Advancements in sunscreen formulations: integrating polyphenolic nanocarriers and nanotechnology for enhanced UV protection.

Sunscreens are essential in protecting the skin from harmful effects of ultraviolet radiation (UVR). These formulations, designed to absorb, block, or scatter UVR, offer vital protection against skin aging, sunburns, and the development of skin cancers like melanomas. However, some sunscreens, especially those containing organic/chemical compounds, can cause allergic reactions. To address this, researchers are extensively investigating formulations that incorporate plant extracts rich in polyphenols, such as flavonoids and carotenoids, which can be considered safer alternatives. Products derived from plants are commonly used in cosmetics to counteract skin aging due to their antioxidant activity that combat harmful free radicals. This review focuses on evaluating the advancements in chemical and natural sunscreens, exploring the integration of polyphenolic nanocarriers within sunscreen formulas, their interaction with UVR, and utilizing nanotechnology to enhance their effectiveness. An attempt has been made to highlight the concerns related to toxicity associated with their use and notable advancements in the regulatory aspects governing their utilization.

Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations.

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.

Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability.

Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of ß1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.

Evolving Era of "Sponges": Nanosponges as a Versatile Nanocarrier for the Effective Skin Delivery of Drugs.

BACKGROUND: Nanosponge, as a carrier for the skin delivery system for drugs, plays a vital role. It not only serves to administer the drug to the targeted layer of skin but also increases the drug retention and deposition on the skin. OBJECTIVE: In this review, we aim to highlight the effects of several processes and formulation variables prompting the characteristics of various nanosponges for the delivery of drugs into/ across the skin. METHODS: In the present review article, the overall introduction of nanosponges, their preparation, characteristic features, advantages, disadvantages, and factors affecting their preparation, are covered. Furthermore, an elaborative description of nanosponges for skin delivery and its toxicological perspective with some referential examples of nanosponge drugs has also been deliberated here. RESULTS: Factors associated with the formation of nanosponges can directly or indirectly affect its efficacy in the skin delivery of drugs. These nanoforms are efficient in delivering the drugs which possess lower aqueous solubility, therefore, the aqueous solubility of drugs possessing a narrow therapeutic window can easily be enhanced. It also helps in achieving targeted drug delivery, controlled release of drugs, increases bioavailability, reduces drug toxicity, decreases drug degradation, and many more. CONCLUSION: Nanosponges have been identified as potential drug delivery carriers into as well as across skin. Delivery of biologics such as vaccines, enzymes, peptides, proteins, and antibodies, is also gaining attention in the recent past.

Full Factorial Design for Development and Validation of a Stability-Indicating RP-HPLC Method for the Estimation of Timolol Maleate in Surfactant-Based Elastic Nano-Vesicular Systems.

A novel isocratic stability-indicating chromatographic method was developed, optimized and validated using Design-Expert® following ICH guidelines for the quantification of Timolol maleate (TM). The intrinsic stability of TM was assessed by force degradation studies, which concluded no extensive degradation except under alkaline and oxidative conditions. TM was quantified accurately in the surfactant-based elastic vesicular system by separating it on Hypersil BDS C8 column using triethylamine in H2O (0.15%v/v; pH 3.0) and acetonitrile (ACN; 65:35%v/v). The influence of variable factors like mobile phase pH, injection volume (µL), flow rate (mL/min) and ACN content (%) on method responses were assessed using a full factorial design. The method was linear between 0.05 and 10 µg/mL with an R2 value of 0.9993. Limit of detection and limit of quantification were found to be 0.90 and 27.2 ng/mL. The method was specific, with recovery in plain drug solution of 89-92% and elastic nanovesicles of 90-93%. The experimental model was significant (P < 0.0001) as indicated by deliberate changes in the method analyzed through analysis of variance. The total drug content in elastic nanovesicles was estimated to be 9.53 ± 0.01 mg/20-mL dispersion and entrapment efficiency was 44.52 ± 0.73%. The developed method was rapid, economic and precise for the quantification of TM in bulk and vesicular system.

Analytical and bioanalytical HPLC method for simultaneous estimation of 5-fluorouracil and sonidegib.

Aim: To develop a new sensitive RP-HPLC method for simultaneous estimation of 5-fluorouracil (5-FU) and sonidegib (SDG). Materials & methods: Analytical and bioanalytical methods for simultaneous quantification of 5-FU and SDG in bulk, nanoformulations and in rat plasma were developed and validated using a gradient elution technique. Results: Separation of the analytes was effected on a Luna® C18 LC column using a mobile mixture comprising acetonitrile and acidified water. 5-FU and SDG were extracted from plasma matrix using liquid-liquid extraction. The applicability of the method was verified through single-dose oral pharmacokinetic study in Wistar rats. Conclusion: The developed methods allow a specific, sensitive and steady analytical procedure for the simultaneous estimation of 5-FU and SDG in nanoformulations and biological matrix.

Metamorphosis of Twin Screw Extruder-Based Granulation Technology: Applications Focusing on Its Impact on Conventional Granulation Technology.

In order to be at pace with the market requirements of solid dosage forms and regulatory standards, a transformation towards systematic processing using continuous manufacturing (CM) and automated model-based control is being thought through for its fundamental advantages over conventional batch manufacturing. CM eliminates the key gaps through the integration of various processes while preserving quality attributes via the use of process analytical technology (PAT). The twin screw extruder (TSE) is one such equipment adopted by the pharmaceutical industry as a substitute for the traditional batch granulation process. Various types of granulation techniques using twin screw extrusion technology have been explored in the article. Furthermore, individual components of a TSE and their conjugation with PAT tools and the advancements and applications in the field of nutraceuticals and nanotechnology have also been discussed. Thus, the future of granulation lies on the shoulders of continuous TSE, where it can be coupled with computational mathematical studies to mitigate its complications.

Exploring potential formulation strategies for chemoprevention of breast cancer: a localized delivery perspective.

This review focuses on the various formulation approaches that have been explored to achieve localized delivery in breast cancer. The rationale behind the necessity of localized drug delivery has been extensively reviewed. The review also emphasizes the various possible routes for achieving localized drug delivery. Particularly, different types of nanoplatforms like lipid-based drug carriers, polymeric particles, hydrogels, drug conjugates and other formulation strategies like microneedles and drug-eluting implants, which have been used to increase tumor retention and subsequently halt tumor progression, have been deliberated here. In addition, the significant challenges that may be encountered in the delivery of anticancer drugs and the aspects that require careful evaluation for effective localized delivery of chemotherapeutic agents have been discussed.

Simultaneous Estimation of Apremilast and Betamethasone Dipropionate in Microsponge-Based Topical Formulation using a Stability Indicating RP-HPLC Method: A Quality-by-Design Approach.

A stability-indicating reverse phase high-performance liquid chromatography method was developed and validated for simultaneous quantification of apremilast (APL) and betamethasone dipropionate (BD) in bulk as well as drug loaded microsponges. Various mobile phase systems were screened to check the system suitability followed by force degradation analysis to determine APL and BD stability under varying stress conditions. A central composite design model was used to optimize the column temperature and flow rate using Design Expert® (9.0.1). One factor at a time approach with five independent factors were used to validate the robustness of the method. Finally, APL and BD were precisely and accurately quantified from drug loaded microsponges using the validated method. A favorable separation of APL and BD was obtained on a Phenomenex® Luna C18 column using a mixture of 50 mM phosphate buffer containing 0.1% triethylamine (pH 6.1) and acetonitrile (60:40%v/v) as mobile phase. Both the drugs were found to be stable when exposed to stressors such as heat-, light-, alkali-, acid- and peroxide-induced degradation. The calibration curves were found to be linear with appreciable limit of detection and limit of quantification. Recovery and percentage relative standard deviation of peak areas for APL and BD were found to be < 2.0% and 99-100% in bulk drug solution and <2.0% and 99-103% in microsponge formulation, respectively. Statistical analysis using analysis of variance indicated that the model was significant (P < 0.001). Hence, the developed method can be effectively used to quantify APL and BD, both in bulk as well as microsponge formulations.

Hot liquid extrusion assisted drug-cyclodextrin complexation: a novel continuous manufacturing method for solubility and bioavailability enhancement of drugs.

In this study, drug-cyclodextrin (CD) complexes were prepared using hot liquid extrusion (HLE) process with an aim to improve solubility and bioavailability of carbamazepine. Saturation solubility studies of CBZ in water and different pH media showed a pH-independent solubility. Phase solubility studies of CBZ at different molar concentrations of beta-cyclodextrin (ß-CD) and hydroxypropyl beta-cyclodextrin (HP-ß-CD) indicated AL-type solubility profile with stability constants of 574 M-1 and 899 M-1 for ß-CD and HP-ß-CD. Drug-ß-CD and drug-HP-ß-CD complexes were prepared using HLE process and conventional methods (such as physical mixture, kneading method, and solvent evaporation) as well. Optimized complexes prepared using HLE viz. CBP-4 and CHP-2 showed a solubility of 4.27 ± 0.09 mg/mL and 6.39 ± 0.09 mg/mL as compared to plain CBZ (0.140 ± 0.007 mg/mL). Formation of drug-CD inclusion complexes was confirmed using DSC, FTIR, and XRD studies. Drug release studies indicated highest release of CBZ from CHP-2 (98.69 ± 2.96%) compared to CBP-4 (82.64 ± 2.45%) and plain drug (13.47 ± 0.54%). Complexes prepared using kneading showed significantly lesser drug release (KMB 75.52 ± 2.68% and KMH 85.59 ± 2.80%) as that of CHP-2 and CBP-4. Pre-clinical pharmacokinetic studies in Wistar rats indicated a significant increase in Cmax, Tmax, AUC, and mean residence time for CHP-2 compared to KMH and plain CBZ. All these results suggest that HLE is an effective method to increase the solubility of poorly water-soluble drugs. Graphical Abstract.

Factors affecting the morphology of some organic and inorganic nanostructures for drug delivery: characterization, modifications, and toxicological perspectives.

Introduction: In this review, we aim to highlight the impact of various processes and formulation variables influencing the characteristics of certain surfactant-based nanoconstructs for drug delivery. Areas covered: The review includes the discussion on processing parameters for the preparation of nanoconstructs, especially those made up of surfactants. Articles published in last 15 years (437) were reviewed, 381 articles were selected for data review and most appropriate articles (215) were included in article. Effect of variables such as surfactant concentration and type, membrane additives, temperature, and pH-dependent transitions on morphology has been highlighted along with effect of shape on nanoparticle uptake by cells. Various characterization techniques explored for these nanostructures with respect to size, morphology, lamellarity, distribution, etc., and a separate section on polymeric vesicles and the influence of block copolymers, type of block copolymer, control of block length, interaction of multiple block copolymers on the structure of polymersomes and chimeric nanostructures have been discussed. Finally, applications, modification, degradation, and toxicological aspects of these drug delivery systems have been highlighted. Expert opinion: Parameters influencing the morphology of micelles and vesicles can directly or indirectly affect the efficacy of small molecule cellular internalization as well as uptake in the case of biologicals.[Figure: see text].

Naringin nano-ethosomal novel sunscreen creams: Development and performance evaluation.

Long term exposure of skin to UV rays produces detrimental effects such as premature skin-ageing and skin cancer. Although, zinc oxide (ZnO) and titanium dioxide (TiO2) are good sunscreen agents, they do not provide highly efficient UV radiation protection and antioxidant and anti-aging effects. The present study was aimed at developing and characterizing ethosomes loaded with naringin and then to incorporate them into sunscreen creams containing nano-ZnO and -TiO2 to achieve adequate skin penetration and skin retention so as to scavenge the free radicals by virtue of naringin's antioxidant property. Ethosomes were prepared and optimized with respect to concentrations of ethanol and cholesterol, time of sonication, drug and lipid ratio and amount of drug. The ethosomes were evaluated for size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency and surface morphology. Ethosomal sunscreen creams were evaluated for physicochemical tests, spreadability, antioxidant, cytotoxicity and skin permeation studies. Optimized ethosomal formulation exhibited average vesicle size, PDI, ZP and drug encapsulation efficiency of 142.5 ± 5.6 nm, 0.199 ± 0.007, -72.5 ± 2.9 mV and 33.79 ± 1.35%, respectively. Naringin ethosomes showed enhanced retention in the skin (403.44 ± 15.33 µg/cm2) compared to naringin suspension (202.81 ± 9.45 µg/cm2). The optimized sunscreen cream exhibited SPF of 21.21 ± 0.62 with negligible permeation of naringin across the skin. Ethosomes showed pronounced skin permeation for naringin and optimized cream containing naringin ethosomes along with nano- ZnO and TiO2 showed good skin retention for naringin.

Sunscreen creams containing naringenin nanoparticles: Formulation development and in vitro and in vivo evaluations.

BACKGROUND: The aim of this study was to develop sunscreen creams containing polymeric nanoparticles (NPs) of naringenin for photoprotective and antioxidant effects. METHODS: Polymeric NPs of naringenin were prepared and optimized. The NPs were incorporated into sunscreen creams and evaluated for in vitro and in vivo skin retention. RESULTS: The optimized naringenin NPs showed a size of 131.2 nm, zeta potential -25.4 mV, and entrapment efficiency 32.45%. The absence of drug-excipient interaction was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimetry. X-Ray diffraction analysis demonstrated the amorphization of naringenin in nanoparticles. Transmission electron microscopy showed the sphericity of the NPs with the size of <200 nm. Cytotoxicity assessment in HaCaT cells indicated non-toxic nature of naringenin NPs. In vitro skin permeation studies demonstrated that higher amount of naringenin permeated at the end of 12 hours (Q12 hours  = 184.03 ± 3.37 µg/cm2 ) and deposited in the skin (10.38 ± 0.48 µg/cm2 ) from NPs as compared to plain naringenin. Sunscreen creams (SC1-SC5) containing plain naringenin or NPs with/without nano-zinc oxide and nano-titanium dioxide were prepared and evaluated. Optimized cream (SC5) containing naringenin NPs showed highest SPF value and enhanced skin retention of naringenin in comparison with NPs in suspension form and other cream formulations. CONCLUSION: Optimized nanoparticulate sunscreen cream exhibited highest skin retention and negligible skin permeation of naringenin besides showing excellent SPF value.

Liposome-encapsulated diacyl glycerol and inositol triphosphate-induced delayed oocyte activation and poor development of parthenotes.

OBJECTIVE: To explore the ability of diacyl glycerol (DAG) and inositol triphosphate (IP3), two major secondary messengers in the calcium signaling pathway, in activating oocytes. MATERIAL AND METHODS: Oocyte cumulus complex obtained from superovulated Swiss albino mice were incubated in M16 medium with liposome-encapsulated 1,2-Dipalmitoyl-sn-glycerol (LEDAG) and/or IP3 for 3 h. Strontium chloride was used as positive control. The activation potential, ploidy status, and blastocyst rate was calculated. RESULTS: Both DAG and IP3, individually, induced activation in ~98% of oocytes, which was significantly higher (p<0.01) than activation induced by strontium chloride (60%). Delayed pronucleus formation and a higher percentage of diploid parthenotes was observed in oocytes activated with LEDAG and/or IP3. However, these embryos failed to progress beyond the 6-8-cell stage. Only when the medium was supplemented with LEDAG (5 µg/mL) and IP3 (10 µg/mL) could activated oocytes progress till the blastocyst stage (5.26%), which was lower than the blastocyst rate in the positive controls (13.91%). CONCLUSION: The results of the present study indicate that DAG and IP3 can induce delayed oocyte activation and poor development of parthenotes in vitro.

Indian propolis ameliorates the mitomycin C-induced testicular toxicity by reducing DNA damage and elevating the antioxidant activity.

Development of excellent curative therapy for most of the malignancies has resulted in a growing population of cancer survivors who are at increased risk for a variety of health problems including infertility. Therefore, fertility preservation has become an important issue during cancer treatment in recent years. Combination therapy with natural agents such as vitamins, antioxidants, dietary supplements, and plant products are considered as an attractive option to mitigate normal tissue toxicity imparted by chemotherapy. The aim of the present study was to explore the beneficial effect of hydroethanolic extract of Indian propolis (HEIP) on mitigating mitomycin C (MMC)-induced testicular damage and its mechanism of action. Healthy adult male mice were injected intraperitoneally with saline, MMC, HEIP and HEIP followed by MMC after 1h. The animals were dissected at 35days after various treatments to analyze testicular function. MMC administration resulted in significant reduction in testicular function in a dose-dependent manner at 35days after treatment which significantly improved by HEIP pre-treatment. At 24h after treatment, MMC induced significant increase in oxidative stress, γ-H2AX foci and expression of RAD51 and KU80 in testicular cells. Prior treatment with HEIP decreased the oxidative stress, reduced DNA damage and restored the testicular testosterone and inhibin B level. In conclusion, co-administration of Indian propolis extract may play a promising beneficial role in fertility preservation of males undergoing chemotherapy.

Peptide dendrimer-conjugates of ketoprofen: Synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery.

The aim of this study was to evaluate skin delivery of ketoprofen when covalently tethered to mildly cationic (2+ or 4+) peptide dendrimers prepared wholly by solid phase peptide synthesis. The amino acids glycine, arginine and lysine formed the dendrimer with ketoprofen tethered either to the lysine side-arm (Nε) or periphery of dendrimeric branches. Passive diffusion, sonophoresis- and iontophoresis-assisted permeation of each peptide dendrimer-drug conjugate (D1-D4) was studied across mouse skin, both in vitro and in vivo. In addition, skin toxicity of dendrimeric conjugates when trialed with iontophoresis or sonophoresis was also evaluated. All dendrimeric conjugates improved aqueous solubility at least 5-fold, compared to ketoprofen alone, while also exhibiting appreciable lipophilicity. In vitro passive diffusion studies revealed that ketoprofen in its native form was delivered to a greater extent, compared with a dendrimer-conjugated form at the end of 24h (Q24h (µg/cm2): ketoprofen (68.06±3.62)>D2 (49.62±2.92)>D4 (19.20±0.89)>D1 (6.45±0.40)>D3 (2.21±0.19). However, sonophoresis substantially increased the skin permeation of ketoprofen-dendrimer conjugates in 30min (Q30min (µg/cm2): D4 (122.19±7.14)>D2 (66.74±3.86)>D1 (52.10±3.22)>D3 (41.66±3.22)) although ketoprofen alone again proved superior (Q30min: 167.99±9.11µg/cm2). Next, application of iontophoresis was trialed and shown to considerably increase permeation of dendrimeric ketoprofen in 6h (Q6h (µg/cm2): D2 (711.49±39.14)>D4 (341.23±16.43)>D3 (89.50±4.99)>D1 (50.91±2.98), with a Q6h value of 96.60±5.12µg/cm2 for ketoprofen alone). In vivo studies indicated that therapeutically relevant concentrations of ketoprofen could be delivered transdermally when iontophoresis was paired with D2 (985.49±43.25ng/mL). Further, histopathological analysis showed that the dendrimeric approach was a safe mode as ketoprofen alone. The present study successfully demonstrates that peptide dendrimer conjugates of ketoprofen, when combined with non-invasive modalities, such as iontophoresis can enhance skin permeation with clinically relevant concentrations achieved transdermally.

Influence of peptide dendrimers and sonophoresis on the transdermal delivery of ketoprofen.

The aim of this study was to determine the individual and combined effects of peptide dendrimers and low frequency ultrasound on the transdermal permeation of ketoprofen. Arginine terminated peptide dendrimers of varying charges (4+, 8+ and 16+, named as A4. A8 and A16 respectively) were synthesized and characterized. Ketoprofen was subjected to passive, peptide dendrimer-assisted and sonophoretic permeation studies (with and without dendrimer application) across Swiss albino mouse skin, both in vitro and in vivo. The studies revealed that the synthesized peptide dendrimers considerably increased the transdermal permeation of ketoprofen and displayed enhancement ratios of up to 3.25 (with A16 dendrimer), compared to passive diffusion of drug alone in vitro. Moreover, the combination of peptide dendrimer treatment and ultrasound application worked in synergy and gave enhancement ratios of up to 1369.15 (with ketoprofen-A16 dendrimer complex). In vivo studies demonstrated that dendrimer and ultrasound-assisted permeation of drug achieved much higher plasma concentration of drug, compared to passive diffusion. Comparison of transdermal and oral absorption studies revealed that transdermal administration of ketoprofen with A8 dendrimer showed comparable absorption and plasma drug levels with oral route. The excised mouse skin after in vivo permeation study with dendrimers and ultrasound did not show major toxic reactions. This study demonstrates that arginine terminated peptide dendrimers combined with sonophoresis can effectively improve the transdermal permeation of ketoprofen.

Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q12), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.

CONTEXT: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. OBJECTIVE: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. MATERIALS AND METHODS: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. RESULTS AND DISCUSSION: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 µg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. CONCLUSION: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.