Radiation-induced skin injury is a common, dose-limiting toxicity of cancer radiotherapy caused by excessive reactive oxygen species (ROS), inflammation, and impaired epidermal repair. Current topical treatments mainly offer symptomatic relief and do not effectively address intracellular oxidative stress. This study reports a hyaluronic acid–functionalized, hesperidin-loaded solid lipid nanoparticle (HSP-HA-SLN) system designed to enhance dermal delivery, skin retention, and intracellular antioxidant activity. HSP-HA-SLNs were prepared by solvent injection and optimized using a Central Composite Design to achieve sub-300 nm particle size and high entrapment efficiency, followed by hyaluronic acid surface functionalization. The optimized formulation was characterized by dynamic light scattering, electron microscopy, thermal, and crystallographic analyses. In vitro drug release, cytocompatibility, intracellular antioxidant activity, and ex vivo skin permeation and retention were evaluated. The nanoparticles exhibited sustained diffusion-controlled drug release, high cytocompatibility, and significantly improved intracellular ROS scavenging compared to free hesperidin. The observed intracellular ROS reduction supports the potential of this system in radiation-induced oxidative stress conditions. Ex vivo studies showed enhanced dermal deposition with minimal surface residue, indicating localized drug reservoir formation. Overall, the HSP-HA-SLN platform overcomes key solubility, permeability, and retention limitations of hesperidin and represents a promising topical nanotherapeutic approach for potential application in radiation-induced skin injury.

The incidence of central nervous system (CNS) disorders is rising globally, particularly as the prevalence of neurodegenerative diseases increases. The primary challenge in such cases is limited transport of therapeutics through the blood-brain barrier (BBB). Statins, widely used for hypercholesterolemia, exhibit pleiotropic neuroprotective effects; however, their therapeutic potential in CNS disorders is restricted by poor brain bioavailability with conventional routes. Intranasal (IN) delivery has long been recognized as a plausible pathway for brain targeting. This narrative review critically examines preclinical literature on IN nanocarrier-based delivery systems developed specifically for statins, with emphasis on nose-to-brain transport, formulation strategies, pharmacokinetics (PK), and neuroprotective outcomes. This work uniquely integrates a formulation-centric comparison of IN nanocarriers for statins. It highlights the potential of IN delivery, discussing the influence of carrier type, physicochemical properties, and delivery strategy on brain targeting efficiency and therapeutic relevance across different neurological indications. IN nanocarrier systems display potential to enhance statin brain delivery by bypassing the BBB and first-pass metabolism. Nevertheless, current evidence is predominantly preclinical, with significant variability in study design, pharmacokinetic reporting, and safety evaluation. Translation to clinics will require standardized nose-to-brain metrics, long-term safety studies, scalable manufacturing processes, and early regulatory alignment.

Prostate cancer is the second most common cancer in men worldwide, highlighting the urgent need for effective and targeted chemotherapeutic approaches. This study reports the development and optimization of 5-fluorouracil (5-FU)-loaded poly-(lactic-co-glycolic acid)-polyethylene glycol-folic acid (PLGA-PEG-FOL) nanoparticles designed for folate receptor-mediated targeted therapy. The PLGA-PEG-FOL conjugate was synthesized via a stepwise carbodiimide coupling reaction and confirmed by FT-IR analysis. Nanoparticles were formulated via a modified emulsification-solvent evaporation method and optimized through a Box-Behnken design. The optimized formulation demonstrated a particle size of 178.47  ±  3.26 nm, a narrow polydispersity index (0.119  ±  0.008), a zeta potential of -23.4  ±  0.35 mV, a high entrapment efficiency (78.93  ±  1.05%), and sustained release of 5-FU for up to 72 h. In vitro cytotoxicity assays in PC-3 prostate cancer cells revealed a 1.6-fold reduction in the IC50 value compared with that of free 5-FU, indicating enhanced therapeutic potency. In vivo efficacy was evaluated in testosterone-induced prostate cancer in male Wistar rats. Compared with the control, treatment with 5-FU-loaded PLGA-PEG-FOL nanoparticles significantly reduced the prostate index and produced a 2.2-fold decrease in serum PSA levels and a 1.9-fold decrease in serum testosterone levels. Histopathological examination confirmed the attenuation of hyperplastic and dysplastic lesions in the nanoparticle-treated group. These findings suggest that PLGA-PEG-FOL nanoparticles are a promising targeted delivery platform for enhancing the therapeutic efficacy of 5-FU in prostate cancer treatment.

The oral administration of darifenacin hydrobromide (DBr) is associated with low bioavailability of 15–19

Empagliflozin (EMPA) is an SGLT2 inhibitor, a new class of anti-diabetic medication, indicated for treating type-2 diabetes. Its low permeability, poor solubility and bioavailability limits its use in management of diabetes. The study was aimed to formulate EMPA loaded polymeric micelles (PMs) to overcome these obstacles in oral absorption. In silico studies-molecular docking, molecular dynamic simulation (MDS), and quantum chemical calculation were employed to study the interaction of EMPA with different polymers. EMPA loaded TPGS polymeric micelles (EMPA-TPGS-PMs) were formulated by direct dissolution method and characterized in terms of surface morphology, entrapment, particle size, in vitro drug release, and in vitro cytotoxicity (HEK293 cells). In vivo pharmacokinetic and pharmacodynamic studies were also performed. The results suggested a good interaction between TPGS and EMPA with lowest binding energy compared to other polymers. Further MDS results and DFT calculations validated the stable binding of the complex hence TPGS was selected for further wet lab experiments. The EMPA-TPGS complex displayed lower value of Total energy (T.E.) than its individual components, indicating the overall stability of the complex while, the energy band gap (∆E) value lied between the two individual molecules, signifying the better electron transfer between HOMO and LUMO of the complex. Based on the solubility, entrapment and cytotoxicity studies, 5 • Molecular docking was performed to screen various polymers. • Molecular dynamics simulation and quantum chemical calculation validated molecular level interaction between Empagliflozin and TPGS. • Empagliflozin-loaded TPGS micelles exhibited nanometric size range, enhanced solubility, no cytotoxicity and controlled release. • EMPA-TPGS-PMs showed higher bioavailability and enhanced antidiabetic activity in mice models. • Developed nanocarrier could become a promising delivery system for management of diabetes.

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 - time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Rivaroxaban (RXN) finds use in the management of pulmonary embolism and deep vein thrombosis. Its poor solubility (5–7 µg/mL) and P-gp-mediated efflux from intestinal lining limits the oral application of RXN. This work assessed the impact of liquisolid compact technique in augmenting the solubility and bioavailability of RXN. PEG 400, Avicel PH 200, and Aerosil 200 were used as non-volatile liquid, carrier, and coating material, respectively, to formulate RXN liquid–solid compacts (RXN LSCs). A 32-factor factorial design was used in the optimisation to assess the impacts of factors (load factor and carrier:coating ratio) on the responses (angle of repose and Q30 min). Pre-compression parameters of RXN LSCs suggested adequate flow and compressibility. Optimisation data suggested significant influence of factors on both the responses. Optimised RXN LSC-based tablets showed a significantly higher in vitro dissolution rate than RXN API and Xarelto® tablets due to improved solubility, reduced crystallinity, greater surface area, and enhanced wetting of RXN particles. XRD, DSC, and SEM data supported RXN’s amorphization. The cytotoxicity (MTT assay) and permeation studies indicated the nontoxicity of prepared RXN LSC tablets and the role of PEG 400 in inhibiting P-gp. Pharmacokinetic study of RXN LSC-based tablets in Albino Wistar rats exhibited 2.51- and 1.66-times higher AUC in comparison to RXN API and Xarelto® tablets respectively, demonstrating that developed formulation had a greater oral bioavailability. The RXN LSC tablets showed longer bleeding times and higher rates of platelet aggregation than RXN API. Thus, RXN LSC tablets can be considered a facile, scalable technology.

Glaucoma is one of the widely prevalent ophthalmological conditions responsible for extreme clinical outcomes like loss of vision. This necessitates the need for proper therapeutic management of the condition. Although a number of treatment paradigms are being practiced by clinicians, they are marred by limited success in management. The primary reason behind the partial efficacy and success is owing to the nonadherence and insufficient concentrations at the target sites. Nanotechnology has demonstrated its competencies to alleviate the therapeutic limitations of multiple classes of drugs. Nanocarrier-based delivery of antiglaucoma agents can be leveraged to enhance the bioavailability, site-specific targeting, and controlled drug release. These benefits can ultimately translate to better therapeutic modalities to combat glaucoma. The chapter delves into the intricacies of polymeric and lipid nanocarriers for glaucoma management.

BACKGROUND:Darifenacin hydrobromide, a BCS Class II drug, is poorly bioavailable due to extensive first-pass metabolism. The present study is an attempt to investigate an alternative route of drug delivery by developing a nanometric microemulsion-based transdermal gel for the management of an overactive bladder.METHODS:Oil, surfactant, and cosurfactant were selected based on the solubility of the drug, and surfactant: cosurfactant in surfactant mixture (Smix) was selected at a 1:1 ratio as inferred from the pseudo ternary phase diagram. The D-optimal mixture design was used to optimize the o/w microemulsion wherein the globule size and zeta potential were selected as dependable variables. The prepared microemulsions were also characterized for various physico-chemical properties like transmittance, conductivity, and TEM. The optimized microemulsion was gelled using Carbopol 934 P and assessed for drug release in vitro and ex vivo, viscosity, spreadability, pH, etc.RESULTS:Drug excipient compatibility studies showed that the drug was compatible with formulation components. The optimized microemulsion showed a globule size of less than 50 nm and a high zeta potential of -20.56 mV. The ME gel could sustain the drug release for 8 hours as reflected in in vitro and ex vivo skin permeation and retention studies. The accelerated stability study showed no significant change in applied storage conditions.CONCLUSION:An effective, stable, non-invasive microemulsion gel containing darifenacin hydrobromide was developed. The achieved merits could translate into increased bioavailability and dose reduction. Further confirmatory in vivo studies on this novel formulation, which is a cost-effective & industrially scalable option, can improve the pharmacoeconomics of overactive bladder management.

The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.

Background: Rifaximin, a BCS class IV drug, possesses low bioavailability due to low solubility and low permeability attributable to P-gp efflux. The studies attempted to develop pH-sensitive rifaximin tablets based on ternary solid dispersion (TSD) for spatial and temporal drug release in colon. Materials and Methods: Rifaximin TSD was prepared using Neusilin US2 as a mesoporous carrier and Poloxamer 188 as a hydrophilic carrier and P-gp inhibitor by solvent evaporation technique employing acetone at 1:5 ratio. The TSD was assessed for P-gp inhibition using the gut sac method and Caco-2 permeability studies. The TSD was compressed into tablets and coated with pH-sensitive polymers. Coating optimization was carried out using a 32 factorial design, wherein % coating and ratio of Eudragit S100:Eudragit L100 were the independent variables and % drug release at 2 h and % drug release at 8 h were the dependent variables. Results: Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies of rifaximin TSD suggested amorphization of the drug. Gut sac studies indicated higher mucosal to serosal permeability of rifaximin from TSD. Caco-2 permeability studies demonstrated a 4.83-fold higher permeability of rifaximin from TSD (polaxamer 25% w/w and Neusilin 55% w/w of TSD) and a significant change in efflux ratio. In-vitro release studies of the coated tablets displayed controlled and site-specific release at pH of the colon. Conclusion: Effective, stable, pH-dependent rifaximin colon-targeted tablets with enhanced dissolution, permeability, and reduced P-gp efflux were developed. The achieved merits could translate into augmented bioavailability and dose reduction. Further in-vivo studies on this novel formulation, which is cost-effective and industrially scalable, can improve the pharmacoeconomics of inflammatory bowel disease management.

: Stimuli-triggered nanovectors for drug delivery enhance the clinical efficacy and decrease the toxicity by specifically conveying the drugs to the site of target with a higher specificity and efficiency. Several stimuli were regarded, but light as an exogenous stimulus tenders several benefits in clinical usage like elevated spatial and temporal control economically. A number of photochemical mechanisms have been exploited in design of phototriggered nanocarriers for biomedical applications. Light in conjugation with photosensitizers or imaging agents in nanovectors can be truly rewarding to ensure precise diagnosis, drug delivery and improve therapeutic outcomes. Nanomedicine plays a key role in enhancing therapeutic efficacy and limiting the adverse effects. The review evaluates the multiple nanocarriers such as liposomes, polymersomes, micelles, nanogels etc., which have leveraged the advantages of phototargeting via photothermal, photochemical, photo isomerization and upconversion based activation strategies for efficient drug targeting to intracellular and other regions. The significant benefits and constraints, an overview of the implementation and latest developments for the most popular and recent photoresponsive drug delivery methods are discussed to critically judge its success and limitations and delve upon the possible future perspectives in the field.

Skin cancers are among the widely prevalent forms of cancer worldwide. The increasing industrialization and accompanied environmental changes have further worsened the skin cancer statistics. The stern topical barrier although difficult to breach is a little compromised in pathologies like skin cancer. The therapeutic management of skin cancers has moved beyond chemotherapy and surgery. The quest for a magic bullet still prevails, but topical drug delivery has emerged as a perfect modality for localized self-application with minimal systemic ingress for the management of skin cancers. Advances in topical drug delivery as evidenced by the exploration of nanocarriers and newer technologies like microneedle-assisted/mediated therapeutics have revolutionized the paradigms of topical treatment. The engineered nanovectors have not only been given the liberty to experiment with a wide-array of drug carriers with very distinguishing characteristics but also endowed them with target specificity. The biologicals like nucleic acid-based approaches or skin penetrating peptide vectors are another promising area of skin cancer therapeutics which has demonstrated potential in research studies. In this review, a panoramic view is presented on the etiology, therapeutic options, and emerging drug delivery modalities for skin cancer. Nanocarriers have presented innumerable opportunities for interventions in skin cancer therapeutics. Challenge persists for the bench to bedside translation of these highly potential upcoming therapeutic strategies.

The vaginal cavity is a key part of the female reproductive system and can serve as a drug delivery site. Historically it has been utilized for local delivery, but advances in drug delivery science have explored its use systemically. Over the years, researchers have yearned for alternatives to oral and parenteral delivery as noninvasive drug delivery always has better patient compliance. The vagina presents itself as a logical option by virtue of its unique physiological attributes. Local drug administration to the vagina focuses on treating the local disorders, while systemic delivery has investigated a wide range of therapeutically active compounds. The earlier vaginal dosage forms included tablets, pessaries, creams, and gels. The upcoming newer dosage forms tend to improve the therapeutics with better control over drug delivery. Polymers have become an indispensable aid in most of the systems developed so far. Different classes of polymers have been used in vaginal drug delivery systems. This chapter focuses on the applications of these polymers in vaginal drug delivery.

Ticagrelor (TG) suffers from low peroral bioabsorption (36%) due to P-gp efflux and poor solubility (10 µg/mL). TG solid dispersion adsorbates (TG-SDAs) were formulated using an amalgamation of solid dispersion and melt adsorption techniques which were simple, economic, scalable, and solvent-free. FTIR indicated no incompatibility between drug and excipients. DSC, XRD, and SEM suggested a reduction in TG crystallinity. Q30min from TG-SUSP and TG-conventional tablets was only 2.30% and 6.59% respectively whereas TG-SDA-based tablets exhibited a significantly higher drug release of 86.47%. Caco-2 permeability studies showed 3.83-fold higher permeability of TG from TG-SDAs. TG-SDA-based tablets exhibited relative bioavailability of 748.53% and 153.43% compared to TG-SUSP and TG-conventional tablets respectively in rats. TG-SDA-based tablets were devoid of any cytotoxicity as indicated by MTT assay and exhibited better antiplatelet activity in rats. Enhanced oral bioavailability of TG-SDAs can be attributed to inhibition of P-gp efflux by PEG 4000, increased wettability, and reduced crystallinity of drug leading to improved drug solubility and dissolution. Improved bioabsorption results in a reduction of dose, cost of therapy as well as dose-related side effects. Thus, SDAs can be considered a promising and scalable approach for the improvement of dissolution rate and solubility of TG. TG-SDAs can be translated to an effective and safe dosage form, whereby its rapid onset of action promotes the prevention of heart attack, stroke, and related ill events in individuals with the acute coronary syndrome. However, scale-up, validation, and clinical-studies are necessary for confirmation of the proof-of-concept.

Nanomedicines exhibit unbelievable capability in overcoming the hurdles faced in biological applications. Carbon nanotubes (CNTs), graphene-family nanomaterials and fullerenes are a class of engineered nanoparticles that have emerged as a new option for possible use in drug/gene delivery for life-threatening diseases. Their adaptability to pharmaceutical applications has opened new vistas for biomedical applications. Successful applications of this family of engineered nanoparticles in various fields may not support their use in medicine due to inconsistent data on toxicity as well as the lack of a centralized toxicity database. Inconsistent toxicological studies and lack of mechanistic understanding have been the reasons for limited understanding of their toxicological aspects. These nanoparticles, when underivatized or pristine, are considered as safe, however less reactive. The derivatized forms or functionalization changes their chemistry significantly to modify their biological effects including toxicity. They can cause acute and long term injuries in tissues by penetration through the the blood-air barrier, blood-alveolus barrier, blood-brain barrier, and blood-placenta barrier. and by accumulating in the lung, liver, and spleen . The toxicological effects are manifested through inflammatory response, DNA damage, apoptosis, autophagy and necrosis. Other factors that largely influence the toxicity of carbon nanotubes, graphenes and fullerenes are the concentration, functionalization, dimensional and surface topographical factors. Thus, a better understanding of the toxicity profile of CNTs, graphene-family nanomaterials and fullerenes in humans, animals and the environment is of significant importance, to improve their biological safety, to facilitate their wide biological application and for the successful commercial application. The exploration of appropriate cell lines to investigate specific receptors and intracellular targets as well as chronic toxicity beyond the proof-of-concept is required.

This chapter delves into the intricacies and applications of such smart polymers in meeting drug delivery and targeting challenges. The use of polymeric material for maneuvering drug release from various dosage forms has a long history. The skin is the most formidable barrier against drug delivery but still exhibits typical characteristics which may be exploited in the design of bioresponsive systems. Researchers have explored pH-sensitive hydrogels extensively in topical drug delivery applications. Hydroxyethyl cellulose-hyaluronic acid complex hydrogels have been investigated for the transdermal delivery of Isoliquiritigenin. Thermoresponsive polymers can be of great utility in designing hydrogel systems for topical drug delivery where even self-triggering by the patient can be done. The drug delivery from smart polymers could be augmented with the use of supportive technologies like iontophoresis and use of chemical permeation enhancers. The possibility of breaching the stratum corneum barrier with ease has opened plethora of opportunities for trancutaneous delivery of large molecules, hydrophilic moieties, vaccines, etc.

Background: The objective of this study was to develop solid lipid nanoparticles (SLNs) of poorly water soluble anti-hyperlipidemic drugs-Ezetimibe in combination with Simvastatin. Methods: This study describes a 32 full factorial experimental design to optimize the formulation of drug loaded lipid nanoparticles (SLN) by the high speed homogenization technique. The independent variables amount of lipid (GMS) and amount of surfactant (Poloxamer 188) were studied at three levels and arranged in a 32 factorial design to study the influence on the response variables- particle size, % entrapment efficiency (%EE) and cumulative drug release (% CDR) at 24 h. Results: The particle size, % EE and % CDR at 24 h for the 9 batches (B1 to B9) showed a wide variation of 104.6-496.6 nm, 47.80-82.05% (Simvastatin); 48.60-84.23% (Ezetimibe) and 54.64-92.27% (Simvastatin); 43.8-97.1% (Ezetimibe), respectively. The responses of the design were analysed using Design Expert 10.0.2. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw response surface plots. From the statistical analysis of data, polynomial equations were generated. Optimized formulation showed particle size of 169.5 nm, % EE of 75.43% (Simvastatin); 79.10% (Ezetimibe) and 74.13% (Simvastatin); 77.11% (Ezetimibe) %CDR after 24 h. Thermal analysis of prepared solid lipid nanoparticles gave indication of solubilisation of drugs within lipid matrix. Conclusion: Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drugs and lipid matrix and being only dissolved in it. Electron microscope of transmission techniques indicated sphere form of prepared solid lipid nanoparticles with smooth surface with size approximately around 100 nm.

Objective: The objective of the present studies was to develop and evaluate curcumin loaded NLCs for management of childhood dermatitis by exploiting its antimicrobial and anti-infective properties and increasing its skin deposition. Methods: The screened lipidic excipients (on solubility basis) were used to formulate NLC dispersion by solvent injection technique and process variables were optimized. Central composite design was employed to study the effect of surfactant, total lipid and ratio of solid lipid to liquid lipid on dependent variables such as particle size, zeta potential, % entrapment efficiency and time for 80% drug release. Curcumin NLCs were incorporated into carbopol 934 P based gel and characterized for morphological and rheological properties, drug release, skin permeation and retention study, skin irritancy, in vitro microbial activity and stability. Results: The optimized formulations exhibited satisfactory physicochemical properties and followed Higuchi kinetic model. The NLC dispersion when incorporated into gel, was stable and nonirritating. Antimicrobial study against S. aureus showed larger zone of inhibition with developed formulation. Statistical model indicated that higher surfactant concentrations, lower lipid concentrations, reducing the solid lipid content minimized the particle size, maximized the % entrapment efficiency and optimized time for 80% drug release, while it had an inverse effect on zeta potential. The TEM of NLC dispersions elucidated its sphericity. Conclusion: The developed curcumin NLC gel exhibited potential in management of childhood dermatitis by virtue of sustained drug release, increase skin deposition and efficient antimicrobial action.

The success of drug therapy is highly dependent on route of administration, and oral route of administration is the most successful, popular, and patient friendly. However, the bioavailability of many drugs is less due to first-pass metabolism which paved a way for development of innovative drug formulations and routes of administration. Biologics and antineoplastic therapeutics are restricted to parenteral route only due to bioavailability issues in other routes of administration which often leads to off-target toxicities; therefore inhalational route for therapeutic delivery has been gaining attention recently to enhance bioavailability by taking advantage of rich blood supply of lungs. This route is used for delivering agents locally to the lungs during diseased states such as chronic obstructive pulmonary disease, asthma, or cystic fibrosis. It also acts as a portal to access blood and lymphatic systems. Nasal route has been explored since the beginning of human civilization, and Indian Ayurvedic system of medicine uses this route since long. Rapid onset of action of systemically acting products is an important advantage. The present chapter covers factors affecting absorption, drug repositioning strategies, characterization tests, and clinical trials of nasal as well as pulmonary therapeutics.