Rahul Shukla's research while affiliated with National Institute of Pharmaceutical Education and Research and other places

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Publications (153)


Cannabis and Derivatives Guide to Medical Application and Regulatory Challenges
  • Book

June 2024

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11 Reads

Rahul Shukla

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Ashish Dhir

Cannabis and its Derivatives: Guide to Medical Application and Regulatory Challenges summarizes the current state of research and clinical pharmacology of cannabis-based therapeutics, along with associated regulatory frameworks. Sections cover historical, botanical, and taxonomical platforms of cannabis, chemical derivatives of the cannabis plant, a literature review of therapeutic applications, the biological fate of cannabis and its metabolic products, pain management, neurological disorders, cancer management, interactions with other drugs, veterinary applications, and the adverse effects of Cannabis overuse in humans. The book's final section is devoted to discussions around regulatory challenges and future considerations. This is the ideal reference pharmaceutical scientists, clinicians, and academic researchers who want access to updated information on the therapeutic applications of cannabis and its derivates. Corporate researchers will also benefit from this book’s presentation of the associated regulatory environment. Key Features Explores the potential of Cannabis derivatives and medicinal properties in several medical fields Highlights the regulatory challenges around the clinical use and research of Cannabis Covers applications to conditions like cancer, neurological disorders, pain management, and interactions with other drugs

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Manoeuvring the innovative drug delivery systems for veterinary therapeutics: Present day demand

June 2024

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37 Reads

European Polymer Journal

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[...]

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Rahul Shukla

Animals in the present day confront a range of difficulties when it comes to receiving adequate medical care. Most of these challenges arise from the constraints of traditional methods for administering drugs and the forms in which dosages are provided. Furthermore, animals commonly face compliance problems, hindering consistent and precise medication administration. This is worsened by the absence of suitable dosage forms and the lack of control over drug release and timing. All of these issues demand advanced drug delivery strategies that provide safe, effective, and compliant treatment with efficacy. Recently, controlled drug delivery systems (CDDS) have garnered significant attention in the field of veterinary medicine. Precisely, CDDS employing polymers, lipids, and other biomaterials can achieve controlled release of veterinary drugs, prolonging the therapeutic effects, and thereby reducing dosing frequency. In this regard, the present review provides a concise overview of various CDDS and polymer-engineered technologies designed for veterinary medicines. Additionally, it thoroughly examines diverse administration routes for veterinary formulations, encompassing formulation design considerations, challenges, and potential industrial opportunities. Lastly, it delves into the significance of nanotechnology in veterinary medicines and provides a summary of regulatory perspectives in this field


Therapeutic Potential of Nanocrystals for Targeting Lymphoid Carcinoma

May 2024

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10 Reads

Globally, cancer ranks second for mortality rate with the mark of >ten million deaths in 2020 only. Cancer is characterized by the transmutation of normal healthy cells to abnormal cancerous cells in a multistage tumor progression. Generally, cancer is categorized as malignant (or metastatic) and benign. In metastatic embedment, lymphatics are the favorable site for carcinogenic foreign invaders. The progression of lymphatic cancer causes uncontrolled growth of all the immune cells which ensures infection of almost every organ. However, in normal individuals, lymphatics are regarded as a prominent framework for host defense with the major components of helper T-cells and B cells. Currently, available treatment modalities include painful procedures of surgical interventions, chemotherapy in combination with immunotherapy, and radiation therapy. These traditional treatments encounter various limitations which affect the socioeconomic status of a patient and their family wards. However, promising pharmaceutical nanoengineered approaches change the face of treatment and keep the pace in the patient’s recovery when compared with conventional treatment. From all the nanotechnological approaches, nanocrystal is regarded as a smart nanosized carrier as it offers advantages like targeting precision, high drug loading, devoid of organic solvents or solubilizing agents, and ease of entry within the lymphatic system via leaky tumor vasculature. Recent advancements in multifunctional nanocrystal have shown the potential of nanocrystal as a versatile delivery vehicle for lymphatic targeting with anticancer therapeutics. In this chapter, we will describe lymphatic cancer development, the need for amalgamation of nanotechnology with anticancer therapeutics, nanocrystals feasibility in lymphatic cancer targeting,



(A) FTIR spectrum of drug-excipient compatibility study of Donepezil, Pine oil, Egg lecithin, Cholesterol, Mannitol, Physical mixture and formulation; (B) DSC thermograms of Donepezil, Cholesterol, Egg lecithin, physical mixture and formulation
SEM imaging of (A) Pine oil and Donepezil loaded liposomes and (B) Donepezil loaded liposomes
PXRD pattern of Pine oil and Donepezil loaded liposomes, Donepezil, Physical mixture (Egg lecithin, Cholesterol, Mannitol)
In vitro release study of Donepezil drug and Pine oil-Donepezil loaded liposomes
Images of goat nasal mucosa depicting histological characteristics when treated with (A) Phosphate buffer saline 6.4; (B) Isopropyl alcohol; (C) Blank liposomal formulation and (D) Donepezil and Pine oil loaded liposomes

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Optimization, Characterization and In-Vitro Cellular Uptake of Donepezil-Loaded NanoCrystVesicles
  • Article
  • Publisher preview available

April 2024

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72 Reads

Journal of Cluster Science

The prevalence of Alzheimer's disease (AD) in developed and developing nations is increasing day by day. The monotherapy doesn't fit best for AD due to chronic treatment. This work aimed to prepare the liposomes coloaded with Donepezil and pine oil intended for adjuvant effect. Pine oil was selected due to its amyloid disaggregation and AChE inhibition property. The thin film hydration method with sonication was selected to formulate ultra-small-sized unilamellar vesicles. Apart from this formulated vesicle were subject to particle size, morphological, release, nasal ciliotoxicity and cellular uptake studies. The PDI, particle size, and zeta potential of the final egg lecithin-based liposome were found to be 0.19, 129 nm, and -27.5 mV, respectively, stable at 4° and 25°C. SEM microscopy of oil-loaded liposomes exhibits a crystalline cubic shape and is compared with alone drug-loaded liposomes that are spherical. AChE inhibition activity was found to be higher in combination when compared with others. The prepared liposomes were safe when studied for nasal ciliotoxicity studies and rapid uptake by C6 cells with complete internalization. This study demonstrated the development and potential of the vesicular system that carries valuable characteristics and overcomes patient compliance concerns that prove to be novel therapeutics for managing AD. Graphical Abstract

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Microneedles along with conventional therapies: An in-depth observational review in alopecia areata treatment

April 2024

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43 Reads

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1 Citation

Journal of Drug Delivery Science and Technology

Alopecia areata (AA) is an emanating autoimmune disorder marked by short-term, non-scarring loss of hair in distinct patches or of the entire scalp. The transdermal drug delivery system (TDDS) is used to give drugs via transdermal patches, gels, lotions, and ointments. This approach provides better bioavailability and allows for a minimally invasive regulated release of pharmaceuticals over a longer period with fewer changes in peak plasma concentrations. It also has downsides since the stratum corneum (SC) layer, the outermost epidermal barrier, prevents large molecules from reaching this layer. This review looks at substantial research conducted on microneedles (MNs) as a potential option for the transdermal administration of drugs in addition to the expanding demand for non-invasive and patient-compatible medication administration strategies. MNs provide superior therapeutic effects than typical TDDS because they significantly increase the effectiveness of transdermal administration by bypassing the SC barrier. It also provides synergistic action with the drug by inflicting small localized wounds on the skin, which triggers the expulsion of numerous growth factors (fibroblast, platelet-derived, and transforming growth factors), enhancing collagen, elastin production and allows for spatiotemporally regulated medication release in the epidermal layers. This review comprises the epidemiology, pathophysiology, hair growth cycle, MN drug delivery strategies, and successful preclinical and clinical cases of MN combining drug treatment for the treatment of AA.


Structural representation of the blood–brain barrier and its interface. The BBB is a prime checkpoint which selectively allows permeation of essential molecules. Biomacromolecules can be transported across the BBB via various pathways such as receptor-mediated trans-endocytosis, active targeting, passive diffusion and few other allied mechanisms. The brain microvasculature interface is made of endothelial cells, astrocytic projection and pericyte network
Nicotinic acid cycle. Nicotinic acid receptor is as an essential receptor for successful uptake and utilization of GABA and glutamate. Maintenance of these two neurotransmitters within neuronal network is quintessential as dyshomeostasis within these two neurotransmitters can lead to development of neurological challenges
Glucose utilization within glucose transporter and neuron. Glucose is essential for maintaining homeostasis within the brain and in energy production of peripheral organs. Glucose mainly uptake via electron transport chain further undergoes glycolysis process within neuron and forms pyruvate molecules which further utilized via mitochondria and generates ATP molecules
Transferrin-targeted drug transcytosis. Transferrin is a leading and most exploited receptor for strategic endocytosis of drug molecules. Ligand-conjugated or transferrin-coated nanocarriers assimilated via the receptor bridges and further uptake via early endosome and thereby release the drug content within cellular vesicle
Depiction of neurological sequelae and its impact on BBB integrity. Ischaemic stroke, demyelination and hypoxia are the common neurological challenges that alter the permeability of the BBB or often disrupt its integrity. All these neurological challenges are resultant of involvement of proinflammatory mediators and hyperactivation of immune system. BBB damage is usually accompanied with damage in tight intracellular cells, hyperactivation of glial cells and altered permeability quotient via paracellular or transcellular pathway
Receptor-Assisted Nanotherapeutics for Overcoming the Blood–Brain Barrier

Molecular Neurobiology

Blood–brain barrier (BBB) is a distinguishing checkpoint that segregates peripheral organs from neural compartment. It protects the central nervous system from harmful ambush of antigens and pathogens. Owing to such explicit selectivity, the BBB hinders passage of various neuroprotective drug molecules that escalates into poor attainability of neuroprotective agents towards the brain. However, few molecules can surpass the BBB and gain access in the brain parenchyma by exploiting surface transporters and receptors. For successful development of brain-targeted therapy, understanding of BBB transporters and receptors is crucial. This review focuses on the transporter and receptor–based mechanistic pathway that can be manoeuvred for better comprehension of reciprocity of receptors and nanotechnological vehicle delivery. Nanotechnology has emerged as one of the expedient noninvasive approaches for brain targeting via manipulating the hurdle of the BBB. Various nanovehicles are being reported for brain-targeted delivery such as nanoparticles, nanocrystals, nanoemulsion, nanolipid carriers, liposomes and other nanovesicles. Nanotechnology-aided brain targeting can be a strategic approach to circumvent the BBB without altering the inherent nature of the BBB.


Harnessing the potential of nanoengineered siRNAs carriers for target responsive glioma therapy: Recent progress and future opportunities

March 2024

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101 Reads

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1 Citation

International Journal of Biological Macromolecules

Past scientific testimonials in the field of glioma research, the deadliest tumor among all brain cancer types with the life span of 10-15 months after diagnosis is considered as glioblastoma multiforme (GBM). Even though the availability of treatment options such as chemotherapy, radiotherapy, and surgery, are unable to completely cure GBM due to tumor microenvironment complexity, intrinsic cellular signalling, and genetic mutations which are involved in chemoresistance. The blood-brain barrier is accountable for restricting drugs entry at the tumor location and related biological challenges like endocytic degradation, short systemic circulation, and insufficient cellular penetration lead to tumor aggression and progression. The above stated challenges can be better mitigated by small interfering RNAs (siRNA) by knockdown genes responsible for tumor progression and resistance. However, siRNA encounters with challenges like inefficient cellular transfection, short circulation time, endogenous degradation, and off-target effects. The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment.


Major penetration pathways of skin. Main pathways for drug transportation across skin are intracellular pathway, intercellular pathway, and appendageal pathway. Understanding of layers of skin and their lipidic composition can improve the therapeutic targetability.[³⁰]
Method of preparation of nanocrystals. Formulation method for development of nanocrystals is broadly classified as top‐down approach and bottom‐up approach along with combinatorial approach.[²³]
Mechanism of Nanocrystal Penetration in skin. Nanocrystals mainly penetrated in deep skin layers via a) hair follicular targeting b) cellular uptake c) adhesion d) concentration gradient. These pathways commonly offer prolong residence interval, occlusive effect, and adhesion on skin layer. Nanocrystal owing to its saturation solubility and stability ensures successful cargo delivery.[²]
Nanocrystals are widely explored for various skin disorders ranging from hyperpigmentation, cutaneous candidiasis, diabetic foot ulcer, rosacea, acne skin carcinoma, and inflammatory reactions. Topical nanocrystals formulation showed site‐directed treatment, prolong contact time, ease of application, and patient acceptability under various lituerature sources.[²⁰]
Nanocrystals: A Multifaceted Regimen for Dermatological Ailments
Particle & Particle Systems Characterization

Particle & Particle Systems Characterization

Skin disorders are the most common apprehension worldwide among different regions of the world. Topical route of administration offers benefits over other routes such as avoidance of first‐pass metabolism, low dose, longer residence time, and absence of off‐target delivery. Skin serves as a mechanical barrier for therapeutic delivery with selectively permeable essential molecules. Considering the structural complexity of skin, delivery of therapeutics at targeted site requires sophisticated method such as nanotechnology‐assisted therapeutic delivery. The roadmap for combinatorial approach of nanotechnology and skin therapeutics has proven significant in clinical and marketed products. Currently, various pharmaceutical aids such as nanocrystal (NCs), nanoparticles, nanoemulsion, nano‐micelles, nano lipidic carriers, and hybrid nanocarriers are currently in market. Among all the other nanocarriers, nanocrystal offers precedence over other nanocarriers due to its facile method of preparation, reproducibility, low excipient concentration, and high therapeutic loading capacity. The recent literature data suggest the breakthrough evolution of NCs in topical therapeutic delivery. The outcome of these interventions envisages the applicability of NCs for delivering molecules with compromised physicochemical characteristics such as solubility, stability, toxicity, and bioavailability concerns.


Drug Nanocrystals: A Delivery Channel for Antiviral Therapies

February 2024

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36 Reads

AAPS PharmSciTech

Viral infections represent a significant threat to global health due to their highly communicable and potentially lethal nature. Conventional antiviral interventions encounter challenges such as drug resistance, tolerability issues, specificity concerns, high costs, side effects, and the constant mutation of viral proteins. Consequently, the exploration of alternative approaches is imperative. Therefore, nanotechnology-embedded drugs excelled as a novel approach purporting severe life-threatening viral disease. Integrating nanomaterials and nanoparticles enables ensuring precise drug targeting, improved drug delivery, and fostered pharmacokinetic properties. Notably, nanocrystals (NCs) stand out as one of the most promising nanoformula-tions, offering remarkable characteristics in terms of physicochemical properties (higher drug loading, improved solubility, and drug retention), pharmacokinetics (enhanced bioavailability, dose reduction), and optical properties (light absorptiv-ity, photoluminescence). These attributes make NCs effective in diagnosing and ameliorating viral infections. This review comprises the prevalence, pathophysiology, and resistance of viral infections along with emphasizing on failure of current antivirals in the management of the diseases. Moreover, the review also highlights the role of NCs in various viral infections in mitigating, diagnosing, and other NC-based strategies combating viral infections. In vitro, in vivo, and clinical studies evident for the effectiveness of NCs against viral pathogens are also discussed.


Citations (65)


... With diameters ranging from 50 to 1000 nm, nanocarriers have the distinctive quality of having a greater surface area-to-volume ratio. This quality improves the medications' pharmacokinetic characteristics and the way they are distributed throughout the body [25]. Consequently, nanocarriers, particularly NCs, are emerging as flexible alternatives for delivering insufficiently water-soluble active chemicals, despite issues with drug loading capacity and physicochemical qualities. ...

Reference:

Drug Nanocrystals: A Delivery Channel for Antiviral Therapies
Multifunctional nanocrystals for liver cancer
  • Citing Chapter
  • January 2024

... Derived from plant sources, these nanovesicles align with the growing trend towards sustainable and eco-friendly cosmetic formulations. Their ability to encapsulate and deliver essential oils in a controlled manner addresses volatility and solubility issues, providing a foundation for sophisticated dermocosmetic delivery systems [34][35][36]. ...

Nanocarriers for the Delivery of Cosmeceuticals
  • Citing Chapter
  • January 2024

... The IN NPs showed significant brain targeting in rats with the % DTE and % DTP values of the IN NP reported to be 129.81 % and 23%, respectively [112]. [170] Note: Emul SE = Emulsification solvent evaporation; Nano P = Nanoprecipitation; CE = Conjugation efficiency. ...

Combining donepezil and memantine via mannosylated PLGA nanoparticles for intranasal delivery: Characterization and preclinical studies
  • Citing Article
  • October 2023

Biomaterials Advances

... Diseases, such as cancer, where targeted delivery to tumor sites is essential for effective treatment while reducing systemic toxicity, stand to benefit immensely. Additionally, treatments for neurological disorders like Alzheimer's or Parkinson's disease could benefit from magnetomorph's approach, as it allows for the delivery of drugs directly to specific areas of the brain, bypassing the blood-brain barrier [13]. Moreover, conditions involving localized inflammation, such as rheumatoid arthritis or inflammatory bowel diseases, could be improved with targeted drug delivery, as it enables precise administration to inflamed tissues while sparing healthy ones [14]. ...

Nanovesicular-Mediated Intranasal Drug Therapy for Neurodegenerative Disease
  • Citing Article
  • September 2023

AAPS PharmSciTech

... Levels of pro-inflammatory mediators were reduced in NC-treated mice suggesting significant anti-TB activity. The nano-formulation proved to ameliorate pathogenic conditions in an experimental animal while ensuring safety and efficacy of the drug [84]. ...

Clofazimine nanoclusters show high efficacy in experimental TB with amelioration in paradoxical lung inflammation
  • Citing Article
  • August 2023

Biomaterials Advances

... Vincristine, a microtubule polymerisation inhibitor, is a broad-spectrum cytotoxic agent that is widely employed in oncology [4]. It has also been reported to act as an efficacious treatment against skeletal metastases from medulloblastoma [5]. ...

Vincristine-based nanoformulations: a preclinical and clinical studies overview

Drug Delivery and Translational Research

... The supernatant was subjected to filtration using a 0.22-µm syringe filter. It was then diluted with methanol and analysed using a UV-visible spectrometer at a wavelength of 272 nm, which corresponds to the maximum absorbance [20]. ...

Simultaneous Intranasal Codelivery of Donepezil and Memantine in a Nanocolloidal Carrier: Optimization, Pharmacokinetics, and Pharmacodynamics Studies
  • Citing Article
  • July 2023

Molecular Pharmaceutics

... The poly (vinyl alcohol) (PVA) synthetic polymer protects the RNAs against nuclease degradation and in its cationic nature, it is considered a valuable vehicle for gene RNA delivery. Polyamidoamine (PLL) is a tertiary amine branched synthetic polymer and is preferred for gene delivery concerning the complex site of delivery like glioblastoma and inner ear [135]. The Poly(lactic-co-glycolide) is used as RNA delivery and it is made up of a combination of glycolic acid and lactic acid Therefore, the cationic polymers are selected as RNA delivery agents since they offer the capability to condense the negatively charged RNAs and protect them from nuclease degradation [136]. ...

Vitamin E Modified Polyamidoamine Dendrimer for Piperine Delivery to Alleviate Aβ1-42 Induced Neurotoxicity in Balb/c Mice Model
  • Citing Article
  • June 2023

Journal of Biomaterials Science Polymer Edition

... Moreover, the tailored design of lipoplexes permits customization according to specific therapeutic requirements, encompassing considerations such as payload stability, tissue targeting, and immunogenicity modulation [11]. In the context of disease management, lipoplexes offer a promising avenue across a spectrum of pathologies, including genetic disorders [12], infectious diseases [13,14], and cancer [3,15]. Their ability to traverse biological barriers, penetrate target cells, and selectively modulate gene expression underpins their utility in gene therapy, RNA interference, and molecular diagnostics. ...

Hyaluronic acid-functionalized lipoplexes and polyplexes as emerging nanocarriers for receptor-targeted cancer therapy
  • Citing Article
  • June 2023

Environmental Research

... (200 • C), and minimal dose (daily dose 10 mg) can penetrate the skin easily [21]. In response to the rising desire for non-invasive and patient-friendly medication delivery techniques, extensive study has been done on MNs as a potential choice for transdermal administration of drugs [22,127]. ...

Therapeutic potential of microneedles based delivery systems for the management of atopic dermatitis
  • Citing Article
  • May 2023

Journal of Drug Delivery Science and Technology