biosynthesized through the mevalonate (MVA) and the 2-C-methyl-D-erythritol-phosphate (MEP) metabolic pathways are highlighted by their diverse biological activity. Compounds belonging to the oleanane, ursane, and lupane groups have been identified in about 33 Mexican plants, located geographically in the southwest of Mexico. The works addressing these findings have reported 45 compounds that mainly show antimicrobial activity, followed by anti-inflammatory, cytotoxic, anxiolytic, hypoglycemic, and growth-stimulating or allelopathic activities. Extraction by maceration and Soxhlet with organic solvents and consecutive chromatography of silica gel have been used for their whole or partial purification. Nanoparticles and nanoemulsions are the vehicles used in Mexican formulations for drug delivery of the pentacyclic triterpenes until now. Sustainable extraction, formulation, regulation, isolation, characterization, and bioassay facilities are areas of opportunity in pentacyclic triterpenes research in Mexico while the presence of plant and human resources and traditional knowledge are strengths. The present review discusses the generalities of the pentacyclic triterpene (definition, biogenic classification, and biosynthesis), a summary of the last two decades of research on the compounds identified and their evaluated bioactivity, the generalities about the extraction and purification methods used, drug delivery aspects, and a critical analysis of the advantages and limitations of research carried out in this way.